Acetaldehyde as a drug of abuse: Involvement of endocannabinoid- and dopamine neurotransmission

Acetaldehyde (ACD), the first metabolite of ethanol, directly enhances dopamine neurotransmission (1) and has rewarding and motivational properties in paradigms tailored for studying addictive-like behaviours (2, 3). The endocannabinoid system affects distinct drug-related behaviours, since it may in turn fine-tune dopamine cell activity (4, 5). In light of this, the present study aimed at investigating the effects of a direct manipulation of the DAergic synapse, and the contribution of the endocannabinoid system on oral ACD self-administration in rats. ACD drinking-behaviour was evaluated in an operant paradigm consisting of acquisition and maintenance; extinction; deprivation and relapse; conflict. D2-receptor agonists, quinpirole (0.03 mg/Kg, i.p.) and ropinirole (0.03 mg/Kg, i.p.), and CB1-receptor antagonist, AM281 (1 mg/Kg, i.p.), were administered during different phases of the experiment. Our results show that oral ACD readily induced the acquisition and maintenance of an operant drinking-behaviour, even during reinstatement and conflict. Quinpirole decreased lever presses for ACD during extinction (p<0.05) and relapse (p<0.01; p<0.001) Ropinirole, administered during abstinence, reduced ACD intake during reinstatement (p<0.001). AM281 significantly decreased lever presses for ACD during extinction (p<0.001), relapse (p<0.001) and conflict (p