Ethanol self-infusion into the ventral tegmental area by alcohol-preferring rats

The ventral tegmental area (VTA) and its projections have been implicated in the reinforcing effects of drugs of abuse. Selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines of rats were used to evaluate the reinforcing actions of ethanol in the VTA using intracranial self-administration (ICSA) operant procedures. P rats self-administered nanoliter quantities of 50–200 mg% ethanol in artificial CSF directly into the VTA whereas NP rats had low levels of responding at these ethanol concentrations. Responses on the active lever were 50-fold higher for the P compared with the NP rats for the self-infusion of 150 mg% ethanol. NP rats responded at the same level on the active and inactive levers at all ethanol concentrations and had low responses/session (3 to 15 total responses) at all concentrations. Further, operant responding on the active lever was reduced when artificial CSF alone was substituted for 100 mg% ethanol, and responding on the active lever was reinstated when ethanol was returned. For one group of rats, an illuminated house light served as a discriminative stimulus, which signalled the availability of ICSA, while a cue light was paired with the onset of ethanol infusion. Extinction in the presence of these stimuli required 6–7 sessions. However, only 2–3 extinction sessions were necessary for another group trained without stimulus cues, suggesting that cues paired with the ICSA of ethanol can acquire conditioned reinforcing properties. The findings indicate that ethanol can act as a reinforcer when administered directly into the VTA. Furthermore, since ethanol maintained responding significantly more in the P than NP rat, the results suggest that the neurobiological substrates in the VTA, which subserve the reward-relevant actions of alcohol, may be genetically influenced.