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  • Title: Blockade of tachykinin NK1 receptors by CP-96345 enhances dopamine release and the striatal dopamine effects of methamphetamine in rats.
    Author: Gygi SP, Gibb JW, Johnson M, Hanson GR.
    Journal: Eur J Pharmacol; 1993 Nov 30; 250(1):177-80. PubMed ID: 7509751.
    Abstract:
    The nonpeptide, tachykinin NK1 receptor antagonist, CP-96345, permits the study of the physiological role of extrapyramidal substance P systems. Using microdialysis, we observed that locally applied CP-96345 (200 nM) caused a significant increase in dopamine release in the striatum as well as substantially enhancing striatal dopamine release caused by a low dose of methamphetamine (0.5 mg/kg s.c.). In addition, multiple systemic administrations of CP-96345 almost doubled the dopamine-mediated responses of the striatal neurotensin and dynorphin systems to high doses of methamphetamine (10 mg/kg/dose s.c.). Our findings suggest that the physiological role of substance P released in the striatum is to decrease the activity of the nigrostriatal dopamine pathway.
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