The effects of acute or repeated cocaine administration on nerve terminal glutamate within the rat mesolimbic system

Cocaine administration alters glutamate function within several brain regio ns. Using quantitative electron microscopic immunocytochemistry, the presen t study investigted the effect of repeated intermittent cocaine (resulting in in behavioral sensitization) or acute cocaine administration on the dens ity of glutamate immunogold labeling within nerve terminals. Rats were trea ted daily with saline or cocaine for 7 days. Following a 14-day withdrawal animals were challenged with saline or cocaine. On the challenge day, most (75%) animals that received cocaine repeatedly showed a heightened locomoto r response to cocaine compared to the first day of cocaine administration, and were considered behaviorally sensitized. Three days after the challenge, glutamate immunogold labeling was quantifie d in nerve terminals making asymmetrical synaptic contacts within the core and shell of the nucleus accumbens, ventral tegmental area and medial prefr ontal cortex. There was a decrease in such labeling in the nucleus accumben s in the group receiving acute cocaine. Locomotor activity was positively c orrelated with glutamate immunolabeling within nerve terminals in the nucle us accumbens core only for the cocaine-sensitized group. Nerve terminal glu tamate immunolabeling in the nucleus accumbens. core, but not the shell, wa s increased in the non-sensitized compared to the cocaine-sensitized group. In the ventral tegmental area, glutamate immunolabeling was significantly higher in the cocaine-sensitized compared to the acute cocaine group. In th e prefrontal cortex, there were no significant differences in glutamate imm unogold labeling between treatment groups. This study indicates that acute cocaine administration significantly decrea ses nerve terminal glutamate immunoreactivity in the nucleus accumbens. We suggest that sensitization results in differential changes in the nucleus a ccumbens core versus the shell, and may alter presynaptic mechanisms regula ting glutamate release or re-uptake in the core. (C) 2001 IBRO. Published b y Elsevier Science Ltd. All rights reserved.