Role of acetaldehyde in the rewarding effects of ethanol ingestion: a conditioned place-preference study in the rats

Acetaldehyde (ACD), the first product of ethanol (ETOH) metabolism, has been speculated to be involved in many behavioral effects of ETOH. Different studies showed that ACD is self-administered into to the ventricular system of the brain and into the ventral tegmental area by laboratory rats, suggesting that ACD possesses reinforcing properties. In support of this notion, it has been shown that rats would display a positive place conditioning after intracerebro- ventricular infusions or after intraperitoneal injection of ACD leading to the hypothesis that this drug (alone or acting in synergism with ETOH) might play a role in the behavioural effects of ETOH and possibly in its hedonistic effects. However, the role of ETOH-formed ACD is still unclear in the rewarding effects of ETOH ingested. Since a large quantity of ETOH ingested (between 90-98%) is metabolised into ACD we decided to investigate the possible basis of the reinforcing effects of ACD ingestion (10, 20 and 40 mg/kg, i.g.) and the relationships between the rewarding properties of ETOH (0.5, 1, and 2 g/kg, i.g.), by the use of the conditioned place preference (cpp). Further, in order to ascertain if ACD is mainly involved in the reinforcing effects of ETOH ingestion we used a competitive inhibitor of alchol dehydrogenase ADH, 4-methylpyrazole (4-MP) (90 mg/kg i.p.), administered at alternate days during the conditioning trial. The present results show that ACD administered by i.g. induces cpp at the dose of 20 mg/kg. Moreover, the effect of 1g/kg i.g. of ETOH-induced cpp is blocked by pharmacological prevention of ACD formation via administration of 4- MP. This observation is in line with recent in vivo electrophysiological data showing a reduction of the stimulating effect of ETOH on VTA DA neurones by pharmacological blockade of ETOH metabolism with 4-MP. Together, these results indicate that ACD has CNS effects in its own right and is involved in the ETOH-induced cpp.