Dopamine turnover and glutamate decarboxylase activity in the rat brain after acute and chronic treatment with raclopride, a dopamine D 2-selective antagonist

Abstract

The effect of acute and chronic (94, 141 and/or 199 days) oral treatment of rats with the dopamine D 2-selective antagonist raclopride (0, 5,15,45 and 135 μmol/kg) upon the turnover of dopamine in the striatum and limbic system and upon the activity of glutamate decarboxylase (GAD) in the s. nigra, striatum and frontal cortex has been investigated. A dose-dependent tolerance to the effect of raclopride on the turnover of dopamine was observed after chronic treatment, although the degree of tolerance was marginal at the 5 and 15 μmol/kg doses. Acute treatment with raclopride was without effect on the activity of GAD in the s. nigra, striatum or frontal cortex, whereas chronic (199 days) treatment with 45 μmol/kg of raclopride produced an increase in the activity of GAD in the s. nigra and striatum.