THE EFFECT OF THE ACUTE AND CHRONIC ADMINISTRATION OF CP-96,345, A SELECTIVE NEUROKININ(1), RECEPTOR ANTAGONIST, ON MIDBRAIN DOPAMINE NEURONS IN THE RAT - A SINGLE-UNIT, EXTRACELLULAR RECORDING STUDY

In this study, we examined the effect of acute and chronic administrat ion of the selective neurokinin(1) receptor antagonist CP 96,345 on th e basal activity of spontaneously active dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and the ventral tegmental area (V TA). This was accomplished using the technique of in vivo, extracellul ar single unit recording in anesthetized rats. The intravenous (i.v.) administration of CP 96,345 (0.01-1.28 mg/kg) did not significantly al ter the firing rate of spontaneously active DA neurons in the SNC and VTA areas. The acute administration of 5 or 10 mg/kg, i.p., of CP 96,3 45 produced a significant decrease in the number of spontaneously acti ve SNC and VTA dopamine cells compared to vehicle-treated rats. In con trast to its effect on the number of spontaneously active DA neurons, the administration of 5 mg/kg, i.p., of CP 96,345 did not significantl y alter the basal firing pattern of either SNC or VTA DA neurons. The acute administration of CP 96,345 (10 mg/kg, i.p.) significantly poten tiated the suppressant action of (+)-apomorphine on the basal firing r ate of spontaneously active SNC and VTA DA cells. The chronic administ ration of CP 96,345 (5 or 10 mg/kg, i.p.) for 21 days also produced a significant decrease in the number of spontaneously active SNC and VTA DA cells compared to vehicle controls. This effect was not reversed b y the systemic administration of(+)-apomorphine (50 mu g/kg, i.v.), su ggesting that the reduction in the number of spontaneously active DA c ells produced by CP 96,345 is probably not the result of depolarizatio n inactivation. Overall, our results indicate that the tonic activatio n of NK1 receptors by substance P may be necessary to maintain the spo ntaneous activity of a proportion of midbrain DA neurons. (C) 1996 Wil ey-Liss, Inc.