Activity of orally self-administered acetaldehyde in an operant/conflict paradigm in rats; involvement of cannabinoid cb1 receptors

Acetaldehyde (ACD), ethanol first metabolite, interacts with the dopaminergic reward system, and with the neuropeptidergic transmission in the hypothalamus. Self-administration within operant conditioning is a valid model to investigate drug-seeking and drug-taking behaviour in rats. Cannabinoid CB1 receptors are involved in reinstatement of alcohol-seeking behaviour and of many other drugs of abuse (3). Accordingly, this study was aimed at the evaluation of: 1) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behaviour; 2) the onset of a relapse drinking behaviour, following ACD deprivation; 3) ACD effect in a conflict situation employing the punishment-based Geller-Seifter procedure; 4) the effect of CB1 antagonist AM-281 (1.5mg/Kg, i.p.) on ACD effects. The lever pressing procedure was scheduled into: training - rewarded responses with a FR1; extinction - no rewarded responses; relapse- following 1 week-deprivation; conflict - rewarded responses cyclically associated with a 0.2 mA footshock. Our results show that orally self-administrated ACD induced: a higher self-administration rate during the training period and an increase in the number of responses during extinction (p< 0.05); the establishment of a relapse behaviour following 7-day abstinence p< 0.001); an increase in the number of punished responses in the conflict phase (p< 0.001), with respect to controls. AM-281 was able to decrease the number of lever presses in ACD-drinking rats, during extinction (p< 0.05) and relapse (p< 0.001) compared to respective controls. This study shows for the first time that orally self-administered ACD acts as other substance of abuse: ACD is able to induce and maintain an operant drinking behaviour; ACD self-administration occurs even under aversive conditions; ACD induces a relapse behaviour after deprivation. We also indicate that ACD reinforcing properties involve CB1 receptor activity, suggesting that manipulation of the endocannabinoid system may be helpful in the treatment of alcohol addiction.