EFFECT OF THE ACUTE AND CHRONIC ADMINISTRATION OF THE SELECTIVE NEUROKININ(2) RECEPTOR ANTAGONIST SR-48968 ON MIDBRAIN DOPAMINE NEURONS IN THE RAT - AN IN-VIVO EXTRACELLULAR SINGLE-CELL STUDY

In this study, we examined the effect of the acute and chronic adminis tration of the selective neurokinin(2) (NK2) receptor antagonist SR 48 968 on the activity of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized, male rats. This was accomplished using the technique of in vivo, extracellular single cell recording. The intravenous (i.v .) administration of SR 48968 (10-1280 mu g/kg) did not significantly alter the basal firing rate or pattern of either spontaneously active SNC or VTA DA neurons compared to control. However, the acute administ ration of 1 mg/kg, i.p., of SR 48968, but not its inactive enantiomer SR 48965, produced a significant increase in the number of spontaneous ly active DA cells in the SNC (48%) and VTA (28%) compared to vehicle controls. The i.p. administration of SR 48968 did not alter the basal firing pattern of either SNC or VTA DA neurons compared to vehicle con trols. The pretreatment of animals with 1 mg/kg, i.p., of SR 48968 sig nificantly potentiated the suppressant action of (+)-apomorphine on sp ontaneously active SNC and VTA DA cells. In contrast to its acute effe cts, the administration of 1 mg/kg, i.p., of SR 48968 once daily for 2 1 days produced a significant decrease in the number of spontaneously active DA cells in the SNC and VTA. The decrease in the number of spon taneously active VTA DA cells was not reversed by (+)-apomorphine admi nistration; in fact, a further decrease in the number of VTA DA cells was observed. This suggests that the SR 48968-induced decrease in the number of spontaneously active DA neurons may not be the result of dep olarization block. Overall, these results suggest that the acute and c hronic administration of SR 48968 alters the number of spontaneously a ctive midbrain DA neurons in anesthetized rats. (C) 1997 Wiley-Liss, I nc.