Behavioural and biochemical alterations in the function of dopamine receptors following repeated administration of l-DOPA to rats

Abstract

Rats received l-DOPA (40 or 200 mg/kg, i.p.) for 14 days, followed by a 3 day withdrawal period. Spontaneous locomotor activity was not altered by repeated administration of l-DOPA. Rats treated with l-DOPA (200 mg/kg) showed identical locomotor hypoactivity in response to small doses of apomorphine when compared to saline-treated control animals. However, hyperactivity induced by large doses of apomorphine was reduced by prior treatment with l-DOPA (200 mg/kg). The smaller dose of l-DOPA (40 mg/kg) did not alter the locomotion induced by apomorphine. Stereotyped behaviour induced by apomorphine was enhanced by prior treatment with both 40 and 200 mg/kg of l-DOPA. The treatment regimes with l-DOPA had no effect on the concentrations of apomorphine in the striatum. Administration of l-DOPA (40 or 200 mg/kg) followed by withdrawal for 3 days, had no effect on the concentrations of dopamine, homovanillic acid (HVA) or 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. The B max and K D for the binding of [ 3H]spiperone. [ 3 H]N,n- propylnorapomorphme (NPA) and [ 3H]piflutixol in the striatum was not altered by drug treatment. Similarly, the formation of dopaminestimulated cyclic AMP in homogenates of striatum was unaltered by repeated administration of l-DOPA. Repeated administration of l-DOPA for 14 days in the rat appears to result in altered behaviour mediated by dopamine in the absence of any apparent change in the function of dopamine receptors in the striatum.