N(G)-nitro-L-arginine methyl ester attenuates the maintenance and expression of methamphetamine-induced behavioral sensitization and enhancement of striatal dopamine release

H. Inoue, I. Arai, Shigenobu Shibata, S. Watanabe

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Abstract

We examined the roles of nitric oxide (NO) in methamphetamine (MAP)- induced behavioral sensitization and enhancement of striatal dopamine (DA) release using both in vive and in vitro methods. Repeated administration of MAP produced augmentation of MAP-induced locomotor activity after 3-day withdrawal of MAP and an enhancement of MAP-evoked DA release from striatal slices after 6-day withdrawal. When the NO synthase (NOS) inhibitor N(G)- nitro-L-arginine methyl ester (L-NAME) was administered only during the period of MAP withdrawal, the behavioral sensitization and enhancement of DA release were attenuated significantly. In contrast, N(G)-nitro-D-arginine methyl ester, an inactive isomer of L-NAME, exhibited no such effect. When L- NAME was administered acutely before the challenge injection of MAP, behavioral sensitization was also attenuated only when the dose of L-NAME was high. Coadministration of L-NAME with MAP did not block the development of sensitization to MAP. We also examined whether MAP-induced behavioral sensitization and enhancement of DA release could be observed in vivo in a microdialysis experiment. Challenge injection of MAP caused marked enhancement of DA release in MAP-sensitized rats compared with saline- treated controls corresponding to robust augmentation of locomotor activity. When L-NAME was injected during the MAP withdrawal period, the enhancement of DA release and locomotor activity induced by challenge injection of MAP were attenuated. These results suggest that NO production plays a role in the maintenance (expression) of MAP-induced behavioral sensitization and enhancement of DA release but not in the development of these effects.

Original languageEnglish
Pages (from-to)1424-1430
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume277
Issue number3
Publication statusPublished - 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology

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