Synaptic and cellular correlates of cocaine addiction in the nucleus accumbens of adult rats

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

Ginebra

Congreso; 6th Fens Forum of Neuroscience; 2008

FENS

Addiction is amajor pathology 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, 15-20% of the rats displayed the behavioral hallmarksof addiction. This unique model allows studying the neurobiological basis ofvulnerability to drug abuse. Here, we investigated the synaptic and cellularcorrelates of cocaine addiction in the synapses of the mesocorticolimbic systemof adult rats. Whole cell patch clamp was performed in the brain slicepreparation in the core of the nucleus accumbens. Current clamp recordingsrevealed how cocaine altered the intrinsic properties and the excitability ofmedium spiny neurons. Cocaine addiction was not correlated to significantchanges in the evoked or spontaneous activities of both GABAergic andglutamatergic synapses impinging on medium spiny neurons. A significantmodification of the ratio of AMPA to NMDA receptors mediated-currents andremarkable alterations in the expression of NMDA receptors-dependent long-termpotentiation were discovered in response to cocaine. In contrast, cocaineaddiction had no effect on a presynaptic form of long-term depression mediatedby presynaptic metabotropic glutamate receptors. Finally, tri-dimensionalconfocal reconstruction unveiled the real effects of cocaine on the dendriticarborization of medium spiny neurons. Our study reveal for the first time thestructural and synaptic correlates of cocaine addiction in the nucleusaccumbens.