INCREASE IN MESO-PREFRONTAL DOPAMINERGIC ACTIVITY AFTER STIMULATION OF CB1 RECEPTORS BY CANNABINOIDS

The intravenous administration of the psychoactive constituent of mari juana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) (62.5-1000 mu g/kg ), and the synthetic cannabinoid agonist WIN 55212,2 (WIN) (62.5-500 m u g/kg), produced a dose-related increase in the firing rate and burst firing in the majority of antidromically identified meso-prefrontal d opaminergic neurons. In a restricted number of neurons (n = 4), WIN ad ministration did not increase firing rate but produced an increment of bursting activity. These effects of the cannabinoids were reversed by the intravenous administration of SR 141716 A, a selective cannabinoi d antagonist (1 mg/kg), per se ineffective to modify the electrical ac tivity of dopaminergic neurons. The results indicate that stimulation of cannabinoid CB1 receptors produces an activation of meso-prefrontal dopaminergic transmission. Considering that supranormal stimulation o f D1 dopamine receptors in the prefrontal cortex has been shown to imp air working memory, the present results suggest that the negative effe cts of cannabinoids on cognitive processes might be related to the act ivation of dopaminergic transmission in the prefrontal cortex.