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

Abstract

Brain cannabinoid CB1 receptors are expressed in neural areas that contribute to movement such as basal ganglia, where they co-localize with dopamine D1 and D2 receptors. The objective of the present study was to further study the functional role of CB1 receptors along with D1 and D2 dopamine receptors of basal ganglia by local injections of SR141716A (CB1 receptor antagonist), SKF-38393 (D1 agonist), and quinpirole (D2 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 D1 or D2 dopamine receptor agonists alone reduced turning in parkinsonian rats. At the pallidal and subthalamic levels, D1 (not D2) 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 D1 and D2 dopamine receptor function. At the pallidal and subthalamic nucleus levels, motor effects after SR14716A are not associated to modulation of D1 and D2 receptor function.

Keywords

• CB1 antagonism
• SR141716A
• Striatum
• Globus pallidus
• Subthalamic nucleus
• D1 receptor