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Research ArticleNEUROPHARMACOLOGY

Lobeline Attenuates d-Methamphetamine Self-Administration in Rats

Steven B. Harrod, Linda P. Dwoskin, Peter A. Crooks, Jennifer E. Klebaur and Michael T. Bardo
Journal of Pharmacology and Experimental Therapeutics July 2001, 298 (1) 172-179;
Steven B. Harrod
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Linda P. Dwoskin
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Peter A. Crooks
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Jennifer E. Klebaur
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Michael T. Bardo
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Abstract

α-Lobeline inhibits d-amphetamine-evoked dopamine release from striatal slices in vitro, appearing to reduce the cytosolic pool of dopamine available for reverse transport by the dopamine transporter. Based on this neurochemical mechanism of action, the present study determined if lobeline decreasesd-methamphetamine self-administration. Rats were surgically implanted with jugular catheters and were trained to lever press on a fixed ratio 5 schedule for intravenousd-methamphetamine (0.05 mg/kg/infusion). To assess the specificity of the effect of lobeline, another group of rats was trained to lever press on a fixed ratio 5 schedule for sucrose reinforcement. Pretreatment of rats with lobeline (0.3–3.0 mg/kg, 15 min prior to the session) decreased responding for bothd-methamphetamine and sucrose reinforcement. Following repeated lobeline (3.0 mg/kg) administration, tolerance developed to the decrease in responding for sucrose; however, the lobeline-induced decrease in responding for d-methamphetamine persisted. Furthermore, the lobeline-induced decrease in responding ford-methamphetamine was not surmounted by increasing the unit dose of d-methamphetamine. These results suggest that lobeline produces a nonspecific rate suppressant effect following acute administration, to which tolerance develops following repeated administration. Importantly, the results also suggest that repeated administration of lobeline specifically decreases responding ford-methamphetamine in a noncompetitive manner. Thus, lobeline may be an effective, novel pharmacotherapy ford-methamphetamine abuse.

Footnotes

  • This work was supported by National Institutes of Health Grants DA00399 (to L.P.D.), DA06018 (to S.B.H.), DA07304 (to S.B.H.), and DA13519, and by a grant from the Tobacco and Health Research Institute, Lexington, KY.

  • Abbreviations:
    DTBZ
    dihydrotetrabenazine
    VMAT2
    vesicular monoamine transporter
    HPLC-EC
    high-performance liquid chromatography with electrochemical detection
    ANOVA
    analysis of variance
    • Received December 18, 2000.
    • Accepted March 20, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 1
1 Jul 2001
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Research ArticleNEUROPHARMACOLOGY

Lobeline Attenuates d-Methamphetamine Self-Administration in Rats

Steven B. Harrod, Linda P. Dwoskin, Peter A. Crooks, Jennifer E. Klebaur and Michael T. Bardo
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 172-179;

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Research ArticleNEUROPHARMACOLOGY

Lobeline Attenuates d-Methamphetamine Self-Administration in Rats

Steven B. Harrod, Linda P. Dwoskin, Peter A. Crooks, Jennifer E. Klebaur and Michael T. Bardo
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 172-179;
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