The crosstalk between brain and periphery: Implications for brain health and disease
Neuropharmacology. 2021 Jul 28:108728. doi: 10.1016/j.neuropharm.2021.108728. Online ahead of print.ABSTRACTMounting evidence indicates that signaling molecules identified primarily in the peripheral circulation can affect cognitive function in physiological and pathological conditions, including in the development of several neurological diseases. However, considering the properties of the vascular blood-brain barrier (BBB), circulating lipophobic molecules would not be expected to cross this vascular structure. Thus, if and how peripheral lipophobic molecules, such as hormones and cytokines, reach the brain to exert thei...
Source: Neuropharmacology - July 31, 2021 Category: Drugs & Pharmacology Authors: Rafaella A Gon çalves Fernanda G De Felice Source Type: research

Optimising the energetic cost of the glutamatergic synapse
This article will review how much of the energetic cost of the brain reflects the activity of glutamatergic synapses, consider the relative amount of energy used pre- and postsynaptically, outline how evolution has energetically optimised synapse function by adjusting the presynaptic release probability and the postsynaptic number of glutamate receptors, and speculate on how energy use by synapses may be sensed and adjusted.PMID:34314736 | DOI:10.1016/j.neuropharm.2021.108727 (Source: Neuropharmacology)
Source: Neuropharmacology - July 27, 2021 Category: Drugs & Pharmacology Authors: Jonathan Lezmy Julia J Harris David Attwell Source Type: research

Optimising the energetic cost of the glutamatergic synapse
This article will review how much of the energetic cost of the brain reflects the activity of glutamatergic synapses, consider the relative amount of energy used pre- and postsynaptically, outline how evolution has energetically optimised synapse function by adjusting the presynaptic release probability and the postsynaptic number of glutamate receptors, and speculate on how energy use by synapses may be sensed and adjusted.PMID:34314736 | DOI:10.1016/j.neuropharm.2021.108727 (Source: Neuropharmacology)
Source: Neuropharmacology - July 27, 2021 Category: Drugs & Pharmacology Authors: Jonathan Lezmy Julia J Harris David Attwell Source Type: research

Optimising the energetic cost of the glutamatergic synapse
This article will review how much of the energetic cost of the brain reflects the activity of glutamatergic synapses, consider the relative amount of energy used pre- and postsynaptically, outline how evolution has energetically optimised synapse function by adjusting the presynaptic release probability and the postsynaptic number of glutamate receptors, and speculate on how energy use by synapses may be sensed and adjusted.PMID:34314736 | DOI:10.1016/j.neuropharm.2021.108727 (Source: Neuropharmacology)
Source: Neuropharmacology - July 27, 2021 Category: Drugs & Pharmacology Authors: Jonathan Lezmy Julia J Harris David Attwell Source Type: research

Optimising the energetic cost of the glutamatergic synapse
This article will review how much of the energetic cost of the brain reflects the activity of glutamatergic synapses, consider the relative amount of energy used pre- and postsynaptically, outline how evolution has energetically optimised synapse function by adjusting the presynaptic release probability and the postsynaptic number of glutamate receptors, and speculate on how energy use by synapses may be sensed and adjusted.PMID:34314736 | DOI:10.1016/j.neuropharm.2021.108727 (Source: Neuropharmacology)
Source: Neuropharmacology - July 27, 2021 Category: Drugs & Pharmacology Authors: Jonathan Lezmy Julia J Harris David Attwell Source Type: research

Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy
Neuropharmacology. 2021 Jul 22:108726. doi: 10.1016/j.neuropharm.2021.108726. Online ahead of print.ABSTRACTNeonatal rat sciatic nerve crush mimics obstetric axonotmesis, leading to extensive loss of motor and sensory neurons. The present study aimed to investigate the neuroprotective potential of cannabidiol (CBD) and the role of cannabinoid receptors after sciatic nerve crush in neonatal rats. For that, two-day-old Wistar rats were used, organized into the following experimental groups: sciatic nerve crush plus CBD treatment (CBD), crush plus vehicle treatment (VE), crush + CBD + AM251 treatment (AM251 - CB1 inverse agon...
Source: Neuropharmacology - July 25, 2021 Category: Drugs & Pharmacology Authors: Matheus Perez Luciana Politti Cartarozzi Gabriela Bortolan ça Chiarotto Francisco Silveira Guimar ães Alexandre Leite Rodrigues de Oliveira Source Type: research

Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy
Neuropharmacology. 2021 Jul 22:108726. doi: 10.1016/j.neuropharm.2021.108726. Online ahead of print.ABSTRACTNeonatal rat sciatic nerve crush mimics obstetric axonotmesis, leading to extensive loss of motor and sensory neurons. The present study aimed to investigate the neuroprotective potential of cannabidiol (CBD) and the role of cannabinoid receptors after sciatic nerve crush in neonatal rats. For that, two-day-old Wistar rats were used, organized into the following experimental groups: sciatic nerve crush plus CBD treatment (CBD), crush plus vehicle treatment (VE), crush + CBD + AM251 treatment (AM251 - CB1 inverse agon...
Source: Neuropharmacology - July 25, 2021 Category: Drugs & Pharmacology Authors: Matheus Perez Luciana Politti Cartarozzi Gabriela Bortolan ça Chiarotto Francisco Silveira Guimar ães Alexandre Leite Rodrigues de Oliveira Source Type: research

Sustained treatment with an α5 GABA A receptor negative allosteric modulator delays excitatory circuit development while maintaining GABAergic neurotransmission
Neuropharmacology. 2021 Jul 17:108724. doi: 10.1016/j.neuropharm.2021.108724. Online ahead of print.ABSTRACTα5 subunit GABA type A receptor (GABAAR) preferring negative allosteric modulators (NAMs) are cognitive enhancers with antidepressant-like effects. α5-NAM success in treating mouse models of neurodevelopmental disorders with excessive inhibition have led to Phase 2 clinical trials for Down syndrome. Despite in vivo efficacy, no study has examined the effects of continued α5-NAM treatment on inhibitory and excitatory synapse plasticity to identify mechanisms of action. Here we used L-655,708, an imid...
Source: Neuropharmacology - July 20, 2021 Category: Drugs & Pharmacology Authors: Jessica L Nuwer Megan L Brady Nadya V Povysheva Amanda Coyne Tija C Jacob Source Type: research

Sustained treatment with an α5 GABA A receptor negative allosteric modulator delays excitatory circuit development while maintaining GABAergic neurotransmission
Neuropharmacology. 2021 Jul 17:108724. doi: 10.1016/j.neuropharm.2021.108724. Online ahead of print.ABSTRACTα5 subunit GABA type A receptor (GABAAR) preferring negative allosteric modulators (NAMs) are cognitive enhancers with antidepressant-like effects. α5-NAM success in treating mouse models of neurodevelopmental disorders with excessive inhibition have led to Phase 2 clinical trials for Down syndrome. Despite in vivo efficacy, no study has examined the effects of continued α5-NAM treatment on inhibitory and excitatory synapse plasticity to identify mechanisms of action. Here we used L-655,708, an imid...
Source: Neuropharmacology - July 20, 2021 Category: Drugs & Pharmacology Authors: Jessica L Nuwer Megan L Brady Nadya V Povysheva Amanda Coyne Tija C Jacob Source Type: research

Sustained treatment with an α5 GABA A receptor negative allosteric modulator delays excitatory circuit development while maintaining GABAergic neurotransmission
Neuropharmacology. 2021 Jul 17:108724. doi: 10.1016/j.neuropharm.2021.108724. Online ahead of print.ABSTRACTα5 subunit GABA type A receptor (GABAAR) preferring negative allosteric modulators (NAMs) are cognitive enhancers with antidepressant-like effects. α5-NAM success in treating mouse models of neurodevelopmental disorders with excessive inhibition have led to Phase 2 clinical trials for Down syndrome. Despite in vivo efficacy, no study has examined the effects of continued α5-NAM treatment on inhibitory and excitatory synapse plasticity to identify mechanisms of action. Here we used L-655,708, an imid...
Source: Neuropharmacology - July 20, 2021 Category: Drugs & Pharmacology Authors: Jessica L Nuwer Megan L Brady Nadya V Povysheva Amanda Coyne Tija C Jacob Source Type: research

Sustained treatment with an α5 GABA A receptor negative allosteric modulator delays excitatory circuit development while maintaining GABAergic neurotransmission
Neuropharmacology. 2021 Jul 17:108724. doi: 10.1016/j.neuropharm.2021.108724. Online ahead of print.ABSTRACTα5 subunit GABA type A receptor (GABAAR) preferring negative allosteric modulators (NAMs) are cognitive enhancers with antidepressant-like effects. α5-NAM success in treating mouse models of neurodevelopmental disorders with excessive inhibition have led to Phase 2 clinical trials for Down syndrome. Despite in vivo efficacy, no study has examined the effects of continued α5-NAM treatment on inhibitory and excitatory synapse plasticity to identify mechanisms of action. Here we used L-655,708, an imid...
Source: Neuropharmacology - July 20, 2021 Category: Drugs & Pharmacology Authors: Jessica L Nuwer Megan L Brady Nadya V Povysheva Amanda Coyne Tija C Jacob Source Type: research

Regulation of AMPAR expression by microRNAs
Neuropharmacology. 2021 Jul 15:108723. doi: 10.1016/j.neuropharm.2021.108723. Online ahead of print.ABSTRACTAMPA receptors (AMPARs) are the major excitatory neurotransmitter receptor in the brain, and their expression at synapses is a critical determinant of synaptic transmission and therefore brain function. Synaptic plasticity involves increases or decreases in synaptic strength, caused by changes in the number or subunit-specific subtype of AMPARs expressed at synapses, and resulting in modifications of functional connectivity of neuronal circuits, a process which is thought to underpin learning and the formation or los...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Jonathan G Hanley Source Type: research

Interactions between the microbiota and enteric nervous system during gut-brain disorders
The objective of this review is to describe recent scientific elements that explore the communication between gut microbiota and the brain by focusing our interest on the enteric nervous system (ENS) as an intermediate partner. The ENS, which is known as the "second brain", could be under the direct or indirect influence of the gut microbiota and its released factors (short-chain fatty acids, neurotransmitters, gaseous factors, etc.). Thus, in addition to their actions on tissue (adipose tissue, liver, brain, etc.), microbes can have an impact on local ENS activity. This potential modification of ENS function has...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Steven Fried Eve Wemelle Patrice D Cani Claude Knauf Source Type: research

Cannabidiol effectively reverses mechanical and thermal allodynia, hyperalgesia, and anxious behaviors in a neuropathic pain model: Possible role of CB1 and TRPV1 receptors
This study presents a dose-response curve to understand better the effects of low doses (3 mg/kg) on CBD's antiallodynic and anxiolytic effects. Also, low doses of CBD were able to (1) reverse mechanical and thermal allodynia (cold) and hyperalgesia, (2) reverse anxious behaviors (reduction of the % of grooming and freezing time, and increase of the % of center time in the OFT) induced by chronic pain. The peripheral neuropathy promoted the increase in the expression of CB1 and TRPV1 receptors in the anterior cingulate cortex (ACC), anterior insular cortex (AIC), basolateral amygdala (BLA), dorsal hippocampus (DH), and ven...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Gleice K Silva-Cardoso Willian Lazarini-Lopes Jaime E Hallak Jos é A Crippa Antonio W Zuardi Norberto Garcia-Cairasco Christie R A Leite-Panissi Source Type: research

GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases
Neuropharmacology. 2021 Jul 15:108708. doi: 10.1016/j.neuropharm.2021.108708. Online ahead of print.ABSTRACTSynaptic transmission is one of the fundamental processes that all brain functions are based on. Changes in the strength of synaptic transmission among neurons are crucial for information processing in the central nervous system. The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of ionotropic glutamate receptors (AMPARs) mediate the majority of the fast excitatory synaptic transmission in the mammalian brain. Rapid trafficking of AMPARs in and out of the postsynaptic membrane is proposed to be a ...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Yuan Ge Yu Tian Wang Source Type: research

Metabotropic actions of kainate receptors modulating glutamate release
Neuropharmacology. 2021 Jul 15:108696. doi: 10.1016/j.neuropharm.2021.108696. Online ahead of print.ABSTRACTPresynaptic kainate (KA) receptors (KARs) modulate GABA and glutamate release in the central nervous system of mammals. While some of the actions of KARs are ionotropic, metabotropic actions for these receptors have also been seen to modulate both GABA and glutamate release. In general, presynaptic KARs modulate glutamate release through their metabotropic actions in a biphasic manner, with low KA concentrations producing an increase in glutamate release and higher concentrations of KA driving weaker release of this ...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Rafael Falc ón-Moya Antonio Rodr íguez-Moreno Source Type: research

Reduced neuroinflammation and enhanced neurogenesis following chronic agomelatine treatment in rats undergoing chronic constant light
Neuropharmacology. 2021 Jul 15:108706. doi: 10.1016/j.neuropharm.2021.108706. Online ahead of print.ABSTRACTExperimental studies have revealed the involvement of neuroinflammation mediated by activated microglia in the pathophysiology of depression, suggesting a novel target for treatment. The atypical antidepressant Agomelatine (Ago) has an advantage compared to the classical antidepressants due to its chronobiotic activity and unique pharmacological profile as a selective agonist at the melatonin receptors and an antagonist at the 5HT2C receptors. We have recently revealed that Ago can exert a potent antidepressant effec...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Dimitrinka Atanasova Nikolai Lazarov Dimo S Stoyanov Radoslav H Spassov Anton B Tonchev Jana Tchekalarova Source Type: research

Regulation of AMPAR expression by microRNAs
Neuropharmacology. 2021 Jul 15:108723. doi: 10.1016/j.neuropharm.2021.108723. Online ahead of print.ABSTRACTAMPA receptors (AMPARs) are the major excitatory neurotransmitter receptor in the brain, and their expression at synapses is a critical determinant of synaptic transmission and therefore brain function. Synaptic plasticity involves increases or decreases in synaptic strength, caused by changes in the number or subunit-specific subtype of AMPARs expressed at synapses, and resulting in modifications of functional connectivity of neuronal circuits, a process which is thought to underpin learning and the formation or los...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Jonathan G Hanley Source Type: research

Interactions between the microbiota and enteric nervous system during gut-brain disorders
The objective of this review is to describe recent scientific elements that explore the communication between gut microbiota and the brain by focusing our interest on the enteric nervous system (ENS) as an intermediate partner. The ENS, which is known as the "second brain", could be under the direct or indirect influence of the gut microbiota and its released factors (short-chain fatty acids, neurotransmitters, gaseous factors, etc.). Thus, in addition to their actions on tissue (adipose tissue, liver, brain, etc.), microbes can have an impact on local ENS activity. This potential modification of ENS function has...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Steven Fried Eve Wemelle Patrice D Cani Claude Knauf Source Type: research

Cannabidiol effectively reverses mechanical and thermal allodynia, hyperalgesia, and anxious behaviors in a neuropathic pain model: Possible role of CB1 and TRPV1 receptors
This study presents a dose-response curve to understand better the effects of low doses (3 mg/kg) on CBD's antiallodynic and anxiolytic effects. Also, low doses of CBD were able to (1) reverse mechanical and thermal allodynia (cold) and hyperalgesia, (2) reverse anxious behaviors (reduction of the % of grooming and freezing time, and increase of the % of center time in the OFT) induced by chronic pain. The peripheral neuropathy promoted the increase in the expression of CB1 and TRPV1 receptors in the anterior cingulate cortex (ACC), anterior insular cortex (AIC), basolateral amygdala (BLA), dorsal hippocampus (DH), and ven...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Gleice K Silva-Cardoso Willian Lazarini-Lopes Jaime E Hallak Jos é A Crippa Antonio W Zuardi Norberto Garcia-Cairasco Christie R A Leite-Panissi Source Type: research

GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases
Neuropharmacology. 2021 Jul 15:108708. doi: 10.1016/j.neuropharm.2021.108708. Online ahead of print.ABSTRACTSynaptic transmission is one of the fundamental processes that all brain functions are based on. Changes in the strength of synaptic transmission among neurons are crucial for information processing in the central nervous system. The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of ionotropic glutamate receptors (AMPARs) mediate the majority of the fast excitatory synaptic transmission in the mammalian brain. Rapid trafficking of AMPARs in and out of the postsynaptic membrane is proposed to be a ...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Yuan Ge Yu Tian Wang Source Type: research

Metabotropic actions of kainate receptors modulating glutamate release
Neuropharmacology. 2021 Jul 15:108696. doi: 10.1016/j.neuropharm.2021.108696. Online ahead of print.ABSTRACTPresynaptic kainate (KA) receptors (KARs) modulate GABA and glutamate release in the central nervous system of mammals. While some of the actions of KARs are ionotropic, metabotropic actions for these receptors have also been seen to modulate both GABA and glutamate release. In general, presynaptic KARs modulate glutamate release through their metabotropic actions in a biphasic manner, with low KA concentrations producing an increase in glutamate release and higher concentrations of KA driving weaker release of this ...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Rafael Falc ón-Moya Antonio Rodr íguez-Moreno Source Type: research

Reduced neuroinflammation and enhanced neurogenesis following chronic agomelatine treatment in rats undergoing chronic constant light
Neuropharmacology. 2021 Jul 15:108706. doi: 10.1016/j.neuropharm.2021.108706. Online ahead of print.ABSTRACTExperimental studies have revealed the involvement of neuroinflammation mediated by activated microglia in the pathophysiology of depression, suggesting a novel target for treatment. The atypical antidepressant Agomelatine (Ago) has an advantage compared to the classical antidepressants due to its chronobiotic activity and unique pharmacological profile as a selective agonist at the melatonin receptors and an antagonist at the 5HT2C receptors. We have recently revealed that Ago can exert a potent antidepressant effec...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Dimitrinka Atanasova Nikolai Lazarov Dimo S Stoyanov Radoslav H Spassov Anton B Tonchev Jana Tchekalarova Source Type: research

Regulation of AMPAR expression by microRNAs
Neuropharmacology. 2021 Jul 15:108723. doi: 10.1016/j.neuropharm.2021.108723. Online ahead of print.ABSTRACTAMPA receptors (AMPARs) are the major excitatory neurotransmitter receptor in the brain, and their expression at synapses is a critical determinant of synaptic transmission and therefore brain function. Synaptic plasticity involves increases or decreases in synaptic strength, caused by changes in the number or subunit-specific subtype of AMPARs expressed at synapses, and resulting in modifications of functional connectivity of neuronal circuits, a process which is thought to underpin learning and the formation or los...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Jonathan G Hanley Source Type: research

Interactions between the microbiota and enteric nervous system during gut-brain disorders
The objective of this review is to describe recent scientific elements that explore the communication between gut microbiota and the brain by focusing our interest on the enteric nervous system (ENS) as an intermediate partner. The ENS, which is known as the "second brain", could be under the direct or indirect influence of the gut microbiota and its released factors (short-chain fatty acids, neurotransmitters, gaseous factors, etc.). Thus, in addition to their actions on tissue (adipose tissue, liver, brain, etc.), microbes can have an impact on local ENS activity. This potential modification of ENS function has...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Steven Fried Eve Wemelle Patrice D Cani Claude Knauf Source Type: research

Cannabidiol effectively reverses mechanical and thermal allodynia, hyperalgesia, and anxious behaviors in a neuropathic pain model: Possible role of CB1 and TRPV1 receptors
This study presents a dose-response curve to understand better the effects of low doses (3 mg/kg) on CBD's antiallodynic and anxiolytic effects. Also, low doses of CBD were able to (1) reverse mechanical and thermal allodynia (cold) and hyperalgesia, (2) reverse anxious behaviors (reduction of the % of grooming and freezing time, and increase of the % of center time in the OFT) induced by chronic pain. The peripheral neuropathy promoted the increase in the expression of CB1 and TRPV1 receptors in the anterior cingulate cortex (ACC), anterior insular cortex (AIC), basolateral amygdala (BLA), dorsal hippocampus (DH), and ven...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Gleice K Silva-Cardoso Willian Lazarini-Lopes Jaime E Hallak Jos é A Crippa Antonio W Zuardi Norberto Garcia-Cairasco Christie R A Leite-Panissi Source Type: research

GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases
Neuropharmacology. 2021 Jul 15:108708. doi: 10.1016/j.neuropharm.2021.108708. Online ahead of print.ABSTRACTSynaptic transmission is one of the fundamental processes that all brain functions are based on. Changes in the strength of synaptic transmission among neurons are crucial for information processing in the central nervous system. The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of ionotropic glutamate receptors (AMPARs) mediate the majority of the fast excitatory synaptic transmission in the mammalian brain. Rapid trafficking of AMPARs in and out of the postsynaptic membrane is proposed to be a ...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Yuan Ge Yu Tian Wang Source Type: research

Metabotropic actions of kainate receptors modulating glutamate release
Neuropharmacology. 2021 Jul 15:108696. doi: 10.1016/j.neuropharm.2021.108696. Online ahead of print.ABSTRACTPresynaptic kainate (KA) receptors (KARs) modulate GABA and glutamate release in the central nervous system of mammals. While some of the actions of KARs are ionotropic, metabotropic actions for these receptors have also been seen to modulate both GABA and glutamate release. In general, presynaptic KARs modulate glutamate release through their metabotropic actions in a biphasic manner, with low KA concentrations producing an increase in glutamate release and higher concentrations of KA driving weaker release of this ...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Rafael Falc ón-Moya Antonio Rodr íguez-Moreno Source Type: research

Reduced neuroinflammation and enhanced neurogenesis following chronic agomelatine treatment in rats undergoing chronic constant light
Neuropharmacology. 2021 Jul 15:108706. doi: 10.1016/j.neuropharm.2021.108706. Online ahead of print.ABSTRACTExperimental studies have revealed the involvement of neuroinflammation mediated by activated microglia in the pathophysiology of depression, suggesting a novel target for treatment. The atypical antidepressant Agomelatine (Ago) has an advantage compared to the classical antidepressants due to its chronobiotic activity and unique pharmacological profile as a selective agonist at the melatonin receptors and an antagonist at the 5HT2C receptors. We have recently revealed that Ago can exert a potent antidepressant effec...
Source: Neuropharmacology - July 18, 2021 Category: Drugs & Pharmacology Authors: Dimitrinka Atanasova Nikolai Lazarov Dimo S Stoyanov Radoslav H Spassov Anton B Tonchev Jana Tchekalarova Source Type: research

Blocking NK1 receptors disrupts the sequential and temporal organization of chain grooming in rats
Neuropharmacology. 2021 Jul 14:108716. doi: 10.1016/j.neuropharm.2021.108716. Online ahead of print.ABSTRACTThe basal ganglia are a group of sub-cortical structures believed to play a critical role in action selection and sequencing. The striatum is the largest input structure of the basal ganglia and contains the neuropeptide substance P in abundance. Recent computational work has suggested that substance P could play a critical role in action sequence performance and acquisition, but this has not been tested experimentally before. The aim of the present study was to test how blocking substance P's main NK1-type receptors...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Natalia Favila Kevin Gurney Paul G Overton Source Type: research

Attenuated NMDAR signaling on fast-spiking interneurons in prefrontal cortex contributes to age-related decline of cognitive flexibility
In this study, one cohort of young adult (4 months) and aged (20 months) male F344 rats were characterized for cognitive flexibility on an operant set-shifting task. Expression of the essential NMDAR subunit, NR1, was correlated with individual differences in set-shifting abilities such that lower NR1 in the aged PFC was associated with worse set-shifting. In contrast, lower expression of two AMPAR subunits, GluR1 and GluR2, was not associated with set-shift abilities in aging. As NMDARs are expressed by both pyramidal cells and fast-spiking interneurons (FSI) in PFC, whole-cell patch clamp recordings were performed in a s...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Joseph A McQuail B Sofia Beas Kyle B Kelly Caesar M Hernandez Jennifer L Bizon Charles J Frazier Source Type: research

The gating pore blocker 1-(2,4-xylyl)guanidinium selectively inhibits pacemaking of midbrain dopaminergic neurons
Neuropharmacology. 2021 Jul 14:108722. doi: 10.1016/j.neuropharm.2021.108722. Online ahead of print.ABSTRACTAlthough several ionic mechanisms are known to control rate and regularity of the slow pacemaker in dopamine (DA) neurons, the core mechanism of pacing is controversial. Here we tested the hypothesis that pacemaking of SNc DA neurons is enabled by an unconventional conductance. We found that 1-(2,4-xylyl)guanidinium (XG), an established blocker of gating pore currents, selectively inhibits pacemaking of DA neurons. The compound inhibited all slow pacemaking DA neurons that were tested, both in the substantia nigra pa...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Kevin Jehasse Laurent Massotte Sebastian Hartmann Romain Vitello Sofian Ringlet Marie Vitello Han Chow Chua Stephan A Pless Dominique Engel Jean-Fran çois Liégeois Bernard Lakaye Jochen Roeper Vincent Seutin Source Type: research

Hippocampal neurogenesis interferes with extinction and reinstatement of methamphetamine-associated reward memory in mice
Neuropharmacology. 2021 Jul 14:108717. doi: 10.1016/j.neuropharm.2021.108717. Online ahead of print.ABSTRACTDrugs of abuse, including morphine and cocaine, can reduce hippocampal neurogenesis (HN). Whereas promotion of HN is being increasingly recognized as a promising strategy for treating morphine and cocaine addiction. The present study is focused on exploring the changes of HN during methamphetamine (METH) administration and further clarify if HN is involved in METH-associated reward memory. After successfully establishing the conditioned place preference (CPP) paradigm to simulate the METH-associated reward memory in ...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Xiaohang Che Yijun Bai Jialing Cai Yueyang Liu Yuting Li Meixue Yin Tianyu Xu Chunfu Wu Jingyu Yang Source Type: research

Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration
Neuropharmacology. 2021 Jul 14:108719. doi: 10.1016/j.neuropharm.2021.108719. Online ahead of print.ABSTRACTGlutamate is the primary excitatory neurotransmitter of the brain. Cellular homeostasis of glutamate is of paramount importance for normal brain function and relies on an intricate metabolic collaboration between neurons and astrocytes. Glutamate is extensively recycled between neurons and astrocytes in a process known as the glutamate-glutamine cycle. The recycling of glutamate is closely linked to brain energy metabolism and is essential to sustain glutamatergic neurotransmission. However, a considerable amount of ...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Jens V Andersen Kia H Markussen Emil Jakobsen Arne Schousboe Helle S Waagepetersen Paul A Rosenberg Blanca I Aldana Source Type: research

Biophysical and synaptic properties of NMDA receptors in the lateral habenula
Neuropharmacology. 2021 Jul 14;196:108718. doi: 10.1016/j.neuropharm.2021.108718. Online ahead of print.ABSTRACTExcitatory synaptic transmission in the lateral habenula (LHb), an evolutionarily ancient subcortical structure, encodes aversive stimuli and affective states. Habenular glutamatergic synapses contribute to these processes partly through the activation of AMPA receptors. Yet, N-methyl-d-aspartate receptors (NMDARs) are also expressed in the LHb and support the emergence of depressive symptoms. Indeed, local NMDAR blockade in the LHb rescues anhedonia and behavioral despair in rodent models of depression. However,...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Alvaro Nuno-Perez Sarah Mondoloni Anna Tchenio Salvatore Lecca Manuel Mameli Source Type: research

Blocking NK1 receptors disrupts the sequential and temporal organization of chain grooming in rats
Neuropharmacology. 2021 Jul 14:108716. doi: 10.1016/j.neuropharm.2021.108716. Online ahead of print.ABSTRACTThe basal ganglia are a group of sub-cortical structures believed to play a critical role in action selection and sequencing. The striatum is the largest input structure of the basal ganglia and contains the neuropeptide substance P in abundance. Recent computational work has suggested that substance P could play a critical role in action sequence performance and acquisition, but this has not been tested experimentally before. The aim of the present study was to test how blocking substance P's main NK1-type receptors...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Natalia Favila Kevin Gurney Paul G Overton Source Type: research

Attenuated NMDAR signaling on fast-spiking interneurons in prefrontal cortex contributes to age-related decline of cognitive flexibility
In this study, one cohort of young adult (4 months) and aged (20 months) male F344 rats were characterized for cognitive flexibility on an operant set-shifting task. Expression of the essential NMDAR subunit, NR1, was correlated with individual differences in set-shifting abilities such that lower NR1 in the aged PFC was associated with worse set-shifting. In contrast, lower expression of two AMPAR subunits, GluR1 and GluR2, was not associated with set-shift abilities in aging. As NMDARs are expressed by both pyramidal cells and fast-spiking interneurons (FSI) in PFC, whole-cell patch clamp recordings were performed in a s...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Joseph A McQuail B Sofia Beas Kyle B Kelly Caesar M Hernandez Jennifer L Bizon Charles J Frazier Source Type: research

The gating pore blocker 1-(2,4-xylyl)guanidinium selectively inhibits pacemaking of midbrain dopaminergic neurons
Neuropharmacology. 2021 Jul 14:108722. doi: 10.1016/j.neuropharm.2021.108722. Online ahead of print.ABSTRACTAlthough several ionic mechanisms are known to control rate and regularity of the slow pacemaker in dopamine (DA) neurons, the core mechanism of pacing is controversial. Here we tested the hypothesis that pacemaking of SNc DA neurons is enabled by an unconventional conductance. We found that 1-(2,4-xylyl)guanidinium (XG), an established blocker of gating pore currents, selectively inhibits pacemaking of DA neurons. The compound inhibited all slow pacemaking DA neurons that were tested, both in the substantia nigra pa...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Kevin Jehasse Laurent Massotte Sebastian Hartmann Romain Vitello Sofian Ringlet Marie Vitello Han Chow Chua Stephan A Pless Dominique Engel Jean-Fran çois Liégeois Bernard Lakaye Jochen Roeper Vincent Seutin Source Type: research

Hippocampal neurogenesis interferes with extinction and reinstatement of methamphetamine-associated reward memory in mice
Neuropharmacology. 2021 Jul 14:108717. doi: 10.1016/j.neuropharm.2021.108717. Online ahead of print.ABSTRACTDrugs of abuse, including morphine and cocaine, can reduce hippocampal neurogenesis (HN). Whereas promotion of HN is being increasingly recognized as a promising strategy for treating morphine and cocaine addiction. The present study is focused on exploring the changes of HN during methamphetamine (METH) administration and further clarify if HN is involved in METH-associated reward memory. After successfully establishing the conditioned place preference (CPP) paradigm to simulate the METH-associated reward memory in ...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Xiaohang Che Yijun Bai Jialing Cai Yueyang Liu Yuting Li Meixue Yin Tianyu Xu Chunfu Wu Jingyu Yang Source Type: research

Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration
Neuropharmacology. 2021 Jul 14:108719. doi: 10.1016/j.neuropharm.2021.108719. Online ahead of print.ABSTRACTGlutamate is the primary excitatory neurotransmitter of the brain. Cellular homeostasis of glutamate is of paramount importance for normal brain function and relies on an intricate metabolic collaboration between neurons and astrocytes. Glutamate is extensively recycled between neurons and astrocytes in a process known as the glutamate-glutamine cycle. The recycling of glutamate is closely linked to brain energy metabolism and is essential to sustain glutamatergic neurotransmission. However, a considerable amount of ...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Jens V Andersen Kia H Markussen Emil Jakobsen Arne Schousboe Helle S Waagepetersen Paul A Rosenberg Blanca I Aldana Source Type: research

Biophysical and synaptic properties of NMDA receptors in the lateral habenula
Neuropharmacology. 2021 Jul 14:108718. doi: 10.1016/j.neuropharm.2021.108718. Online ahead of print.ABSTRACTExcitatory synaptic transmission in the lateral habenula (LHb), an evolutionarily ancient subcortical structure, encodes aversive stimuli and affective states. Habenular glutamatergic synapses contribute to these processes partly through the activation of AMPA receptors. Yet, N-methyl-d-aspartate receptors (NMDARs) are also expressed in the LHb and support the emergence of depressive symptoms. Indeed, local NMDAR blockade in the LHb rescues anhedonia and behavioral despair in rodent models of depression. However, the...
Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Alvaro Nuno-Perez Sarah Mondoloni Anna Tchenio Salvatore Lecca Manuel Mameli Source Type: research

AMPA receptor trafficking and LTP: Carboxy-termini, amino-termini and TARPs
Neuropharmacology. 2021 Jul 13:108710. doi: 10.1016/j.neuropharm.2021.108710. Online ahead of print.ABSTRACTAMPA receptors (AMPARs) are fundamental elements in excitatory synaptic transmission and synaptic plasticity in the CNS. Long term potentiation (LTP), a form of synaptic plasticity which contributes to learning and memory formation, relies on the accumulation of AMPARs at the postsynapse. This phenomenon requires the coordinated recruitment of different elements in the AMPAR complex. Based on recent research reviewed herein, we propose an updated AMPAR trafficking and LTP model which incorporates both extracellular a...
Source: Neuropharmacology - July 16, 2021 Category: Drugs & Pharmacology Authors: Javier D íaz-Alonso Roger A Nicoll Source Type: research

Ionic and signaling mechanisms involved in neurotensin-mediated excitation of central amygdala neurons
Neuropharmacology. 2021 Jul 13:108714. doi: 10.1016/j.neuropharm.2021.108714. Online ahead of print.ABSTRACTNeurotensin (NT) serves as a neuromodulator in the brain where it regulates a variety of physiological functions. Whereas the central amygdala (CeA) expresses NT peptide and NTS1 receptors and application of NT has been shown to excite CeA neurons, the underlying cellular and molecular mechanisms have not been determined. We found that activation of NTS1 receptors increased the neuronal excitability of the lateral nucleus (CeL) of CeA. Both phospholipase Cβ (PLCβ) and phosphatidylinositol 4,5-bisphosphate (...
Source: Neuropharmacology - July 16, 2021 Category: Drugs & Pharmacology Authors: Saobo Lei Binqi Hu Source Type: research

Nicotine: understanding the big picture while also studying the details
Neuropharmacology. 2021 Jul 13:108715. doi: 10.1016/j.neuropharm.2021.108715. Online ahead of print.NO ABSTRACTPMID:34271018 | DOI:10.1016/j.neuropharm.2021.108715 (Source: Neuropharmacology)
Source: Neuropharmacology - July 16, 2021 Category: Drugs & Pharmacology Authors: Roger L Papke Mariella De Biasi M Imad Damaj Source Type: research

Effects of alcohol on brain oxygenation and brain hypoxia induced by intravenous heroin
Neuropharmacology. 2021 Jul 13:108713. doi: 10.1016/j.neuropharm.2021.108713. Online ahead of print.ABSTRACTAlcohol is the most commonly used psychoactive drug, often taken in conjunction with opioid drugs. Since both alcohol and opioids can induce CNS depression, it is often assumed that alcohol potentiates the known hypoxic effects of opioid drugs, thus contributing to coma and death during opioid overdose. To address this supposition, we used oxygen sensors to examine the effects of alcohol on brain oxygenation and hypoxic responses induced by intravenous heroin in awake, freely moving rats. To eliminate robust sensory ...
Source: Neuropharmacology - July 16, 2021 Category: Drugs & Pharmacology Authors: Shruthi A Thomas Carlos M Curay Eugene A Kiyatkin Source Type: research

Biology of AMPA receptor interacting proteins - From biogenesis to synaptic plasticity
Neuropharmacology. 2021 Jul 13:108709. doi: 10.1016/j.neuropharm.2021.108709. Online ahead of print.ABSTRACTAMPA-type glutamate receptors mediate the majority of excitatory synaptic transmission in the central nervous system. Their signaling properties and abundance at synapses are both crucial determinants of synapse efficacy and plasticity, and are therefore under sophisticated control. Unique to this ionotropic glutamate receptor (iGluR) is the abundance of interacting proteins that contribute to its complex regulation. These include transient interactions with the receptor cytoplasmic tail as well as the N-terminal dom...
Source: Neuropharmacology - July 16, 2021 Category: Drugs & Pharmacology Authors: Peter M Matthews Alexandra Pinggera Domen Kampjut Ingo H Greger Source Type: research

AMPA receptors in the synapse: Very little space and even less time
Neuropharmacology. 2021 Jul 13:108711. doi: 10.1016/j.neuropharm.2021.108711. Online ahead of print.ABSTRACTGlutamate is by far the most abundant neurotransmitter used by excitatory synapses in the vertebrate central nervous system. Once released into the synaptic cleft, it depolarises the postsynaptic membrane and activates downstream signalling pathways resulting in the propagation of the excitatory signal. Initial depolarisation is primarily mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. These ion channels are the first ones to get activated by released glutamate and their kinetics,...
Source: Neuropharmacology - July 16, 2021 Category: Drugs & Pharmacology Authors: Jelena Baranovic Source Type: research

Activation of the spinal EGFR signaling pathway in a rat model of cancer-induced bone pain with morphine tolerance
In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibias of rats to provoke cancer-induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We observed sustained increased in the protein levels of EGFR, p-EGFR, ERK1/2, and p-ERK1/2 during the development of morphine tolerance in rats with cancer-induced bone pain by western blotting. The EGFR level was significantly increased in the MT and CIBP + MT groups, and EGFR was colocalized with markers of microglia and neurons in the spinal cords of rats. Inhibition of EGFR by a...
Source: Neuropharmacology - July 14, 2021 Category: Drugs & Pharmacology Authors: Yaqiong Yang Zhifeng Chen Rong Hu Yu Sun None Xiang Lv Jia Yan Hong Jiang Source Type: research

Activation of the spinal EGFR signaling pathway in a rat model of cancer-induced bone pain with morphine tolerance
In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibias of rats to provoke cancer-induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We observed sustained increased in the protein levels of EGFR, p-EGFR, ERK1/2, and p-ERK1/2 during the development of morphine tolerance in rats with cancer-induced bone pain by western blotting. The EGFR level was significantly increased in the MT and CIBP + MT groups, and EGFR was colocalized with markers of microglia and neurons in the spinal cords of rats. Inhibition of EGFR by a...
Source: Neuropharmacology - July 14, 2021 Category: Drugs & Pharmacology Authors: Yaqiong Yang Zhifeng Chen Rong Hu Yu Sun None Xiang Lv Jia Yan Hong Jiang Source Type: research

Activation of the spinal EGFR signaling pathway in a rat model of cancer-induced bone pain with morphine tolerance
In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibias of rats to provoke cancer-induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We observed sustained increased in the protein levels of EGFR, p-EGFR, ERK1/2, and p-ERK1/2 during the development of morphine tolerance in rats with cancer-induced bone pain by western blotting. The EGFR level was significantly increased in the MT and CIBP + MT groups, and EGFR was colocalized with markers of microglia and neurons in the spinal cords of rats. Inhibition of EGFR by a...
Source: Neuropharmacology - July 14, 2021 Category: Drugs & Pharmacology Authors: Yaqiong Yang Zhifeng Chen Rong Hu Yu Sun None Xiang Lv Jia Yan Hong Jiang Source Type: research