Cocaine increases extraneuronal levels of aspartate and glutamate in the nucleus accumbens

Intracerebral microdialysis was used to assess the effects of cocaine-HCl on extracellular concentrations of the excitatory amino acids aspartate and glutamate in the nucleus accumbens of awake, freely moving rats. After an initial equilibration period, cocaine (7.5, 15 or 30 mg/kg) or saline was injected i.p., and samples were collected for an additional 2 h. The highest dose of cocaine (30 mg/kg, i.p.) caused a 4-fold increase in glutamate levels and an 18-fold increase in aspartate levels over baseline. To verify that the source of the extracellular aspartate and glutamate was neuronal, additional experiments were conducted using Ca2+-free microdialysis buffer, and buffer containing 10 mu M tetrodotoxin. Local perfusion with Ca2+-free buffer reduced the increase of extracellular aspartate and glutamate in rats injected with 30 mg/kg cocaine. Tetrodotoxin significantly decreased the cocaine-induced increase in excitatory amino acids, but not the behavioral response.