L-cysteine reduces acquisition of oral ethanol self-administration and reinstatement of ethanol-seeking behavior in rats

Rationale: Previous findings indicated that acetaldehyde (ACD), the first metabolite of ethanol (EtOH) is involved in reinforcing effect of intragastric EtOH. Objectives: The aim of this study was to test the hypothesis that ACD could be involve in the acquisition and in the reinstatement of EtOH seeking behavior. Thus, we undertake a study using the L-cysteine, an ACD- sequestrating agent, during the acquisition and reinstatement phases of oral EtOH self-administration. Methods: Wistar rats were pretreated intraperitoneally with saline or L-cysteine (20-40 mg/kg), 30 min before each acquisition phase, in an operant nose-poking paradigm where they were given the opportunity to oral self-administer tap water (control) or EtOH (5-10% v/v). After acquisition (15 days), the EtOH groups, treated with saline or L-cysteine were tested on reinstatement (5 days) after EtOH extinction (5 days). Results: The animals that had access to EtOH solution showed rates of active nose pokes significantly higher than the control group and discriminated between the active and inactive nose pokes. Furthermore, rats self-administering EtOH (10%) also demonstrated extinction behavior and gradually reinstated active nose poke responding when EtOH was reintroduced. L-cysteine, dose dependently, reduced acquisition of oral EtOH self-administration and reinstatement after EtOH deprivation. Conclusions: The present results suggest that EtOH-derived ACD could be involved in the acquisition of oral EtOH self- administration and in the reinstatement of EtOH-seeking behavior. Thus, L- cysteine by sequestering EtOH-derived ACD, would deprive EtOH of its motivational properties and reduce its abuse liability.