The endogenous cannabinoid system works as a feedback signal controlling dopamine-induced facilitation of motor behaviors. The present study explored whether a single acute stimulation of CB1 cannabinoid receptors with (-)-Delta9-tetrahydrocannabinol (THC, 5 mg kg(-1) i.p.) results in modifications in the sensitivity to the acute behavioral effects of the dopamine D2/D3 receptor agonist quinpirole (0.025, 0.25 and 1 mg kg(-1), s.c.) 24 h after THC administration. Cannabinoid pretreatment increased the sensitivity to quinpirole-induced hyperlocomotion 24 h after its administration. The data indicated that THC induced a desensitization of cannabinoid receptors, as revealed by a reduction in CB1 receptor-agonist induced GTP-gamma-S incorporation in striatal membranes. These results might be relevant for understanding the effect of cannabinoid exposure in dopamine-related neuropsychiatric disorders.
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