Dopamine increases in the nucleus accumbens after contingent and noncontingent ethanol administration in rats, but the contributions of the core, coreshell border, and shell subregions to this response are unclear. Also, it is not fully understood if increases in dopamine under these circumstances are due to the pharmacological effects of ethanol, stimuli associated with administration, or both. The studies presented in this dissertation were conducted to investigate dopamine’s role in each of these accumbal regions during ethanol administration and presentation of associated stimuli. Using microdialysis, ethanol and dopamine concentrations in accumbal subregions were measured every five minutes before, during, and after either experimenter-delivered intravenous ethanol or operant ethanol self-administration. After intravenous ethanol infusions, the increase in dopamine in the shell of the accumbens was significantly higher than that observed in the core. During operant ethanol self-administration, the core, core-shell border, and shell, all exhibited significant increases in dopamine during transfer of the animal into the operant chamber, with animals trained to drink sucrose + ethanol showing significantly higher increases when compared to those trained to drink sucrose alone. Dopamine increased significantly only in the core-shell border during ethanol consumption, and dopamine levels in the core and shell responded in a similar manner during all phases of the experiment. Together, these results suggest that dopamine responses to intravenous ethanol infusions and operant ethanol self-administration are subregion specific. Also, while increases in dopamine resulting from intravenous ethanol infusions in naïve animals appear to be due to the pharmacological effects of the drug, increases in ethanol-experienced animals during transfer into the operant chamber, and during ethanol consumption, may also be due to stimuli associated with ethanol administration. / text

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. / text