Lobeline does not serve as a reinforcer in rats

Steven B. Harrod, Linda P. Dwoskin, Thomas A. Green, Brenda J. Gehrke, Michael T. Bardo

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Rationale: Previous results demonstrated that pretreatment with lobeline attenuates d-methamphetamine self-administration in rats. Objective: The present experiments determined if lobeline serves as a reinforcer, if it decreases d-methamphetamine-induced reinstatement of d-methamphetamine self-administration, and if it activates the mesolimbic and nigrostriatal dopamine (DA) pathways in Sprague-Dawley male rats. Methods: The ability of intravenous (IV) lobeline (0.015-0.15 mg/kg per infusion) to engender responding and the ability of lobeline (0.015 and 0.05 mg/kg per infusion) to substitute for d-methamphetamine was determined using the self-administration paradigm. Experiments were also performed to determine if lobeline (1.0 and 3.0 mg/kg) reinstates responding for d-methamphetamine or alters the ability of d-methamphetamine (1.0 mg/kg per infusion) to reinstate responding following extinction. The effect of lobeline (3.0 mg/kg) or d-methamphetamine (1.0 and 3.0 mg/kg) on DA and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and striatum were also determined. Results: Lobeline was not self-administered and did not substitute for d-methamphetamine. Also, lobeline did not reinstate responding for d-methamphetamine following extinction nor did it alter d-methamphetamine-induced reinstatement. Furthermore, lobeline did not alter DA or DOPAC levels in the either the nucleus accumbens or striatum. Conclusions: Taken together, the present results indicate that lobeline decreases d-methamphetamine self-administration by decreasing reward, not by acting as a substitute reinforcer.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
Issue number4
StatePublished - Feb 2003

Bibliographical note

Funding Information:
Acknowledgements We thank Y. Shaham for his critical discussion of the design of the present experiments. We gratefully acknowledge the expert technical assistance of S. Phillips and N. Benjamin. The use of LOB for the treatment of psychostimulant abuse is protected by US Patent No. 5,830,904, which is assigned to the University of Kentucky. A potential royalty stream may result to L.P.D. as determined by University arrangements. This work was supported by NIH grants DA00399 (L.P.D.), DA06018 (S.B.H.), DA13519 (L.P.D., M.T.B.).


  • Drug abuse
  • Extinction
  • Lobeline
  • Reinstatement
  • Self-administration
  • d-Methamphetamine

ASJC Scopus subject areas

  • Pharmacology


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