Differential treatment regimen-related effects of HU210 on CB(1) and D(2)-like receptor functionality in the rat basal ganglia.

Functional linkages between the cannabinoid CB(1) and the dopaminergic systems have been reported although the observations and the mechanisms hypothesizing their interactions at the G protein-coupled receptor (GPCR) functionality level are conflicting. Administration of a potent cannabinoid agonist, HU210, at various doses (25-100 μg/kg) and treatment regimens (1- to 14-day treatment) in rats was carried out to investigate the effect of HU210 treatment on the CB(1) and D(2)-like agonist-mediated GPCR activation. The desensitizations (reduced coupling) of both D(2) agonist- and CB(1) agonist-mediated GPCR activation was found to be treatment duration dependent and region specific, suggesting implication of receptor tolerance and adaptation due to the cannabinoid treatment. The effect of HU210 on the CB(1) agonist-mediated GPCR desensitization in all treatment groups was not dose dependent. The desensitization of D(2)-like receptors found after a cannabinoid treatment in this study strengthens the evidence that the two neurotransmitter systems interact at the intercellular level; this interaction might occur via multiple mechanisms, which also vary according to region.