¹The University of Melbourne, The Florey, Melbourne, Australia

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.