Transcriptome changes in the nucleus of the solitary tract induced by repeated stress, alcohol dependence, or stress-induced drinking in dependent mice
Neuropharmacology. 2023 Oct 19:109768. doi: 10.1016/j.neuropharm.2023.109768. Online ahead of print.ABSTRACTStress increases alcohol consumption in dependent animals and contributes to the development of alcohol use disorder. The nucleus of the solitary tract (NTS) is a critical brainstem region for integrating and relaying central and peripheral signals to regulate stress responses, but it is not known if it plays a role in alcohol dependence- or in stress-induced escalations in alcohol drinking in dependent mice. Here, we used RNA-sequencing and bioinformatics analyses to study molecular adaptations in the NTS of C57BL/6...
Source: Neuropharmacology - October 21, 2023 Category: Drugs & Pharmacology Authors: Emily K Grantham Gayatri R Tiwari Olga Ponomereva R Adron Harris Marcello F Lopez Howard C Becker R Dayne Mayfield Source Type: research

Temporal dynamics of BDNF signaling recruitment in the rat prefrontal cortex and hippocampus following a single infusion of a translational dose of ketamine
In this report, we investigated the effects of a ketamine dosing mode in male Sprague-Dawley rats showed to be translational to the clinically effective mode in patients. We focused on the first 24 h after infusion to finely dissect potential differences in the contribution of BDNF signaling pathway in prefrontal cortex and hippocampus, two brain regions involved in the antidepressant effects of ketamine. Our data show that the slow ketamine infusion activates the BDNF-mTOR-S6 pathway in prefrontal cortex as early as 2 h and remains on until at least 6 h after the infusion. At the 12 h timepoint, this pathway is turned off...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Lucia Caffino Francesca Mottarlini Alessandro Piva Beatrice Rizzi Fabio Fumagalli Cristiano Chiamulera Source Type: research

Ventral hippocampus is more sensitive to fluoxetine-induced changes in extracellular 5-HT concentration, membrane 5-HT transporter level and immobility times
Neuropharmacology. 2023 Oct 17:109766. doi: 10.1016/j.neuropharm.2023.109766. Online ahead of print.ABSTRACTHippocampal responses to selective 5-HT reuptake inhibitor (SSRI) have long been studied. However, its sub-regional involvements in mediating SSRI's pharmacological effects have not been fully addressed. The current study sought to investigate neurochemical, neurobiological and neurobehavioral changes in response to direct fluoxetine perfusion into the ventral and dorsal sub-regions of the hippocampus in C57BL/6 mice. Following fluoxetine perfusion, time courses of dialysate 5-HT, 5-HT transporter (5-HTT) protein (to...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Xiang Li Dan Feng Shenglu Ma Mingxing Li Shulei Zhao Man Tang Source Type: research

Neuropeptide S Receptor variant (I107N) regulates behavioral characteristics and NPS effect in mice in a sex-dependent manner
Neuropharmacology. 2023 Oct 17:109771. doi: 10.1016/j.neuropharm.2023.109771. Online ahead of print.ABSTRACTAccumulated data demonstrate that the A/T single-nucleotide polymorphism (SNP) rs324981 in the human neuropeptide S receptor 1 (NPSR1) gene, resulting in an amino acid change from asparagine (N) to isoleucine (I) at position 107, is associated with susceptibility to psychiatric disorders. Neuropeptide S (NPS) has also been implicated in modulating these disorders in rodent experiments. However, the effect of this SNP on NPSR1 activity remains unclear. To elucidate the pathophysiological and pharmacological implicatio...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Chen Song Zhi-Chen Zhu Chuan-Chuan Liu Wen-Xin Yun Zhi-Yuan Wang Guan-Yi Lu Rui Song Ning Wu Jin Li Fei Li Source Type: research

Catechol-O-Methyltransferase inhibition and alcohol use disorder: Evaluating the efficacy of tolcapone in ethanol-dependent rats
In this study, we evaluated the effects of tolcapone on operant, oral ethanol self-administration in non-dependent and dependent rats, and in rats that self-administered oral saccharin. To induce dependence, rats underwent the chronic intermittent exposure to vapor model, and their drinking levels were assessed during acute withdrawal from ethanol. Our results demonstrated that tolcapone attenuated responding for ethanol in dependent rats only, without affecting self-administration in nondependent rats or rats self-administering saccharin. Moreover, we found that tolcapone was differentially effective in different estrous ...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Michelle R Doyle Selen Dirik Angelica R Martinez Talyn E Hughes Mohini R Iyer Elizabeth A Sneddon Hyeonglim Seo Seth M Cohen Giordano de Guglielmo Source Type: research

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats
Neuropharmacology. 2023 Oct 18:109765. doi: 10.1016/j.neuropharm.2023.109765. Online ahead of print.ABSTRACTSignificant exposure to alcohol or cannabis during adolescence can induce lasting disruptions of neuronal signaling in brain regions that are later to mature, such as the medial prefrontal cortex (mPFC). Considerably less is known about the effects of alcohol and cannabis co-use, despite its common occurrence. Here, we used male and female Long-Evans rats to investigate the effects of early-life exposure to ethanol, delta-9-tetrahydrocannabinol (THC), or their combination on high frequency stimulation (HFS)-induced p...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Linyuan Shi Shuo Kang Chan Young Choi Brynn L Noonan Lauren K Carrica Nu-Chu Liang Joshua M Gulley Source Type: research

Temporal dynamics of BDNF signaling recruitment in the rat prefrontal cortex and hippocampus following a single infusion of a translational dose of ketamine
In this report, we investigated the effects of a ketamine dosing mode in male Sprague-Dawley rats showed to be translational to the clinically effective mode in patients. We focused on the first 24 h after infusion to finely dissect potential differences in the contribution of BDNF signaling pathway in prefrontal cortex and hippocampus, two brain regions involved in the antidepressant effects of ketamine. Our data show that the slow ketamine infusion activates the BDNF-mTOR-S6 pathway in prefrontal cortex as early as 2 h and remains on until at least 6 h after the infusion. At the 12 h timepoint, this pathway is turned off...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Lucia Caffino Francesca Mottarlini Alessandro Piva Beatrice Rizzi Fabio Fumagalli Cristiano Chiamulera Source Type: research

Ventral hippocampus is more sensitive to fluoxetine-induced changes in extracellular 5-HT concentration, membrane 5-HT transporter level and immobility times
Neuropharmacology. 2023 Oct 17:109766. doi: 10.1016/j.neuropharm.2023.109766. Online ahead of print.ABSTRACTHippocampal responses to selective 5-HT reuptake inhibitor (SSRI) have long been studied. However, its sub-regional involvements in mediating SSRI's pharmacological effects have not been fully addressed. The current study sought to investigate neurochemical, neurobiological and neurobehavioral changes in response to direct fluoxetine perfusion into the ventral and dorsal sub-regions of the hippocampus in C57BL/6 mice. Following fluoxetine perfusion, time courses of dialysate 5-HT, 5-HT transporter (5-HTT) protein (to...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Xiang Li Dan Feng Shenglu Ma Mingxing Li Shulei Zhao Man Tang Source Type: research

Neuropeptide S Receptor variant (I107N) regulates behavioral characteristics and NPS effect in mice in a sex-dependent manner
Neuropharmacology. 2023 Oct 17:109771. doi: 10.1016/j.neuropharm.2023.109771. Online ahead of print.ABSTRACTAccumulated data demonstrate that the A/T single-nucleotide polymorphism (SNP) rs324981 in the human neuropeptide S receptor 1 (NPSR1) gene, resulting in an amino acid change from asparagine (N) to isoleucine (I) at position 107, is associated with susceptibility to psychiatric disorders. Neuropeptide S (NPS) has also been implicated in modulating these disorders in rodent experiments. However, the effect of this SNP on NPSR1 activity remains unclear. To elucidate the pathophysiological and pharmacological implicatio...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Chen Song Zhi-Chen Zhu Chuan-Chuan Liu Wen-Xin Yun Zhi-Yuan Wang Guan-Yi Lu Rui Song Ning Wu Jin Li Fei Li Source Type: research

Catechol-O-Methyltransferase inhibition and alcohol use disorder: Evaluating the efficacy of tolcapone in ethanol-dependent rats
In this study, we evaluated the effects of tolcapone on operant, oral ethanol self-administration in non-dependent and dependent rats, and in rats that self-administered oral saccharin. To induce dependence, rats underwent the chronic intermittent exposure to vapor model, and their drinking levels were assessed during acute withdrawal from ethanol. Our results demonstrated that tolcapone attenuated responding for ethanol in dependent rats only, without affecting self-administration in nondependent rats or rats self-administering saccharin. Moreover, we found that tolcapone was differentially effective in different estrous ...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Michelle R Doyle Selen Dirik Angelica R Martinez Talyn E Hughes Mohini R Iyer Elizabeth A Sneddon Hyeonglim Seo Seth M Cohen Giordano de Guglielmo Source Type: research

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats
Neuropharmacology. 2023 Oct 18:109765. doi: 10.1016/j.neuropharm.2023.109765. Online ahead of print.ABSTRACTSignificant exposure to alcohol or cannabis during adolescence can induce lasting disruptions of neuronal signaling in brain regions that are later to mature, such as the medial prefrontal cortex (mPFC). Considerably less is known about the effects of alcohol and cannabis co-use, despite its common occurrence. Here, we used male and female Long-Evans rats to investigate the effects of early-life exposure to ethanol, delta-9-tetrahydrocannabinol (THC), or their combination on high frequency stimulation (HFS)-induced p...
Source: Neuropharmacology - October 20, 2023 Category: Drugs & Pharmacology Authors: Linyuan Shi Shuo Kang Chan Young Choi Brynn L Noonan Lauren K Carrica Nu-Chu Liang Joshua M Gulley Source Type: research

Optogenetic inhibition of spinal inhibitory neurons facilitates mechanical responses of spinal wide dynamic range neurons and causes mechanical hypersensitivity
In this study, we established a novel experimental method to analyze temporal activity of DH neurons during the optogenetically induced disinhibition state by combining extracellular recording and optogenetics. We investigated how specific and temporally restricted dysfunction of DH inhibitory neurons affected spinal neuronal activities evoked by cutaneous mechanical stimulation. In behavioral experiments, the specific and temporally restricted spinal optogenetic suppression of DH inhibitory neurons induced mechanical hypersensitivity. Furthermore, this manipulation enhanced the mechanical responses of wide dynamic range (...
Source: Neuropharmacology - October 18, 2023 Category: Drugs & Pharmacology Authors: Yuka Fujiwara Keisuke Koga Nozomu H Nakamura Keishi Maruo Toshiya Tachibana Hidemasa Furue Source Type: research

Optogenetic inhibition of spinal inhibitory neurons facilitates mechanical responses of spinal wide dynamic range neurons and causes mechanical hypersensitivity
In this study, we established a novel experimental method to analyze temporal activity of DH neurons during the optogenetically induced disinhibition state by combining extracellular recording and optogenetics. We investigated how specific and temporally restricted dysfunction of DH inhibitory neurons affected spinal neuronal activities evoked by cutaneous mechanical stimulation. In behavioral experiments, the specific and temporally restricted spinal optogenetic suppression of DH inhibitory neurons induced mechanical hypersensitivity. Furthermore, this manipulation enhanced the mechanical responses of wide dynamic range (...
Source: Neuropharmacology - October 18, 2023 Category: Drugs & Pharmacology Authors: Yuka Fujiwara Keisuke Koga Nozomu H Nakamura Keishi Maruo Toshiya Tachibana Hidemasa Furue Source Type: research

CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum
Neuropharmacology. 2023 Oct 14:109759. doi: 10.1016/j.neuropharm.2023.109759. Online ahead of print.ABSTRACTCHIR99021, also known as laduviglusib or CT99021, is a Glycogen-synthase kinase 3β (GSK3β) inhibitor, which has been reported as a promising drug for cardiomyocyte regeneration or treatment of sensorial hearing loss. Since the activation of dopamine (DA) receptors regulates dopamine synthesis and they can signal through the β-arrestin pathway and GSK3β, we decided to check the effect of GSK3β inhibitors (CHIR99021, SB216763 and lithium ion) on the control of DA synthesis. Using ex vivo experiments with minces fr...
Source: Neuropharmacology - October 16, 2023 Category: Drugs & Pharmacology Authors: Sally Hamdon Pol Fernandez-Gonzalez Muhammad Yusof Omar Marta Gonz ález-Sepúlveda Jordi Ortiz Carles Gil Source Type: research

Fluoroethylnormemantine (FENM) shows synergistic protection in combination with a sigma-1 receptor agonist in a mouse model of Alzheimer's disease
Neuropharmacology. 2023 Oct 14:109733. doi: 10.1016/j.neuropharm.2023.109733. Online ahead of print.ABSTRACTFluoroethylnormemantine (FENM) is a Memantine derivative with anti-amnesic and neuroprotective activities showed in the Aβ25-35 pharmacological mouse model of Alzheimer's disease (AD). As AD is a complex multi-factorial neurodegenerative pathology, combination therapies relying on drugs acting through different pathways, have been suggested to more adequately address neuroprotection. As several agonists of the sigma-1 receptor (S1R), an intracellular chaperone, are presently in phase 2 or 3 clinical trials in neurod...
Source: Neuropharmacology - October 16, 2023 Category: Drugs & Pharmacology Authors: Aline Freyssin Allison Carles Sarra Guehairia Gilles Rubinstenn Tangui Maurice Source Type: research