The galanin-3 receptor antagonist, SNAP 37889, suppresses alcohol drinking and morphine self-administration in mice

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Abstract

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 (GAL3) specifically regulates emotional states and plays a role in motivation, reward and drug-seeking behaviour. We have previously shown that the GAL3 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 GAL3 signalling. This study implicates the GAL3 receptor in consummatory drive which may have wider implications for the treatment of different addictions.

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