Dopamine activation of endogenous cannabinoid signaling in dorsal striatum

We measured endogenous cannabinoid release in dorsal striatum of freely mov ing rats by microdialysis and gas chromatography/mass spectrometry. Neural activity stimulated the release of anandamide, but not of other endogenous cannabinoids such as 2-arachidonylglycerol. Moreover, anandamide release wa s increased eightfold over baseline after local administration of the D-2-l ike (D-2, D-3, D-4) dopamine receptor agonist quinpirole, a response that w as prevented by the D-2-like receptor antagonist raclopride. Administration of the D-1-like (D-1, D-5) receptor agonist SKF38393 had no such effect. T hese results suggest that functional interactions between endocannabinoid a nd dopaminergic systems may contribute to striatal signaling. In agreement with this hypothesis, pretreatment with the cannabinoid antagonist SR141716 A enhanced the stimulation of motor behavior elicited by systemic administr ation of quinpirole. The endocannabinoid system therefore may act as an inh ibitory feedback mechanism countering dopamine-induced facilitation of moto r activity.