Small conductance calcium activated potassium (SK) channel dependent and independent effects of riluzole on neuropathic pain-related amygdala activity and behaviors in rats.
CONCLUSIONS AND IMPLICATIONS: The results suggest that riluzole has beneficial effects on neuropathic pain behaviors through SK channel dependent and independent mechanisms in the amygdala. PMID: 29908238 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 13, 2018 Category: Drugs & Pharmacology Authors: Thompson JM, Yakhnitsa V, Ji G, Neugebauer V Tags: Neuropharmacology Source Type: research

The psychostimulant ( ±)-cis-4,4'-dimethylaminorex (4,4'-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters.
The psychostimulant (±)-cis-4,4'-dimethylaminorex (4,4'-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters. Neuropharmacology. 2018 Jun 13;: Authors: Maier J, Mayer FP, Luethi D, Holy M, Jäntsch K, Reither H, Hirtler L, Hoener MC, Liechti ME, Pifl C, Brandt SD, Sitte HH Abstract (±)-cis-4,4'-Dimethylaminorex (4,4'-DMAR) is a new psychoactive substance (NPS) that has been associated with 31 fatalities and other adverse events in Europe between June 2013 and February 2014. We used in vitro uptake inhibition and transporter release assays to determine the effe...
Source: Neuropharmacology - June 13, 2018 Category: Drugs & Pharmacology Authors: Maier J, Mayer FP, Luethi D, Holy M, Jäntsch K, Reither H, Hirtler L, Hoener MC, Liechti ME, Pifl C, Brandt SD, Sitte HH Tags: Neuropharmacology Source Type: research

The GABAergic Gudden's dorsal tegmental nucleus: A new relay for serotonergic regulation of sleep-wake behavior in the mouse.
Abstract Serotonin (5-HT) neurons are involved in wake promotion and exert a strong inhibitory influence on rapid eye movement (REM) sleep. Such effects have been ascribed, at least in part to the action of 5-HT at post-synaptic 5-HT1A receptors (5-HT1AR) in the brainstem, a major wake/REM sleep regulatory center. However, the neuroanatomical substrate through which 5-HT1AR influence sleep remains elusive. We therefore investigated whether a brainstem structure containing a high density of 5-HT1AR mRNA, the GABAergic Gudden's dorsal tegmental nucleus (DTg), may contribute to 5-HT-mediated regulatory mechanisms of ...
Source: Neuropharmacology - June 13, 2018 Category: Drugs & Pharmacology Authors: Chazalon M, Dumas S, Bernard JF, Sahly I, Tronche F, de Kerchove d'Exaerde A, Hamon M, Adrien J, Fabre V, Bonnavion P Tags: Neuropharmacology Source Type: research

Environmental enrichment enhances conditioned place preference to ethanol via an oxytocinergic-dependent mechanism in male mice.
This study offers a unique prospective on the neurobiological understanding of the initial stages of alcohol use/misuse driven by complex environmental-social interplay. PMID: 29908241 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 13, 2018 Category: Drugs & Pharmacology Authors: Rae M, Zanos P, Georgiou P, Chivers P, Bailey A, Camarini R Tags: Neuropharmacology Source Type: research

Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats.
Abstract Medium-chain triglycerides (MCT) are emerging as unique dietary supplements potentially relevant to improve brain dysfunctions. MCT are converted into ketones and free medium chain fatty acids that, in the brain, are highly effective energy sources to mitochondria and potentially less harmful than glucose metabolism to neurons. Given the recently established link between mitochondrial dysfunction and high anxiety and depression, we set this study to investigate the effectiveness of an MCT-enriched diet to ameliorate anxiety- and depression-related behaviors in rats. Male rats were distributed into two gro...
Source: Neuropharmacology - June 13, 2018 Category: Drugs & Pharmacology Authors: Hollis F, Mitchell ES, Canto C, Wang D, Sandi C Tags: Neuropharmacology Source Type: research

A SNAP-25 cleaving chimera of botulinum neurotoxin /A and /E prevents TNF α-induced elevation of the activities of native TRP channels on early postnatal rat dorsal root ganglion neurons.
A SNAP-25 cleaving chimera of botulinum neurotoxin /A and /E prevents TNFα-induced elevation of the activities of native TRP channels on early postnatal rat dorsal root ganglion neurons. Neuropharmacology. 2018 Jun 12;: Authors: Nugent M, Yusef YR, Meng J, Wang J, Dolly JO Abstract Transient receptor potential (TRP) vallinoid 1 (TRPV1) and ankyrin 1 (TRPA1) are two transducing channels expressed on peripheral sensory nerves involved in pain sensation. Upregulation of their expression, stimulated by inflammatory cytokines and growth factors in animal pain models, correlate with the induction of n...
Source: Neuropharmacology - June 12, 2018 Category: Drugs & Pharmacology Authors: Nugent M, Yusef YR, Meng J, Wang J, Dolly JO Tags: Neuropharmacology Source Type: research

Overexpression of miRNA-137 in the brain suppresses seizure activity and neuronal excitability: A new potential therapeutic strategy for epilepsy.
Abstract miRNA-137 is an extremely abundant miRNA in the central nervous system and is thought to be closely related to synaptic plasticity. Here, we report a previously unrecognized role of miRNA-137 in epilepsy. The expression of miRNA-137 was decreased both in patients with temporal lobe epilepsy (TLE) and in two different mouse models of epilepsy. Overexpression of miRNA-137 induced by an intrahippocampal injection of a specific agomir prolonged the latency to spontaneous recurrent seizures (SRSs) and reduced seizure severity in a mouse model of pilocarpine-induced epilepsy. Elevated levels of miRNA-137 also p...
Source: Neuropharmacology - June 9, 2018 Category: Drugs & Pharmacology Authors: Wang W, Guo Y, He L, Chen C, Luo J, Ma Y, Li J, Yang Y, Yang Q, Du C, Zhang Y, Li Z, Xu X, Tian X, Wang X Tags: Neuropharmacology Source Type: research

CNS distribution, signalling properties and central effects of G-protein coupled receptor 4.
Abstract Information on the distribution and biology of the G-protein coupled receptor 4 (GPR4) in the brain is limited. It is currently thought that GPR4 couples to Gs proteins and may mediate central respiratory sensitivity to CO2. Using a knock-in mouse model, abundant GPR4 expression was detected in the cerebrovascular endothelium and neurones of dorsal raphe, retro-trapezoidal nucleus locus coeruleus and lateral septum. A similar distribution was confirmed using RNAscope in situ hybridisation. In HEK293 cells, overexpressing GPR4, it was highly constitutively active at neutral pH with little further increas...
Source: Neuropharmacology - June 9, 2018 Category: Drugs & Pharmacology Authors: Hosford PS, Mosienko V, Kishi K, Jurisic G, Seuwen K, Kinzel B, Ludwig MG, Wells JA, Christie IN, Koolen L, Abdala AP, Liu BH, Gourine AV, Teschemacher AG, Kasparov S Tags: Neuropharmacology Source Type: research

Muscarinic acetylcholine receptors in the central nervous system.
PMID: 29894772 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 9, 2018 Category: Drugs & Pharmacology Authors: Bradley SJ, Tobin AB, Prihandoko R Tags: Neuropharmacology Source Type: research

Dysregulation and restoration of homeostatic network plasticity in fragile X syndrome mice.
Abstract Chronic activity perturbations in neurons induce homeostatic plasticity through modulation of synaptic strength or other intrinsic properties to maintain the correct physiological range of excitability. Although similar plasticity can also occur at the population level, what molecular mechanisms are involved remain unclear. In the current study, we utilized a multielectrode array (MEA) recording system to evaluate homeostatic neural network activity of primary mouse cortical neuron cultures. We demonstrated that chronic elevation of neuronal activity through the inhibition of GABA(A) receptors elicits syn...
Source: Neuropharmacology - June 8, 2018 Category: Drugs & Pharmacology Authors: Jewett KA, Lee KY, Eagleman DE, Soriano S, Tsai NP Tags: Neuropharmacology Source Type: research

Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage.
In conclusion, rOPN attenuated ICH-induced brain inflammation in hyperglycemic rats, leading to attenuation of brain edema and improving neurological functions. Effects of rOPN were mediated at least partly by integrin-β1 induced inhibition of JAK2/STAT1 pathway. PMID: 29885817 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 7, 2018 Category: Drugs & Pharmacology Authors: Gong L, Manaenko A, Fan R, Huang L, Enkhjargal B, McBride D, Ding Y, Tang J, Xiao X, Zhang JH Tags: Neuropharmacology Source Type: research

Secondary Brain Injury: Predicting and Preventing Insults.
Abstract Mortality or severe disability affects the majority of patients after severe traumatic brain injury (TBI). Adherence to the brain trauma foundation guidelines has overall improved outcomes; however, traditional as well as novel interventions towards intracranial hypertension and secondary brain injury have come under scrutiny after series of negative randomized controlled trials. In fact, it would not be unfair to say there has been no single major breakthrough in the management of severe TBI in the last two decades. One plausible hypothesis for the aforementioned failures is that by the time treatment is...
Source: Neuropharmacology - June 6, 2018 Category: Drugs & Pharmacology Authors: Lazaridis C, Rusin CG, Robertson CS Tags: Neuropharmacology Source Type: research

Sub-efficacious doses of phosphodiesterase 4 and 5 inhibitors improve memory in a mouse model of Alzheimer's disease.
Abstract Cyclic nucleotides cAMP and cGMP cooperate to ensure memory acquisition and consolidation. Increasing their levels by phosphodiesterase inhibitors (PDE-Is) enhanced cognitive functions and rescued memory loss in different models of aging and Alzheimer's disease (AD). However, side effects due to the high doses used limited their application in humans. Based on previous studies suggesting that combinations of sub-efficacious doses of cAMP- and cGMP-specific PDE-Is improved synaptic plasticity and memory in physiological conditions, here we aimed to study whether this treatment was effective to counteract t...
Source: Neuropharmacology - June 6, 2018 Category: Drugs & Pharmacology Authors: Gulisano W, Tropea MR, Arancio O, Palmeri A, Puzzo D Tags: Neuropharmacology Source Type: research

Some distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity.
We report that ketamine inhibits STP in a double sigmoidal fashion with low (40 nM) and high (5.6 μM) IC50 values. In contrast, ketamine inhibits LTP in a single sigmoidal manner (IC50 value ∼ 15 μM). A GluN2D-subunit preferring NMDA receptor antagonist, UBP145, has a similar pharmacological profile. We propose that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory. PMID: 29885421 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 6, 2018 Category: Drugs & Pharmacology Authors: Ingram R, Kang H, Lightman S, Jane DE, Bortolotto ZA, Collingridge GL, Lodge D, Volianskis A Tags: Neuropharmacology Source Type: research

Plasminogen activator system homeostasis and its dysregulation by ethanol in astrocyte cultures and the developing brain.
In conclusion, astrocyte PA system may play a major role in the modulation of neuronal plasticity; ethanol-induced upregulation of tPA levels and plasmin activity may be responsible for altered neuronal plasticity in FASD. PMID: 29885422 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 6, 2018 Category: Drugs & Pharmacology Authors: Wilhelm CJ, Hashimoto JG, Roberts ML, Zhang X, Goeke CM, Bloom SH, Guizzetti M Tags: Neuropharmacology Source Type: research

Intranasal administration of progesterone: A potential efficient route of delivery for cerebroprotection after acute brain injuries.
ern C Abstract Progesterone has been shown to be cerebroprotective in different experimental models of brain injuries and neurodegenerative diseases. The preclinical data provided great hope for its use in humans. The failure of Phase 3 clinical trials to demonstrate the cerebroprotective efficiency of progesterone in traumatic brain injury (TBI) patients emphasizes that different aspects of the design of both experimental and clinical studies should be reviewed and refined. One important aspect to consider is to test different routes of delivery of therapeutic agents. Several studies have shown that the intranasa...
Source: Neuropharmacology - June 6, 2018 Category: Drugs & Pharmacology Authors: Guennoun R, Fréchou M, Gaignard P, Liere P, Slama A, Schumacher M, Denier C, Mattern C Tags: Neuropharmacology Source Type: research

Anti- β2GPI/β2GPI induces neutrophil extracellular traps formation to promote thrombogenesis via the TLR4/MyD88/MAPKs axis activation.
Anti-β2GPI/β2GPI induces neutrophil extracellular traps formation to promote thrombogenesis via the TLR4/MyD88/MAPKs axis activation. Neuropharmacology. 2018 Jun 05;: Authors: Zha C, Zhang W, Gao F, Xu J, Jia R, Cai J, Liu Y Abstract Antiphospholipid antibodies (aPLs) are a large group of heterogeneous antibodies that bind to anionic phospholipids alone or in combination with phospholipid binding proteins. Increasing evidence has converged to indicate that aPLs especially anti-β2 glycoprotein I antibody (anti-β2GPI) correlate with stroke severity and outcome. Though studies have sh...
Source: Neuropharmacology - June 5, 2018 Category: Drugs & Pharmacology Authors: Zha C, Zhang W, Gao F, Xu J, Jia R, Cai J, Liu Y Tags: Neuropharmacology Source Type: research

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal.
In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD. PMID: 29879408 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - June 4, 2018 Category: Drugs & Pharmacology Authors: Turner AC, Kraev I, Stewart MG, Stramek A, Overton PG, Dommett EJ Tags: Neuropharmacology Source Type: research

Importance of kynurenine 3-monooxygenase for spontaneous firing and pharmacological responses of midbrain dopamine neurons: relevance for schizophrenia.
Abstract Kynurenine 3-monooxygenase (KMO) is an essential enzyme of the kynurenine pathway, converting kynurenine into 3-hydroxykynurenine. Inhibition of KMO increases kynurenine, resulting in elevated levels of kynurenic acid (KYNA), an endogenous N-methyl-D-aspartate and α*7-nicotinic receptor antagonist. The concentration of KYNA is elevated in the brain of patients with schizophrenia, possibly as a result of a reduced KMO activity.In the present study, using in vivo single cell recording techniques, we investigated the electrophysiological characteristics of ventral tegmental area dopamine (VTA DA) neuro...
Source: Neuropharmacology - June 4, 2018 Category: Drugs & Pharmacology Authors: Tufvesson-Alm M, Schwieler L, Schwarcz R, Goiny M, Erhardt S, Engberg G Tags: Neuropharmacology Source Type: research

Amphetamine improves mouse and human attention in the 5-choice continuous performance test.
Abstract Non-medical use of prescription stimulants amongst college students is common, with claims of cognitive and academic benefits. The mechanism, magnitude, and pervasiveness of the cognitive enhancing effects of stimulants in healthy adults remain poorly understood however. The present study determined the effects of dextroamphetamine (D-amp) on the 5-choice continuous performance test (5C-CPT) of attention in healthy young adult humans and mice. A mixed gender sample received placebo (n = 29), 10 (n = 17) or 20 mg D-amp (n = 25) in a double-blind fashion before 5C-CPT testing. In addition, mal...
Source: Neuropharmacology - May 31, 2018 Category: Drugs & Pharmacology Authors: MacQueen DA, Minassian A, Kenton JA, Geyer MA, Perry W, Brigman JL, Young JW Tags: Neuropharmacology Source Type: research

GDNF revisited: A novel mammalian cell-derived variant form of GDNF increases dopamine turnover and improves brain biodistribution.
Abstract Parkinson's disease (PD) is a disorder affecting dopamine neurons for which there is no cure. Glial cell line-derived neurotrophic factor (GDNF) and the closely related protein neurturin are two trophic factors with demonstrated neuroprotective and neurorestorative properties on dopamine neurons in multiple animal species. However, GDNF and neurturin Phase-2 clinical trials have failed to demonstrate a significant level of improvement over placebo controls. Insufficient drug distribution in the brain parenchyma has been proposed as a major contributing factor for the lack of clinical efficacy in the Phase...
Source: Neuropharmacology - May 29, 2018 Category: Drugs & Pharmacology Authors: Grondin R, Littrell OM, Zhang Z, Ai Y, Huettl P, Pomerleau F, Quintero JE, Andersen AH, Stenslik MJ, Bradley LH, Lemmon J, O'Neill MJ, Gash DM, Gerhardt GA Tags: Neuropharmacology Source Type: research

Pharmacological inhibiton of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation.
Abstract The endocannabinoid system is a key modulator of memory consolidation for aversive experiences. We recently found that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases anandamide levels by inhibiting its hydrolysis, facilitates memory consolidation through a concurrent activation of both cannabinoid receptor type 1 (CB1) and 2 (CB2). Here, we investigated the role played on memory consolidation by the other major endocannabinoid, 2-arachidonoylglycerol (2-AG). To this aim, we tested the effects of pharmacological inhibition of monoacylglycerol lipase (MAGL) through systemic administ...
Source: Neuropharmacology - May 26, 2018 Category: Drugs & Pharmacology Authors: Ratano P, Petrella C, Forti F, Passeri PP, Morena M, Palmery M, Trezza V, Severini C, Campolongo P Tags: Neuropharmacology Source Type: research

Cooperative and dissociable involvement of the nucleus accumbens core and shell in the promotion and inhibition of actions during active and inhibitory avoidance.
Abstract The flexible implementation of active and passive strategies to avoid danger is critical to survival. Conversely, the inappropriate allocation of these behaviors may underlie pathological avoidance in neuropsychiatric illnesses. The present study investigated whether these two poles of avoidance may be differentially regulated by subdivsions of the nucleus accumbens, the core (NAcC) and shell (NAcS), which are known to bi-directionally control flexible action selection during reward-seeking. In so doing, we developed a novel cued active/inhibitory avoidance task conducted in operant chambers that entailed...
Source: Neuropharmacology - May 22, 2018 Category: Drugs & Pharmacology Authors: Piantadosi PT, Yeates DCM, Floresco SB Tags: Neuropharmacology Source Type: research

Altered brain activity during withdrawal from chronic alcohol is associated with changes in IL-6 signal transduction and GABAergic mechanisms in transgenic mice with increased astrocyte expression of IL-6.
Abstract Interleukin-6 (IL-6) is an important neuroimmune factor that is increased in the brain by alcohol exposure/withdrawal and is thought to play a role in the actions of alcohol on the brain. To gain insight into IL-6/alcohol/withdrawal interactions and how these interactions affect the brain, we are studying the effects of chronic binge alcohol exposure on transgenic mice that express elevated levels of IL-6 in the brain due to increased astrocyte expression (IL-6 tg) and their non-transgenic (non-tg) littermate controls. IL-6/alcohol/withdrawal interactions were identified by genotypic differences in sponta...
Source: Neuropharmacology - May 19, 2018 Category: Drugs & Pharmacology Authors: Gruol DL, Huitron-Resendiz S, Roberts AJ Tags: Neuropharmacology Source Type: research

Are Alzheimer's disease and other neurodegenerative disorders caused by impaired signalling of insulin and other hormones?
ST PMID: 29782874 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 18, 2018 Category: Drugs & Pharmacology Authors: Hölscher C, De Felice FG, Greig N, Ferreira ST Tags: Neuropharmacology Source Type: research

A tribute to Norman G Bowery.
PMID: 29782875 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 18, 2018 Category: Drugs & Pharmacology Authors: Bettler B, Crunelli V, Enna SJ Tags: Neuropharmacology Source Type: research

Chloride cotransporter KCC2 is essential for GABAergic inhibition in the SCN.
This study investigates the role of KCC2 on GABA-induced Ca2+ transients in SCN neurons from mice exposed to different photoperiods. We show for the first time that blocking KCC2 with the newly developed blocker ML077 can cause a shift in the polarity of the GABAergic response. This will increase the amount of excitatory responses in SCN neurons and thus cause a shift in excitatory/inhibitory ratio. These results indicate that KCC2 is an essential component in regulating [Cl-]i and the equilibrium potential of Cl- and thereby determining the sign of the GABAergic response. Moreover, our data suggest a role for the Cl- cotr...
Source: Neuropharmacology - May 18, 2018 Category: Drugs & Pharmacology Authors: Olde Engberink AHO, Meijer JH, Michel S Tags: Neuropharmacology Source Type: research

Activation and blockade of basolateral amygdala 5-HT6 receptor produce anxiolytic-like behaviors in an experimental model of Parkinson's disease.
Abstract Although the basolateral amygdala (BLA) and serotonin6 (5-HT6) receptor are involved in modulation of anxiety, their roles in Parkinson' disease (PD)-related anxiety are still unknown. Thus we perform this study to examine the involvement of BLA 5-HT6 receptor on anxiety in unilateral 6-hydroxydopamine-induced PD rats. The lesion of the medial forebrain bundle (MFB) induced anxiety-like behaviors, and decreased the basal firing rate of BLA glutamate neurons and dopamine (DA) levels in tissues of the medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip) in rats. Activation of BLA...
Source: Neuropharmacology - May 17, 2018 Category: Drugs & Pharmacology Authors: Sun YN, Yao L, Li LB, Wang Y, Du CX, Guo Y, Liu J Tags: Neuropharmacology Source Type: research

Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice.
Abstract The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence. In addition, cannabinoid receptor 2 has been found ex...
Source: Neuropharmacology - May 16, 2018 Category: Drugs & Pharmacology Authors: Frontera JL, Gonzalez Pini VM, Messore FL, Brusco A Tags: Neuropharmacology Source Type: research

Synaptic transmission and excitability during hypoxia with inflammation and reoxygenation in hippocampal CA1 neurons.
Abstract Although a number of experimental and clinical studies have shown that hypoxia typically accompanies acute inflammatory responses, the combinatorial effect of the two insults on basic neural function has not been thoroughly investigated. Previous studies have predominantly suggested that hypoxia reduces network activity; however, several studies suggest the opposite effect. Of note, inflammation is known to increase neural activity. In the current study, we examined the effects of limited oxygen in combination with an inflammatory stimulus, as well as the effects of reoxygenation, on synaptic transmission...
Source: Neuropharmacology - May 15, 2018 Category: Drugs & Pharmacology Authors: Yang YS, Son SJ, Choi JH, Rah JC Tags: Neuropharmacology Source Type: research

Identification and validation of midbrain Kcnq4 regulation of heavy alcohol consumption in rodents.
Abstract Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode KV7 channels influence alcohol intake and dependence. KV7 channels are a class of slowly activating voltage-dependent K+ channels that regulate neuronal excitability. Studies indicate that the KV7 channel positive modulator retigabine can decrease dopaminergic neuron firing, alter dopamine (DA) release, and reduce alcohol intake in heavy drinking rodents....
Source: Neuropharmacology - May 15, 2018 Category: Drugs & Pharmacology Authors: McGuier NS, Rinker JA, Cannady R, Fulmer DB, Jones SR, Hoffman M, Mulholland PJ Tags: Neuropharmacology Source Type: research

Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac.
ela L Abstract Striatal cholinergic interneurons provide modulation to striatal circuits involved in voluntary motor control and goal-directed behaviors through their autonomous tonic discharge and their firing "pause" responses to novel and rewarding environmental events. Striatal cholinergic interneuron hyperactivity was linked to the motor deficits associated with Parkinson's disease and the adverse effects of chronic antiparkinsonian therapy like l-DOPA-induced dyskinesia. Here we addressed whether Kv7 channels, which provide negative feedback to excitation in other neuron types, are involved in the ...
Source: Neuropharmacology - May 11, 2018 Category: Drugs & Pharmacology Authors: Paz RM, Tubert C, Stahl A, Díaz AL, Etchenique R, Murer MG, Rela L Tags: Neuropharmacology Source Type: research

The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act.
CONCLUSIONS: (1) psilocybin has an abuse potential appropriate for CSA scheduling if approved as medicine; (2) psilocybin can provide therapeutic benefits that may support the development of an approvable New Drug Application (NDA) but further studies are required which this review describes; (3) adverse effects of medical psilocybin are relatively low and manageable when administered according to risk management approaches; and (4) although further study is required, this review suggests that placement in Schedule IV may be appropriate if a psilocybin-containing medicine is approved. PMID: 29753748 [PubMed - as suppl...
Source: Neuropharmacology - May 10, 2018 Category: Drugs & Pharmacology Authors: Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE Tags: Neuropharmacology Source Type: research

Pharmacological inhibition of Receptor Protein Tyrosine Phosphatase β/ζ (PTPRZ1) modulates behavioral responses to ethanol.
Pharmacological inhibition of Receptor Protein Tyrosine Phosphatase β/ζ (PTPRZ1) modulates behavioral responses to ethanol. Neuropharmacology. 2018 May 09;137:86-95 Authors: Fernández-Calle R, Vicente-Rodríguez M, Pastor M, Gramage E, Di Geronimo B, Zapico JM, Coderch C, Pérez-García C, Lasek AW, de Pascual-Teresa B, Ramos A, Herradón G Abstract Pleiotrophin (PTN) and Midkine (MK) are neurotrophic factors that are upregulated in the prefrontal cortex after alcohol administration and have been shown to reduce ethanol drinking and reward. PTN and MK are the e...
Source: Neuropharmacology - May 9, 2018 Category: Drugs & Pharmacology Authors: Fernández-Calle R, Vicente-Rodríguez M, Pastor M, Gramage E, Di Geronimo B, Zapico JM, Coderch C, Pérez-García C, Lasek AW, de Pascual-Teresa B, Ramos A, Herradón G Tags: Neuropharmacology Source Type: research

Ketamine facilitates extinction of avoidance behavior and enhances synaptic plasticity in a rat model of anxiety vulnerability: Implications for the pathophysiology and treatment of anxiety disorders.
Abstract Anxiety disorders and posttraumatic stress disorder (PTSD) share a common feature of pathological avoidance behavior. The Wistar Kyoto (WKY) rat has been used as a model of anxiety vulnerability, expressing a behaviorally inhibited temperament, acquiring avoidance behavior more rapidly and displaying extinction-resistant avoidance compared to Sprague Dawley (SD) rats. Subanesthetic levels of ketamine have gained attention as a rapid antidepressant in treatment-resistant depression. While traditional antidepressants are commonly used to treat anxiety disorders and PTSD, the therapeutic utility of ketamine ...
Source: Neuropharmacology - May 8, 2018 Category: Drugs & Pharmacology Authors: Fortress AM, Smith IM, Pang KCH Tags: Neuropharmacology Source Type: research

5-HT1A receptor stimulation in the medial prefrontal cortex mediates the antidepressant effects of mGlu2/3 receptor antagonist in mice.
Abstract We previously reported that serotonergic transmission is involved in the antidepressant effects of metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists. However, the detailed underlying mechanisms had not yet been explored. In the present study, we investigated the role of the 5-HT1A receptor and its signaling cascade in the medial prefrontal cortex (mPFC) in the antidepressant effects of LY341495, an mGlu2/3 receptor antagonist. LY341495 significantly reduced the immobility time in the forced swimming test which sustained for 24 h after administration. The antidepressant effect of LY341495 was ...
Source: Neuropharmacology - May 5, 2018 Category: Drugs & Pharmacology Authors: Fukumoto K, Iijima M, Funakoshi T, Chaki S Tags: Neuropharmacology Source Type: research

Intermittent streptozotocin administration induces behavioral and pathological features relevant to Alzheimer's disease and vascular dementia.
CONCLUSIONS: STZ-treated animals exhibit cognitive deficits and histopathological changes seen in dementia. This model of dementia warrants continued investigation to better understand the role that DM plays in dementia-related alterations. PMID: 29738850 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 5, 2018 Category: Drugs & Pharmacology Authors: Murtishaw AS, Heaney CF, Bolton MM, Belmonte KCD, Langhardt MA, Kinney JW Tags: Neuropharmacology Source Type: research

Intranasally delivered small interfering RNA-mediated suppression of scavenger receptor Mac-1 attenuates microglial phenotype switching and working memory impairment following hypoxia.
Abstract Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of ...
Source: Neuropharmacology - May 5, 2018 Category: Drugs & Pharmacology Authors: Das S, Mishra KP, Ganju L, Singh SB Tags: Neuropharmacology Source Type: research

Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone.
Abstract Among cathinone drugs known as bath salts, methylenedioxypyrovalerone (MDPV) exerts its potent actions via the dopamine (DA) system, and at intoxicating doses may produce adverse behavioral effects. Previous work by our group suggests that prolonged alterations in correlated neural activity between cortical and striatal areas could underlie, at least in part, the adverse reactions to this bath salt drug. In the present study, we assessed the effect of acute MDPV administration on brain functional connectivity at 1 and 24 h in rats. Using graph theory metrics to assess in vivo brain functional network or...
Source: Neuropharmacology - May 3, 2018 Category: Drugs & Pharmacology Authors: Colon-Perez LM, Pino JA, Saha K, Pompilus M, Kaplitz S, Choudhury N, Jagnarine DA, Geste JR, Levin BA, Wilks I, Setlow B, Bruijnzeel AW, Khoshbouei H, Torres GE, Febo M Tags: Neuropharmacology Source Type: research

BDNF contributes to the neonatal incision-induced facilitation of spinal long-term potentiation and the exacerbation of incisional pain in adult rats.
In conclusion, spinal BDNF, at least partly derived from microglia, contributes to the neonatal incision-induced facilitation of spinal LTP and to the exacerbation of incisional pain in adult rats. Thus, spinal BDNF may combine the changes of microglial reactivity and synaptic plasticity in nIN-IN rats. PMID: 29729892 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 3, 2018 Category: Drugs & Pharmacology Authors: Ding X, Liang YJ, Su L, Liao FF, Fang D, Tai J, Xing GG Tags: Neuropharmacology Source Type: research

Memantine ameliorates depressive-like behaviors by regulating hippocampal cell proliferation and neuroprotection in olfactory bulbectomized mice.
Abstract Our previous study suggested that the non-competitive N-methyl-d-aspartate receptor antagonist memantine (MEM) inhibits dopamine (DA) reuptake and turnover by inhibiting brain monoamine oxidase. Clinical studies have reported that MEM may improve depressive symptoms; however, specific mechanisms underlying this effect are unclear. We performed emotional behavior, tail suspension, and forced swimming tests to examine whether MEM has antidepressant effects in olfactory bulbectomized (OBX) mice, an animal model of depression. Subsequently, we investigated the effects of MEM on the distribution of tyrosine hy...
Source: Neuropharmacology - May 3, 2018 Category: Drugs & Pharmacology Authors: Takahashi K, Nakagawasai O, Nemoto W, Kadota S, Isono J, Odaira T, Sakuma W, Arai Y, Tadano T, Tan-No K Tags: Neuropharmacology Source Type: research

Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects.
Abstract Expression of the catechol-O-methyl transferase (COMT) gene mainly determines prefrontal dopaminergic availability. Deficient prefrontal dopaminergic activity leads to loss of interest, energy, and motivation, which are core symptoms of depression. Given the role of stress-environmental interactions in major depressive disorder (MDD), we investigated the impact of COMT gene methylation status on prefrontal connectivity. We measured COMT gene methylation and polymorphisms (Val158Met) at the rs4468 locus in peripheral blood samples of healthy controls (n = 90) and patients with MDD (n = 90). We used...
Source: Neuropharmacology - April 30, 2018 Category: Drugs & Pharmacology Authors: Na KS, Won E, Kang J, Kim A, Choi S, Tae WS, Kim YK, Lee MS, Joe SH, Ham BJ Tags: Neuropharmacology Source Type: research

TNF α-dependent anhedonia and upregulation of hippocampal serotonin transporter activity in a mouse model of collagen-induced arthritis.
TNFα-dependent anhedonia and upregulation of hippocampal serotonin transporter activity in a mouse model of collagen-induced arthritis. Neuropharmacology. 2018 Apr 30;: Authors: Brown E, Mc Veigh CJ, Santos L, Gogarty M, Müller HK, Elfving B, Brayden DJ, Haase J Abstract The serotonin transporter (SERT) facilitates high affinity reuptake of 5-HT from the extracellular fluid and dysregulation of transporter function has been implicated in a range of mood disorders including depression. Recent studies have linked immune system activation to depression as well as to altered serotonin transport...
Source: Neuropharmacology - April 30, 2018 Category: Drugs & Pharmacology Authors: Brown E, Mc Veigh CJ, Santos L, Gogarty M, Müller HK, Elfving B, Brayden DJ, Haase J Tags: Neuropharmacology Source Type: research

Inhibition of miR-21 ameliorates excessive astrocyte activation and promotes axon regeneration following optic nerve crush.
This study's results suggest that miR-21 may represent a therapeutic target for optic nerve injury. PMID: 29709341 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - April 27, 2018 Category: Drugs & Pharmacology Authors: Li HJ, Pan YB, Sun ZL, Sun YY, Yang XT, Feng DF Tags: Neuropharmacology Source Type: research

Intermittent stimulation in the nucleus basalis of meynert improves sustained attention in rhesus monkeys.
In this study, we tested a novel method of improving sustained attention. Monkeys were engaged in a continuous performance task (CPT) while the nucleus basalis of Meynert (NB), the main source of cholinergic innervation of the neocortex, was stimulated. Intermittent NB stimulation improved the animals' performance by increasing the hit rate and decreasing the false alarm rate. Administration of the cholinesterase inhibitor donepezil or the muscarinic antagonist scopolamine alone impaired performance, whereas the nicotinic antagonist mecamylamine alone improved performance. Applying NB stimulation while mecamylamine or done...
Source: Neuropharmacology - April 26, 2018 Category: Drugs & Pharmacology Authors: Liu R, Crawford J, Callahan PM, Terry AV, Constantinidis C, Blake DT Tags: Neuropharmacology Source Type: research

Temporally dissociable effects of ketamine on neuronal discharge and gamma oscillations in rat thalamo-cortical networks.
CONCLUSIONS: As observed for PCP, ketamine markedly inhibited the activity of RtN neurons. However, unlike PCP, this effect did not translate into a disinhibition of MD/CM and mPFC excitatory neurons, possibly due to a more potent and simultaneous blockade of NMDA-Rs by ketamine in MD/CM and mPFC neurons. Hence, the present in vivo results show that ketamine evokes an early transient inhibition of neuronal discharge in thalamo-cortical networks, following its rapid pharmacokinetics, which is likely associated to its psychotomimetic effects. The prolonged increase in gamma oscillations may underlie its antidepressant action...
Source: Neuropharmacology - April 24, 2018 Category: Drugs & Pharmacology Authors: Amat-Foraster M, Jensen AA, Plath N, Herrik KF, Celada P, Artigas F Tags: Neuropharmacology Source Type: research

Fibroblast growth factor 20 is protective towards dopaminergic neurons in vivo in a paracrine manner.
In conclusion, FGF20 protects dopaminergic neurons in vivo, an action likely mediated through activation of FGFRs1, 3 or 4 found on these neurons. Given FGF20 is localised to astrocytes in the adult SN, endogenous FGF20 provides its protection of dopamine neurons through a paracrine action. Boosting the endogenous FGF20 production might offer potential as a future therapeutic strategy in Parkinson's disease. PMID: 29698669 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - April 23, 2018 Category: Drugs & Pharmacology Authors: Boshoff EL, Fletcher EJR, Duty S Tags: Neuropharmacology Source Type: research

Effects of monoamines on the intrinsic excitability of lateral orbitofrontal cortex neurons in alcohol-dependent and non-dependent female mice.
Abstract Changes in brain reward and control systems of frontal cortical areas including the orbitofrontal cortex (OFC) are associated with alcohol use disorders (AUD). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including AUDs. Recent findings from this laboratory demonstrate that D2, α2-adrenergic and 5HT1A receptors all decrease the intrinsic excitability of lateral OFC (lOFC) neurons in naïve male mice and that this effect is lost in mice exposed to repeated cycles of chronic intermittent et...
Source: Neuropharmacology - April 21, 2018 Category: Drugs & Pharmacology Authors: Nimitvilai S, Lopez MF, Woodward JJ Tags: Neuropharmacology Source Type: research

Changes in the hippocampal and peripheral phospholipid profiles are associated with neurodegeneration hallmarks in a long-term global cerebral ischemia model: Attenuation by Linalool.
In this study, we analyzed changes in the central and peripheral phospholipid profiles in ischemic rats and determined whether a protective monoterpene, Linalool, could modify them. We used an in vitro model of glutamate (125 μM) excitotoxicity and an in vivo global ischemia model in Wistar rats. Linalool (0.1 μM) protected neurons and astrocytes by reducing LDH release and restoring ATP levels. Linalool was administered orally at a dose of 25 mg/kg every 24 h for a month, behavioral tests were performed, and a lipidomic analysis was conducted using mass spectrometry. Animals treated with Linalool displayed f...
Source: Neuropharmacology - April 19, 2018 Category: Drugs & Pharmacology Authors: Sabogal-Guáqueta AM, Posada-Duque R, Cortes NC, Arias-Londoño JD, Cardona-Gómez GP Tags: Neuropharmacology Source Type: research

Neuroendocrine response to GABA-B receptor agonism in alcohol-dependent individuals: Results from a combined outpatient and human laboratory experiment.
Abstract Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the nervous system, plays an important role in biobehavioral processes that regulate alcohol seeking, food intake, and stress response. The metabotropic GABA-B receptor has been investigated as a potential therapeutic target for alcohol use disorder, by using orthosteric agonists (e.g., baclofen) and positive allosteric modulators. Whether and how pharmacological manipulation of the GABA-B receptor, in combination with alcohol intake, may affect feeding- and stress-related neuroendocrine pathways remains unknown. In the present random...
Source: Neuropharmacology - April 14, 2018 Category: Drugs & Pharmacology Authors: Farokhnia M, Sheskier MB, Lee MR, Le AN, Singley E, Bouhlal S, Ton T, Zhao Z, Leggio L Tags: Neuropharmacology Source Type: research