No abstract

Background and Purpose: Muscarinic acetylcholine receptors mediate alcohol consumption and seeking in rats. While M 4 and M 5 receptors have recently been implicated to mediate these behaviours in the striatum, their role in other brain regions remain unknown. The ventral tegmental area (VTA) and ventral subiculum (vSub) both densely express M 4 and M 5 receptors and modulate alcohol-seeking, via their projections to the nucleus accumbens shell (AcbSh). Experimental Approach: In Indiana alcohol-preferring (iP) male rats, we examined Chrm4 (M 4 ) and Chrm5 (M 5 ) expression in the VTA and vSub following long-term alcohol consumption and abstinence using RT-qPCR. Using a combination of retrograde tracing and RNAscope, we examined the localisation of Chrm4 and Chrm5 on vSub cells that project to the AcbSh. Using selective allosteric modulators, we examined the functional role of M 4 and M 5 receptors within the vSub in alcohol consumption, context-induced alcohol-seeking, locomotor activity, and food/water consumption.

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