EFFECTS OF A CANNABINOID ON SPONTANEOUS AND EVOKED NEURONAL-ACTIVITY IN THE SUBSTANTIA-NIGRA PARS RETICULATA

Single unit electrophysiology was used to explore the role of cannabin oid receptors in the substantia nigra pars reticulata. Intravenous and intraperitoneal injections of the potent and selective synthetic cann abinoid dihydro-5-methyl-3-[(4-morphorinyl)methyl]pyrrolo[ 1,2,3-de]-1 ,4-benzoxazin-6-yl](1-naphthalenyl) methanone (WIN 55,212-2) produced modest but significant increases in the spontaneous firing rate of neu rons in the substantia nigra pars reticulata. In a second set of exper iments, WIN 55,212-2 (up to 1.0 mg/kg i.v.) antagonized the inhibition of firing produced in the substantia nigra pars reticulata by electri cal stimulation of the striatum. The pharmacological specificity of th is effect was demonstrated using the inactive enantiomer WIN 55,212-3. The possibility that WIN 55,212-2 exerts its effects by regulating ga mma-aminobutyric acid (GABA) release from striatonigral fibers was sug gested by the observation that bicuculline (up to 0.5 mg/kg i.v.) reve rsed the effect of striatal stimulation. It thus appears that cannabin oid receptors on striatonigral neuron terminals may regulate movement by disinhibiting the activity of substantia nigra pars reticulata neur ons, perhaps by inhibiting the release of GABA into the substantia nig ra pars reticulata.