Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats

Abstract

Rationale Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. Objectives We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Methods Rats received intermittent intragastric ethanol, water or nothing during adolescence. In adulthood, electrically-evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Results Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50% in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. Conclusions The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats, and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age.

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

“…Properties of circuit function such as long-term potentiation, spontaneous interneuron firing, and alcoholinduced dopamine release in the NAc is impacted by adolescent alcohol exposure (Shnitko et al, 2016;Swartzwelder et al, 1995;Yan et al, 2010). Although the effects to neurons have been well characterized, much less is known about glial responses to alcohol during adolescence.…”

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect

“…The surgical and voltammetric procedure was as previously described (Robinson et al, 2005, Shnitko et al, 2016a). On postpartum day 1 – 3, rats were anesthetized (1.5 g/kg urethane, i.p.)…”

“…Electrochemical data were analyzed as previously described (Robinson et al, 2005, Shnitko et al, 2016a). Changes in current due to dopamine oxidation and reduction were identified in the voltammetric data by using color plots and cyclic voltammograms.…”

“…To investigate whether dopamine release and uptake parameters differed among virgin and postpartum groups, dopamine release and clearance were modeled as previously described (Shnitko et al, 2016a) using a Michaelis-Menten kinetic equation (Wu et al, 2001). This equation models electrically stimulated dopamine release as a function of the concentration of dopamine released per pulse of stimulation ([DA] p , nM), the frequency of electrical stimulation (f, Hz), the velocity of dopamine transporters (V max , nM/sec), and the affinity of those transporters (K m , nM).…”

In vivo voltammetric evidence that locus coeruleus activation predominantly releases norepinephrine in the infralimbic cortex: Effect of acute ethanol

“…In sharp contrast to DA, the effect of ethanol on NE release in different brain areas including the PFC was not previously explored with FSCV. The most consistent findings on DA are that acute ethanol administration decreases terminal DA release induced by electrical stimulation of the VTA in freely moving and anesthetized preparations (Budygin et al, 2001;Jones, Mathews, & Budygin, 2006;Schilaty et al, 2014;Shnitko, Spear, & Robinson, 2016). The mechanism of this ethanol action is unclear still.…”