Acute and chronic administration of the selective sigma(1) receptor agonist SA4503 significantly alters the activity of midbrain dopamine neurons in rats: An in vivo electrophysiological study

In this study, we examined the effect of the acute and repeated administrat ion of the selective sigma (sigma)(1) receptor agonist 1-(3,4-dimethoxyphen ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) on the number and firing pattern of spontaneously active dopamine (DA) neurons in substan tia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anestheti zed, male Sprague-Dawley rats. This was accomplished using the technique of in vivo extracellular single unit recording. The intravenous administratio n of SA4503 (0.01-1.28 mg/kg) did not significantly alter the firing rate o r pattern of spontaneously active DA neurons in either the SNC or VTA. A si ngle injection of either 0.1 or 0.3 mg/kg i.p, of SA4503 did not alter the number of spontaneously active SNC and VTA DA neurons. In contrast, a singl e injection of 1 mg/kg i.p. of SA4503 produced a significant decrease and i ncrease in the number of spontaneously active SNC and VTA DA neurons, respe ctively. Overall, the firing pattern parameters of spontaneously active SNC DA neurons were altered more significantly than those of spontaneously act ive VTA DA neurons following the acute administration of SA4503. The repeat ed administration (one injection per day for 21 days) of 0.3 and 1 mg/kg i. p. of SA4503 produced a significant increase in the number of spontaneously active VTA DA neurons. In addition, the repeated administration of SA4503 produced a greater alteration of the firing pattern of spontaneously active VTA compared to SNC DA neurons. Our results suggest that the administratio n of SA4503 significantly alters the activity of spontaneously active midbr ain DA neurons, particularly those in the VTA following repeated administra tion. (C) 1999 Wiley-Liss, Inc.