Acetaldehyde Oral Self-Administration: Evidence from the Operant-Conflict Paradigm

Background: Acetaldehyde (ACD), ethanol's first metabolite, has been reported to interact with the dopaminergic reward system, and with the neural circuits involved in stress response. Rats self-administer ACD directly into cerebral ventricles, and multiple intracerebroventricular infusions of ACD produce conditioned place preference. Self-administration has been largely employed to assess the reinforcing and addictive properties of most drugs of abuse. In particular, operant conditioning is a valid model to investigate drug-seeking and drug-taking behavior in rats. Methods: This study was aimed at the evaluation of (i) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behavior; (ii) ACD effect in a conflict situation employing the punishment-based GellerSeifter procedure; and (iii) the onset of a relapse drinking behavior, following ACD deprivation. The lever-pressing procedure in a sound-attenuated operant-conditioning chamber was scheduled into 3 different periods: (i) trainingrewarded responses with a fixed ratio 1; (ii) conflictrewarded responses periodically associated with a 0.2 mA foot-shock; and (iii) relapserewarded lever presses following 1-week ACD abstinence. Results: Our results show that oral self-administrated ACD induced: a higher rate of punished responses in GellerSeifter procedures; and the establishment of a relapse behavior following ACD deprivation. Conclusions: In conclusion, our results indicate that ACD is able to induce an operant-drinking behavior, which is also maintained besides the conflict procedure and enhanced by the deprivation effect, supporting the hypothesis that ACD itself possesses motivational properties, such as alcohol and other substances of abuse.