We found decreases in the expression of many cholinergic-specific genes including ChAT, as well as all 5 subtypes of the muscarinic cholinergic receptors measured in young adult mice following adolescent binge treatment. Post-mortem brains from humans with alcohol use disorder have fewer muscarinic receptors and other cholinergic markers in hippocampus (Freund and Ballinger, 1989a; Nordberg et al., 1983) and cerebral cortex (Freund and Ballinger, 1989b). Adolescent binge treatment of rats has been shown to disrupt adult sleep and electrophysiology consistent with altered cholinergic systems (Ehlers and Criado, 2010). In adult rats, 28 weeks of alcohol treatment results in a progressive and persistent loss of 60-80% of multiple induces of forebrain cholinergic neurons (Arendt et al., 1995; Arendt et al., 1988b) that are associated with memory impairments (Arendt et al., 1988a). After 8 weeks of ethanol treatment in adult rats, full recovery of reductions in ChAT activity was observed in the basal forebrain during 4 weeks of abstinence (Arendt et al., 1989). We found reduced forebrain histological area and cholinergic neuron density in young adult mice following adolescent binge treatment for only 10 days, with no evidence of recovery from gene array or immunohistochemistry.
