Chronic L-dopa treatment of rats and mice does not change the sensitivity of post-synaptic dopamine receptors.

The effects of L-Dopa + benserazide (L-Dopa + B) treatment on pre- and postsynaptic dopamine (DA) receptors were studied. Mice treated once daily P.O. with L-Dopa (200 mg/kg) + B (50 mg/kg) or vehicle for 10 days were used on the 11th day. After premedication with reserpine and alpha-methyltyrosine (alpha-MT), apomorphine (0.5-2.0 mg/kg) produced locomotor stimulation which was of equal intensity in the 3 treatment groups, even when the treatment dose of L-Dopa was increased to 400 mg/kg per day. In contrast, low doses of apomorphine (0.1-0.5 mg/kg) produced locomotor depression in B- and vehicle-treated mice but not in L-Dopa + B-treated mice. In rats treated I.P. twice daily with L-Dopa (200 mg/kg) + B (50 mg/kg), B (50 mg/kg) or vehicle for 12 days, apomorphine produced an equivalent degree of stereotypy on the 13th day in each of the 3 treatment groups. There were no treatment group differences in the binding of [3H]-spiperone or [3H]-leu-enkephalin to rat striatal membranes. The data suggest that long-term L-Dopa + B treatment of mice and rats does not change the sensitivity of postsynaptic DA receptors but may affect the sensitivity of DA autoreceptors.