Repeated cocaine treatment alters tyrosine hydroxylase in the rat nucleus accumbens.

To determine whether repeated exposure of cocaine affects the dopaminergic innervation of the nucleus accumbens, we employed a typical cocaine-dosing regimen in adult male Sprague-Dawley rats followed by an immunocytochemical analysis of tyrosine hydroxylase (TH). Treatment consisted of bi-daily injections of saline or 15 mg/kg cocaine for 5 consecutive days. After 2 or 14 days of withdrawal, sections of the nucleus accumbens (NAc) were processed for tyrosine hydroxylase and the number of immunoreactive varicosities in the core and shell were quantified. Two days after treatment, the core demonstrated a decrease, while after 14 days of treatment, the shell was found to contain significantly more TH immunoreactive varicosities. Additionally, 2 days post-cocaine treatment, core-shell differences were found, however moderate differences were also found in the saline treatment group, making the absolute effects of cocaine difficult to separate from injection and handling effects at this time point. These results suggest that the shell of the NAc may undergo alterations that could be involved with behavioral sensitization that typically results from such cocaine treatment regimens.

An examination of glutamate decarboxylase(65) immunoreactive puncta with respect to rat ventral pallidum neurons after repeated cocaine administration.

The ventral pallidum is known to have topographically organized reciprocal gamma-aminobutyric acid-ergic projections with the nucleus accumbens, and changes in these connections may play a role in mediating the behavioral sensitizing effect of repeated exposure to cocaine. The present study investigated glutamate decarboxylase-65 (GAD(65)) immunoreactivity in the rat ventral pallidum after repeated cocaine administration. Male Sprague-Dawley rats were administered bi-daily injections of 15 mg/kg cocaine or saline vehicle for 5 consecutive days. After 2 or 14 days of withdrawal, ventral pallidal sections were immunocytochemically processed for GAD(65) immunoreactive puncta and counts were made. In both groups, there were no statistically significant differences in the number or density of GAD(65) puncta in medial or lateral portions either in contact with neuronal cell bodies or in the neuropil after 2 or 14 days of withdrawal. The results suggest that there is no alteration in the number of GABAergic boutons expressing GAD(65) immunoreactivity in the ventral pallidum after repeated exposure to cocaine.