© Neuroscience-Net Volume 1, Article #10008

Received July 6, 1996 Accepted for Publication September 18, 1996 Published October 2, 1996

A previous study demonstrated that the development of behavioral sensitization to repeated cocaine was associated with an increase in glutamate transmission in the nucleus accumbens three weeks after discontinuing the daily injection regimen. The present study extends these findings by examining changes in glutamate transmission in the nucleus accumbens between 1 and 3 days after discontinuing repeated daily cocaine or saline treatment. In all experiments, rats were pretreated with cocaine (15 mg/kg, ip X 2 days, 30 mg/kg, ip X 5 days) or saline. The intra-accumbens administration of AMPA (0.1 µg) produced a motor response that was significantly greater in cocaine- than in saline-pretreated rats. The augmented behavioral response to AMPA occurred only in rats that developed behavioral sensitization to repeated cocaine, and not in the subpopulation of rats pretreated with daily cocaine that did not develop behavioral sensitization. Using microdialysis, it was shown that the augmented behavioral response to AMPA was not the result of enhanced dopamine transmission since the administration of AMPA (0.1-100.0 µM) through a microdialysis probe in the nucleus accumbens produced an equivalent increase in extracellular dopamine in both the saline and cocaine treatment groups. In vivo microdialysis also was used to measure extracellular glutamate in the nucleus accumbens and it was shown that a cocaine injection (15 mg/kg, ip) did not significantly alter extracellular glutamate levels in either the repeated cocaine or saline groups. These results indicate that, compared to what was observed three weeks after discontinuing daily cocaine, at early withdrawal there are relatively smaller alterations in glutamate transmission in the nucleus accumbens that are associated with the development of behavioral sensitization.