Dopamine concentrations in the nucleus accumbens core-shell border during the early stages of operant ethanol self-administration

Mesolimbic dopamine plays an important role in ethanol reinforcement, and studies have shown that accumbal dopamine increases during operant ethanol self-administration. However, no one has ever studied this dopaminergic response during the acquisition of ethanol self-administration. Furthermore, some studies have shown that the dopamine signal does not correlate with the pharmacological effects of ethanol, but with the time during which the animal consumes the majority of the ethanol solution and when the sensory stimuli of ethanol are strongest. However, there is currently no direct evidence showing that the sensory stimuli of ethanol is indeed what causes the brief increase in accumbal dopamine during ethanol self-administration. The studies in this dissertation attempted to elucidate these issues. We designed and tested a placebo spout, which was to be used to study the relationship between accumbal dopamine and the sensory stimuli of ethanol during self-administration. Unfortunately, the placebo designs were either not feasible for performing microdialysis or did not show promising behavioral data. We also developed and tested a self-administration protocol in which the concentrations of ethanol (10%) were kept constant throughout the study. The new protocol was successful in initiating and maintaining ethanol self-administration, and the animals doubled their intake from day 1 to day 2 of ethanol consumption. Using this protocol, we trained male Long Evans rats to self-administer ethanol and measured accumbal dopamine during the first two days of ethanol self-administration through microdialysis. The behavioral and neurochemical data matched. A single exposure to ethanol was sufficient for the animals to double their ethanol consumption by day 2 and to cause an increase in accumbal dopamine during the first 5 minutes of ethanol self-administration. The dopamine response was observed during the time when the sensory stimuli of ethanol were strongest, but before ethanol reached peak concentrations in the brain. Overall, these results suggest that the dopamine response to ethanol self-administration may not be solely pharmacological and that a single exposure to ethanol is sufficient to learn the association between ethanol and its cues. These findings give us greater insight into mesolimbic dopamine's role in the early stages of ethanol reinforcement.