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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
Author(s) -
Minabe Yoshio,
Emori Kenji,
Toor Alon,
Stutzmann Grace E.,
Ashby Charles R.
Publication year - 1996
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(199601)22:1<35::aid-syn4>3.0.co;2-j
Subject(s) - ventral tegmental area , dopamine , pars compacta , apomorphine , chemistry , substantia nigra , antagonist , pharmacology , midbrain , medicine , endocrinology , systemic administration , extracellular , dopaminergic , receptor , in vivo , central nervous system , biology , biochemistry , microbiology and biotechnology
In this study, we examined the effect of acute and chronic administration of the selective neurokinin 1 receptor antagonist CP 96,345 on the basal activity of spontaneously active dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA). This was accomplished using the technique of in vivo, extracellular single unit recording in anesthetized rats. The intravenous (i.v.) administration of CP 96,345 (0.01–1.28 mg/kg) did not significantly alter 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 96,345 produced a significant decrease in the number of spontaneously active SNC and VTA dopamine cells compared to vehicle‐treated rats. In contrast 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 significantly 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 potentiated the suppressant action of (+)‐apomorphine on the basal firing rate of spontaneously active SNC and VTA DA cells. The chronic administration 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 by the systemic administration of (+)‐apomorphine (50 μg/kg, i.v.), suggesting that the reduction in the number of spontaneously active DA cells produced by CP 96,345 is probably not the result of depolarization inactivation. Overall, our results indicate that the tonic activation of NK 1 receptors by substance P may be necessary to maintain the spontaneous activity of a proportion of midbrain DA neurons. © 1996 Wiley‐Liss, Inc.