THE NMDA ANTAGONIST, DIZOCILPINE, ENHANCES COCAINE REINFORCEMENT WITHOUT INFLUENCING MESOACCUMBENS DOPAMINE TRANSMISSION

In order to assess the role of excitatory amino acids (EAAs) in the re inforcing property of cocaine, the NMDA antagonist, dizocilpine, or th e AMPA antagonist, DNQX; were administered to animals previously train ed to self-administer cocaine (1.0, 0.4 or 0.16 mg/kg per infusion). T he highest doses of dizocilpine (0.1 mg/kg, IF) and DNQX (30 mg/kg, IF ) significantly reduced operant responding for cocaine maintained on a fixed ratio schedule of reinforcement. However, whereas dizocilpine h ad no influence operant responding for food, DNQX significantly decrea sed level pressing for this reinforcer. These results indicate that an NMDA antagonist produces a relatively selective enhancement of cocain e reinforcement, while an AMPA antagonist decreases cocaine self-admin istration only at a close that also impairs responding for an alternat e reinforcer. A parallel in vivo microdialysis study pel formed in fre ely moving rats tested the effects of dizocilpine alone and in combina tion with cocaine on extracellular dopamine in the nucleus accumbens s hell. The results revealed that dizocilpine alone (0.01 mg/kg, IF) did not alter basal extracellular dopamine levels in the nucleus accumben s or spontaneous behavior. In addition, 0.1 mg/kg dizocilpine did not alter the increase ill dopamine in the accumbens shell of behavioral h yperactivity produced by cocaine (15 of 30 mg/kg), Collectively, these findings suggest that dizocilpine enhances the reinforcing effect of cocaine without influencing dopamine transmission in the nucleus accum bens shell.