Alterations in nerve terminal glutamate immunoreactivity in the nucleus accumbens and ventral tegmental area following single and repeated doses of cocaine

Rationale and objectives: Previous studies have demonstrated that sensitization to repeated doses of cocaine results in prolonged changes in glutamate transmission. However, little is known about long-term changes in glutamate transmission following a single dose of cocaine. Our laboratory has previously reported that a single dose of cocaine, but not repeated cocaine, decreased the density of presynaptic nerve terminal glutamate immunolabeling in the nucleus accumbens when measured 3 days later. This study extends the results of our previous work by examining nerve terminal glutamate immunoreactivity 17 days after the last dose of cocaine. Methods: Quantitative electron-microscopic immunocytochemistry was used to determine the density of presynaptic nerve terminal glutamate immunoreactivity in rats that received single or repeated doses of cocaine followed by 17 days of withdrawal. Animals that received repeated cocaine were separated into behaviorally sensitized and non-sensitized groups based on individual differences between cocaine-stimulated locomotor activity on the first and last days of cocaine administration. Results: There were significant decreases in the density of presynaptic nerve terminal glutamate immunoreactivity in the nucleus accumbens core of the group that received a single dose of cocaine. The repeat cocaine groups had significant decreases in nerve terminal glutamate immunolabeling in the ventral tegmental area. Conclusions: Acute cocaine administration resulted in a significant loss of nerve terminal glutamate immunoreactivity that was persistent in the nucleus accumbens core but there were only transient changes in the shell. Nerve terminal glutamate immunoreactivities in the behaviorally sensitized and non-sensitized groups were not significantly different from one another, which suggests that cocaine-induced alterations in presynaptic glutamate immunoreactivity may not be sufficient for the expression, of behavioral sensitization.