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Blockade of Tachykinin NK1 Receptors by CP-96345 Enhances Dopamine Release and the Striatal Dopamine Effects of Methamphetamine in Rats

Blockade of Tachykinin NK1 Receptors by CP-96345 Enhances Dopamine Release and the Striatal Dopamine Effects of Methamphetamine in Rats

S P Gygi, J W Gibb, M Johnson, G R Hanson

Eur J Pharmacol. 1993 Nov 30;250(1):177-80.

PMID: 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP132746602	CP-96345		132746-60-2	Price

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