Functional signature of cocaine addiction in the nucleus accumbens of adult rats

FERNANDO KASANETZ; ROBERT N, LAFOURCADE M, PIAZZA PV, DEROCHE-GAMONET V ; OLIVIER J MANZONI

Bordeaux

Congreso; 9e Colloque de la Societé Française des Neurosciences; 2009

Societé Française des Neurosciences

Addiction is defined as a compulsive drug taking despite severe negativeconsequences for the users. Recently, we introduced a new rat model thatclosely mimics the behavior normally observed in a small proportion of humandrug users. Accordingly, after a prolonged experience of cocaine selfadministration (~80 consecutive days) only 15-20% of the rats displayed thebehavioral hallmarks of addiction. This unique model allows for the first timestudying the neurobiological basis of vulnerability to drug abuse and therebysearches for new molecular targets for therapeutic intervention in drugaddiction.Here, by using and ex-vivo approach, we report the synaptic and cellularcorrelates of cocaine addiction in the nucleus accumbens (NAc). Whole cellpatch 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 inaddicts: the number of action potentials elicited by escalating depolarizingcurrent steps was reduced (Two Way ANOVA, p<0.05). Overall, this resultsuggests a lack of cellular and synaptic adaptations in addicts. Activity-dependent synaptic plasticity is thought to underlie learningand memory and to be the loci of pathological maladaptations. We tested howaddiction to cocaine impacted on synaptic plasticity in the NAc. We found thatNMDA receptor-mediated long-term depression induced with a pairing protocol wasabsent in the NAc of ?addict? rats (EPSC % of baseline: sham: 66 ± 7, ?user?:77 ± 6, ?addict?: 119 ± 17; One Way ANOVA p<0.01). This is the firstdemonstration of a specific correlation between addictive behaviour and alteredsynaptic plasticity. Altogether, our data suggest that cocaine addiction is characterized bya lack of cellular adaptations and a specific abolition of synaptic plasticityin the cortico-mesolimbic pathway.