6-cyano-7-nitroquinoxaline-2-3-dione and 2-4-methanoglutamate

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 behavior. The stimulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid or N-methyl-D-aspartate glutamate receptors in the nucleus accumbens with either alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid or 1-aminocyclobutane-cis-1,3-dicarboxylic acid, respectively, decreased the number of cocaine-reinforced responses, suggesting an enhancement in the rewarding properties of cocaine. In contrast, blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptors with N-methyl-D-aspartate, or N-methyl-D-aspartate receptors with dizocilpine maleate or 2-amino-5-phosphonovaleric 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 treatment in the nucleus accumbens reinstated cocaine-seeking behavior. However, alpha-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-drug-paired levers. These results suggest that stimulation of glutamate receptors in the nucleus accumbens augments the reinforcing effect of cocaine, yet glutamate transmission is not required to maintain cocaine self-administration. In addition, increased glutamate transmission in the nucleus accumbens may be involved in facilitating the relapse to cocaine-seeking behavior.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Anesthetics, Local; Animals; Behavior, Addictive; Behavior, Animal; Benzazepines; Cocaine; Cocaine-Related Disorders; Dizocilpine Maleate; Dopamine Antagonists; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Feeding Behavior; Glutamates; Glutamic Acid; Male; Nucleus Accumbens; Procaine; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Recurrence; Self Administration; Synaptic Transmission