The effect of ethanol consumption on dopamine and ethanol concentrations in the nucleus accumbens during the development of reinforcement and the involvement of the k-Opioid receptor in the modulation of dopamine activity during ethanol self-administration

by Doyon, William Maurice

The present study was designed to clarify the role of dopamine in the nucleus accumbens during operant ethanol self-administration by separating bar pressing (ethanol seeking) from ethanol consumption. Furthermore, we sought to define the relationship between ethanol in the brain and the accumbal dopamine response after oral self-administration of ethanol. Two separate groups of male Long-Evans rats were trained to bar press using 10% ethanol or water and a procedure that distinguished between bar pressing and consumption of ethanol (or water). Rats were trained to elicit an escalating number of bar presses across daily sessions before gaining access to the drinking solution for 20 min. Microdialysis was performed before (during a waiting period), during and after bar pressing and drinking. A handling control group was included, but did not receive training. Dopamine and ethanol were analyzed from the dialysis samples. There was a significant increase in accumbal dopamine during 41 placement of the rats into the operant chamber in both trained rats and handling controls. The lever-pressing period did not produce an increase in dialysate dopamine. Accumbal dopamine was increased in the first 5 min of ethanol, but not water, consumption, followed by a return to baseline. Ethanol appeared in the dialysates in the first 5 min sample following ethanol availability, and peak concentrations were reached at 10 min. Most of the ethanol and water consumption occurred in the first 5 minutes after access to the solution. The probe placements were distributed in the core (32%), shell (32%), and core plus shell (36%) regions of the nucleus accumbens. The enhancement of dopamine activity during transfer into the operant chamber does not depend on anticipation or operant training using ethanol or water reinforcement. Furthermore, the difference between the time course of the accumbal dopamine response and ethanol in dialysates suggests that the dopamine response is not solely due to pharmacological effects of ethanol. Instead, the dopamine response may be associated with the stimulus properties of ethanol presentation, which would be strongest during consumption.