The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats

Acetaldehyde (ACD), the first metabolite of ethanol, is a biologically active compound, which may mediate some of the reinforcing, behavioral and neurotoxic effects of ethanol. The objective of this study is to test the hypothesis that ACD is reinforcing with the mesolimbic system. The intracranial self-administration (ICSA) technique was employed to determine whether ACD was reinforcing in the posterior ventral tegmental areas (VTA), a site that supports the reinforcing actions of ethanol. Adult female alcohol-preferring (P) rats were implanted with guide cannulae aimed at the posterior VTA. Subjects were placed in two-lever operant chambers 7 - 10 days after surgery. Responding on the active lever on a fixed ratio 1 (FR1) schedule of reinforcement caused the delivery of 100 nl of infusate, whereas responses on the inactive lever were without consequences. Rats were assigned to one of five groups that self-administered either artificial cererbrospinal fluid (aCSF) throughout all eight sessions (4 h in duration) or 3- and 6-, 11- and 24-, 45- and 90- or 180- and 360-muM ACD for the eight sessions, with the lower concentration of ACD given for the initial four sessions and the higher concentration of ACD given to the last four sessions. A second experiment examined the acquisition (first four sessions), extinction (aCSF in sessions 5 and 6) and reinstatement using 90-muM ACD. Adult P rats readily self-administered 6-90-muM ACD and discriminated between the active and inactive levers. Furthermore, rats self-administering 90-muM ACD also demonstrated extinction behavior when a CSF was substituted for ACD and gradually reinstated active lever responding with ACD was reintroduced. P rats maintained similar numbers of infusions and infusion patterns under both time-out schedules. Overall, the data indicate the ACD is a potent reinforcer within the posterior VTA of the P rat. (C) 2002 Elsevier Science Inc. All rights reserved.