Effects on turning of microinjections into basal ganglia of D(1) and D(2) dopamine receptors agonists and the cannabinoid CB(1) antagonist SR141716A in a rat Parkinson's model.

Brain cannabinoid CB(1) receptors are expressed in neural areas that contribute to movement such as basal ganglia, where they co-localize with dopamine D(1) and D(2) receptors. The objective of the present study was to further study the functional role of CB(1) receptors along with D(1) and D(2) dopamine receptors of basal ganglia by local injections of SR141716A (CB(1) receptor antagonist), SKF-38393 (D(1) agonist), and quinpirole (D(2) agonist), in a rat Parkinson's model. Turning response after amphetamine was considered as the parkinsonian variable for quantifying motor effects of drugs. The findings indicated that, after intrastriatal infusions, both D(1) or D(2) dopamine receptor agonists alone reduced turning in parkinsonian rats. At the pallidal and subthalamic levels, D(1) (not D(2)) receptor stimulation also reduced rotation. Regarding SR141716A-induced effects, CB(1) antagonism reduced motor asymmetry in parkinsonian rats after injections into striatum, globus pallidus, and to a lesser extent, subthalamic nucleus. At the level of dorsal striatum, effects of SR141716A were mediated through an opposite modulation of D(1) and D(2) dopamine receptor function. At the pallidal and subthalamic nucleus levels, motor effects after SR14716A are not associated to modulation of D(1) and D(2) receptor function.