A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior

This study investigated the effect of ionotropic glutamate receptor agonist or antagonist administration into the nucleus accumbens on the maintenance of cocaine self-administration and the reinstatement of cocaine-seeking be havior. The stimulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propri onic acid or N-methyl-D-aspartate glutamate receptors in the nucleus accumb ens with either alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid o r 1-aminocyclobutane-cis-1,3-dicarboxylic acid, respectively, decreased the number of cocaine-reinforced responses, suggesting an enhancement in the r ewarding properties of cocaine. In contrast, blockade of alpha-amino-3-hydr oxy-5-methylisoxazole-4-proprionic acid receptors with N-methyl-D-aspartate , or N-methyl-D-aspartate receptors with dizocilpine maleate or 2-amino-5-p hosphonovaleric acid had no selective effect on the maintenance of cocaine self-administration. Following one week of extinction from the reinforcing cue of the drug-paired lever, both alpha-amino-3-hydroxy-5-methylisoxazole- 4-proprionic acid and 1-aminocyclobutane-cis-1,3-dicarboxylic acid treatmen t in the nucleus accumbens reinstated cocaine-seeking behavior. However, al pha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid treatment increased responding only on the drug-paired lever, while 1-aminocyclobutane-cis-1,3 -dicarboxylic acid increased responding on both the drug-paired and non-dru g-paired levers. These results suggest that stimulation of glutamate receptors in the nucleu s accumbens augments the reinforcing effect of cocaine, yet glutamate trans mission is not required to maintain cocaine self-administration. In additio n, increased glutamate transmission in the nucleus accumbens may be involve d in facilitating the relapse to cocaine-seeking behavior. (C) 1999 IBRO. P ublished by Elsevier Science Ltd.