The neuropeptide, galanin, is widely expressed in the central and peripheral nervous systems and is involved in a range of different functions including nociception, neurogenesis, hormone release, reproduction, cognitive function and appetite. Given the overlap between galanin expression and reward circuitry in the brain, galanin has been targeted for alcohol use disorder (AUD) and opioid dependency. Furthermore, the galanin-3 receptor (GAL) specifically regulates emotional states and plays a role in motivation, reward and drug-seeking behaviour. We have previously shown that the GAL antagonist, SNAP 37889, reduces ethanol self-administration and cue-induced re-instatement in alcohol-preferring (iP) rats with no alterations in locomotor activity or anxiety-like behaviour. The aim of this study was to investigate whether SNAP 37889 reduces binge drinking and/or self-administration of morphine in mice. Using the Scheduled High Alcohol Consumption (SHAC) procedure, SNAP 37889 (30 mg/kg) treated mice drank significantly less ethanol, sucrose and saccharin than vehicle treated mice. Using an operant paradigm, SNAP 37889 reduced morphine self-administration but failed to impact cue-induced relapse-like behaviour. SNAP 37889 had no significant effect on locomotor activity, motor co-ordination, anxiety, nor was SNAP 37889 itself positively reinforcing. Liver assays showed that there was no alteration in the rate of hepatic ethanol metabolism between SNAP 37889 and vehicle treated mice suggesting that the reduction in ethanol intake via SNAP 37889 is due to a central effect of GAL signalling. This study implicates the GAL receptor in consummatory drive which may have wider implications for the treatment of different addictions.
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http://dx.doi.org/10.1016/j.neuropharm.2017.03.004 | DOI Listing |
Exp Neurol
December 2023
Institute of Physiology 1/Neurophysiology, Jena University Hospital, Jena D-07740, Germany. Electronic address:
The inhibitory neuropeptide Galanin (Gal) has been shown to mediate anticonvulsion and neuroprotection. Here we investigated whether Gal affects cortical spreading depolarization (CSD). CSD is considered the pathophysiological neuronal mechanism of migraine aura, and a neuronal mechanism aggravating brain damage upon afflictions of the brain.
View Article and Find Full Text PDFPharmacol Res
February 2023
Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA. Electronic address:
The neuropeptide galanin receptor 3 (GALR3) is a class A G protein-coupled receptor (GPCR) broadly expressed in the nervous system, including the retina. GALR3 is involved in the modulation of immune and inflammatory responses. Tight control of these processes is critical for maintaining homeostasis in the retina and is required to sustain vision.
View Article and Find Full Text PDFJ Biomol Struct Dyn
November 2021
Biopolymer Modelling Laboratory, Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.
Our present work studies the structure-based pharmacophore modeling and designing inhibitor against Gal3 receptor through molecular dynamics (MD) simulations extensively. Pharmacophore models play a key role in computer-aided drug discovery like in the case of virtual screening of chemical databases, drug design and lead optimization. Structure-based methods for developing pharmacophore models are important, and there have been a number of studies combining such methods with the use of MD simulations to model protein's flexibility.
View Article and Find Full Text PDFAm J Pathol
April 2019
State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address:
Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown.
View Article and Find Full Text PDFJ Psychopharmacol
August 2018
4 School of Life Sciences, La Trobe University, Melbourne, VIC, Australia.
Introduction: This study aimed to investigate the effects of the galanin-3 receptor antagonist, SNAP 37889, on c-Fos protein expression after cue-induced reinstatement of alcohol-seeking in the brains of alcohol-preferring rats.
Methods: Eighteen alcohol-preferring rats were trained to self-administer 10% v/v ethanol in the presence of response-contingent cues, which was followed by extinction. Rats were then treated with SNAP 37889 (30 mg/kg, i.
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