Nigrostriatal dopamine actions on the D2 receptors mediate methamphetamine effects on the striatonigral substance P system.

Abstract:

:Multiple administrations of methamphetamine to rats produced elevated concentrations of substance P-like immunoreactivity within the substantia nigra, an effect which is believed to be mediated by increases in dopaminergic activity induced by methamphetamine. The results reported here demonstrate that the effect of methamphetamine is mediated specifically by the dopamine pathway in the nigrostriatum. Thus, extensive destruction of dopamine neurons in the nigrostriatum by lesions induced by 6-hydroxydopamine or blockade of synthesis of dopamine with alpha-methyl-p-tyrosine prevented the increases in substance P-like immunoreactivity in the nigra, induced by methamphetamine. Similarly, the concurrent administration of the D2 receptor antagonist, sulpiride, also prevented the effects of methamphetamine on substance P-like immunoreactivity in a dose-dependent way. In addition, multiple administrations of the D2 agonist, RU24926, elevated, whereas the DI agonist, SKF38393, decreased the content of substance P-like immunoreactivity in the nigra. The effects of methamphetamine were not altered in rats with lesions induced by 5,7-dihydroxytryptamine. Thus, these findings suggest that the effect of methamphetamine on the striatonigral substance P pathway is mediated by nigrostriatal dopaminergic actions on D2 receptors.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Sonsalla PK,Gibb JW,Hanson GR

doi

10.1016/0028-3908(86)90139-5

subject

Has Abstract

pub_date

1986-11-01 00:00:00

pages

1221-30

issue

11

eissn

0028-3908

issn

1873-7064

journal_volume

25

pub_type

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