CHRONIC COCAINE ADMINISTRATION INCREASES TYROSINE-HYDROXYLASE ACTIVITY IN THE VENTRAL TEGMENTAL AREA THROUGH GLUTAMINERGIC-RECEPTOR AND DOPAMINERGIC D-2-RECEPTOR MECHANISMS

Tyrosine hydroxylase activity was measured in the brain of rats treate d chronically with saline or cocaine (10 mg/kg, 2 x day, for 7 days). Tyrosine hydroxylase activity was significantly increased in the ventr al tegmental area 1, 6 and 12 weeks after the last treatment with coca ine. The increase in tyrosine hydroxylase activity at 6 weeks after th e last cocaine injection was prevented by the prior administration of MK-801, haloperidol or clozapine but not by the D-1 receptor antagonis t, SCH-23390. SCH-23390 produced a significant increase in tyrosine hy droxylase activity when administered with saline. These data indicate that glutaminergic and dopaminergic D-2-receptor mediated mechanisms a re important in regulating the effect of cocaine on the ventral tegmen tal area.