Recent findings in adolescent models emphasize that the contributions of other neurotransmitters to reward systems should not be overlooked. Glutamatergic, cholinergic, and opioidergic pathways each play important roles in regulating the dopaminergic reward system [30,33]. In rodents, repeated ethanol exposure reduces hippocampal glutamate dehydrogenase 1 and phosphorylation of the NR2B subunit of glutamatergic N-methyl-d-aspartate receptors in the frontal cortex, hippocampus, and nucleus accumbens of adolescent, but not adult rats [31,34]. These changes within reward neurocircuitry support the idea that alcohol-mediated changes in glutamatergic neurotransmission during adolescence may contribute to the development of an AUD [35]. Further, blockade of μ-opioid receptors inhibits alcohol-mediated social facilitation in adolescent rats, which links the endogenous opioid system to rewarding effects of alcohol in this age group [36]. Alcohol also enhances midbrain choline acetyltransferase activity in adolescent mice, suggesting that alcohol increases midbrain cholinergic innervation [37]. This could have important consequences for reward since ventral tegmental acetylcholine is required for alcohol-induced dopamine release into the nucleus accumbens [30]. Potential interactions between these neurotransmitter systems warrant further study as they could hold important clues regarding the enhanced sensitivity of the adolescent reward response to alcohol.
