Subregion and sex differences in ethanol activation of cholinergic and glutamatergic cells in the mesopontine tegmentum

Abstract

Ethanol engages cholinergic signaling and elicits endogenous acetylcholine release. Acetylcholine input to the midbrain originates from the mesopontine tegmentum (MPT), which is composed of the laterodorsal tegmentum (LDT) and the pedunculopontine tegmental nucleus (PPN). We investigated the effect of acute and chronic ethanol administration on cholinergic and glutamatergic neuron activation in the PPN and LDT in male and female mice. We show that ethanol activates neurons of the PPN and not the LDT in male mice. Chronic 15 daily injections of 2 g/kg ethanol induced Fos expression in cholinergic and glutamatergic PPN neurons in male mice, whereas ethanol did not increase cholinergic and glutamatergic neuronal activation in the LDT. A single acute 4 g/kg injection, but not a single 2 g/kg injection, induced cholinergic neuron activation in the male PPN but not the LDT. In contrast, acute or chronic ethanol at either dose or duration had no effect on the activation of cholinergic or glutamatergic neurons in the MPT of female mice. Female mice had higher baseline level of activation in cholinergic neurons compared with males. We also found a population of co-labeled cholinergic and glutamatergic neurons in the PPN and LDT which were highly active in the saline- and ethanol-treated groups in both sexes. These findings illustrate the complex differential effects of ethanol across dose, time point, MPT subregion and sex.