Effects on turning of microinjections into basal ganglia of D1 and D2 dopamine receptors agonists and the cannabinoid CB1 antagonist SR141716A in a rat Parkinson's model

Brain cannabinoid CB1 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 CB1 receptors along with D-1 and D-2 dopamine receptors of basal ganglia by local injections of SR141716A (CB1 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, CB1 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. (C) 2004 Elsevier Inc. All rights reserved.