555. M4 MUSCARINIC RECEPTOR ACTIVATION IN THE CENTRAL AMYGDALA REDUCES STRESS-INDUCED ALCOHOL SEEKING IN ALCOHOL PREFERRING RATS

Abstract Background Stress is a key factor contributing to relapse, a major hurdle in the treatment of alcohol use disorders. A region key to brain stress systems and essential for emotional regulation is the central amygdala, and alcohol dependence has been shown to impact this brain region functioning. Muscarinic acetylcholine receptors (mAChRs) mediate alcohol consumption and seeking and are densely expressed in the central amygdala. Targeting M1 and M4 mAChRs have been highlighted as potential novel treatment targets for alcohol use disorders. Aims & Objectives To probe the potential role of muscarinic receptors in the central amygdala in stress-induced relapse to alcohol seeking. Method We employed quantitative polymerase chain reaction (qPCR) of central amygdala following abstinence from chronic alcohol drinking in iP alcohol preferring rats. In a different cohort of rats, we pharmacologically activated M4 mAChR with the selective positive allosteric modulator, VU0467154 (VU154), both systemically (30 mg/kg, i.p) and intra-central amygdala (3μmol/hemisphere), during a stress-induced relapse behavioural paradigm. Results Our qPCR data show a downregulation of M1 and M4 mRNA in the central amygdala following abstinence from chronic alcohol drinking. Further, both systemic and intra-central amygdala VU154 administration reduced stress-induced alcohol-seeking. Discussion & Conclusions Collectively, our data show alcohol-induced cholinergic dysregulation in the central amygdala and a role for M4 mAChR within this brain region in reducing relapse to alcohol seeking.