Synaptic and cellular correlates of cocaine addiction in rats

FERNANDO KASANETZ; VÉRONIQUE DEROCHE-GAMONET, NADÈGE BERSON, ERIC BALADO, MATHIEU LAFOURCADE, OLIVIER MANZONI, PIER VINCENZO PIAZZA

Nice

Workshop; European College of Neuropsychopharmacology (ECNP) Workshop on Neuropsychopharmacology for Young Scientists; 2009

European College of Neuropsychopharmacology

Addiction is defined as a compulsive drug taking despite severe negative consequences for the users. Recently, we introduced a new rat model that closely mimics the behavior normally observed in a small proportion of human drug users (1). Accordingly, after a prolonged experience of cocaine self administration (~80 consecutive days) only 15-20% of the rats displayed the behavioral hallmarks of addiction. This unique model allows for the first time studying the neurobiological basis of vulnerability to drug abuse and thereby searches for new molecular targets for therapeutic intervention in drug addiction. Here, by using and ex-vivo approach, we report the synaptic and cellular correlates of cocaine addiction in the nucleus accumbens (NAc) a central structure of the cortico-mesolimbic reward pathway. Whole cell patch clamp recordings were performed in brain slices prepared from adult rats. Three groups of animals were analyzed: sham, non-addict cocaine users (?user?) and addict cocaine users (?addict?).Neuronal excitability was reduced in the NAc of users but was normal in addicts: the number of action potentials elicited by escalating depolarizing current steps was reduced (Two Way ANOVA, p