Voluntary adolescent drinking enhances excitation by low levels of alcohol in a subset of dopaminergic neurons in the ventral tegmental area

Abstract

Enhanced dopamine (DA) neurotransmission from the ventral tegmental area (VTA) to the ventral striatum is thought to drive drug self-administration and mediate positive reinforcement. We examined neuronal firing rates in slices of mouse midbrain following adolescent binge-like alcohol drinking and find that prior alcohol experience greatly enhanced the sensitivity to excitation by ethanol itself (10–50 mM) in a subset of ventral midbrain DA neurons located in the medial VTA. This enhanced response after drinking was not associated with alterations of firing rate or other measures of intrinsic excitability. In addition, the phenomenon appears to be specific to adolescent drinking, as mice that established a drinking preference only after the onset of adulthood showed no change in alcohol sensitivity. Here we demonstrate not only that drinking during adolescence induces enhanced alcohol sensitivity, but also that this DA neuronal response occurs over a range of alcohol concentrations associated with social drinking in humans.

Effects of acute alcohol on excitability in the CNS

“…A history of alcohol exposure has been shown to be important in the medial VTA. In brain slices obtained from mice given intermittent access to alcohol during adolescence (PD30–60), 10 mM ethanol has been shown to increase the firing rate of DA neurons in the medial VTA 7.7%, whereas no effect was seen in brain slices from alcohol-naïve mice [24]. While 20 mM ethanol has been found to increase the firing rate of VTA DA neurons in the rat, the firing rates of VTA GABA neurons have been found to decrease by 41% at this concentration [25].…”

Addictive neurons

“…WIN increased the basal spontaneous frequency from ~3 to 5 Hz. The spike frequency in VTA DA neurons of male rats is similar to those of mice (~3 Hz) of the same gender at P60 [22] . Voluntary drinking in these adolescent males did not alter spike rates.…”

“…Since VTA in rodents and monkeys has no clear borders (Figure 1 and 2) as a nucleus unlike the amygdala, hippocampus and septum, defining DA neurons would be always 'somewhat misleading' by any criteria [22] . Therefore, also previous studies in rats observed heterogeneities in spike properties and when possible have classified them as type 1 or 2 [24] .…”

Adolescent Intermittent Ethanol Increases the Sensitivity to the Reinforcing Properties of Ethanol and the Expression of Select Cholinergic and Dopaminergic Genes within the Posterior Ventral Tegmental Area

“…Selective activation of α 7 nAchR results in the release of glutamate in the VTA, which, if paired with postsynaptic depolarization, results in long‐term potentiation in VTA DA neurons (Mansvelder and McGehee, ). In mice, adolescent alcohol consumption increases the sensitivity in select VTA DA neurons to become activated by low concentrations of EtOH (Avegno et al., ). Indirect evidence suggests that these hypersensitive DA neurons produced by adolescent EtOH consumption contain α 7 nAchRs and may be the subset of VTA neurons that coexpress DA and glutamate (Avegno et al., ).…”