SY40-1
NEUROPEPTIDES AS THERAPEUTIC TARGETS FOR DRUG-SEEKING

Abstract

Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. Increasing our understanding of the brain circuits and chemicals that regulate alcohol intake and relapse offers the potential for more targeted therapeutic approaches to assist in relapse prevention. Stress is a key precipitant of relapse, and relaxin-3 signalling modulates stress responses and alcohol intake. We therefore tested whether RXFP3 antagonism in stress-related brain areas, such as the bed nucleus of the stria terminalis (BNST), modulated alcohol use and stress-induced alcohol-seeking. Rats were trained to self-administer ethanol (10% v/v) and then had intracerebral guide cannulae implanted into either the lateral ventricle or immediately above the BNST. Bilateral injections of the RXFP3 antagonist, R3 (B1-22) R (1 μg/0.5μl) into the BNST reduced ethanol self-administration. Reinstatement was performed following extinction after pre-treatment with yohimbine (1 mg/kg i.p.). Intracerebroventricular R3 (B1-22) R (10 μg/5μl) prevented stress-induced reinstatement of alcohol-seeking. Microinjection of R3 (B1-22)R in the BNST (1 μg/0.5μl bilaterally) markedly attenuated stress-induced reinstatement of alcohol-seeking. These data suggest the relaxin-3/RXFP3 system can modulate both alcohol consumption and stress-induced reinstatement of alcohol-seeking. In the case of relapse-like alcohol-seeking, this system appears particularly involved in stress-mediated relapse via actions within the BNST.