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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
Author(s) -
Minabe Yoshio,
Ashby Charles R.
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199702)25:2<196::aid-syn10>3.0.co;2-x
Subject(s) - ventral tegmental area , pars compacta , substantia nigra , dopamine , apomorphine , endocrinology , chemistry , medicine , pharmacology , antagonist , dopaminergic , biology , receptor
In this study, we examined the effect of the acute and chronic administration of the selective neurokinin 2 (NK 2 ) receptor antagonist SR 48968 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 μg/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 administration of 1 mg/kg, i.p., of SR 48968, but not its inactive enantiomer SR 48965, produced a significant increase in the number of spontaneously 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 controls. The pretreatment of animals with 1 mg/kg, i.p., of SR 48968 significantly potentiated the suppressant action of (+)‐apomorphine on spontaneously active SNC and VTA DA cells. In contrast to its acute effects, the administration of 1 mg/kg, i.p., of SR 48968 once daily for 21 days produced a significant decrease in the number of spontaneously active DA cells in the SNC and VTA. The decrease in the number of spontaneously active VTA DA cells was not reversed by (+)‐apomorphine administration; 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 depolarization block. Overall, these results suggest that the acute and chronic administration of SR 48968 alters the number of spontaneously active midbrain DA neurons in anesthetized rats. Synapse 25:196–204, 1997. © 1997 Wiley‐Liss, Inc.