Acetaldehyde (ACD), the first metabolite of ethanol, directly enhances dopamine neurotransmission (1) and has rewarding and motivationalproperties 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, thepresent study aimed at investigating the effects of a direct manipulation of the DAergic synapse, and the contribution of the endocannabinoid system onoral 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-receptorantagonist, 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, evenduring 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 duringextinction (p<0.001), relapse (p<0.001) and conflict (p<0.001). These data suggest that whereas the direct modulation of the dopaminergic synapseinfluences drug-seeking and relapse behaviour, the endocannabinoid system may also play a role in shock-paired compulsive ACD intake. These findings highlight the mandatory need for further investigation on the therapeutical potential played by the endocannabinoid system taking into account its crucial role in alcohol, and ACD neuropharmacology.
|Numero di pagine||51|
|Stato di pubblicazione||Published - 2014|