Lobeline inhibits nicotine-evoked [3H]dopamine overflow from rat striatal slices and nicotine-evoked 86Rb+ efflux from thalamic synaptosomes

Dennis K. Miller, Peter A. Crooks, Linda P. Dwoskin

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


The present study evaluated the interaction of lobeline with neuronal nicotinic acetylcholine receptors using two in vitro assays, [3H] overflow from [3H]dopamine ([3H]DA)-preloaded rat striatal slices and 86Rb+ efflux from rat thalamic synaptosomes. To assess agonist interactions, the effect of lobeline was determined and compared to S(-)-nicotine. To assess antagonist interactions, the ability of lobeline to inhibit the effect of S(-)-nicotine was determined. Both S(-)-nicotine (0.1-1 μM) and lobeline (>1.0 μM) evoked [3H] overflow from superfused [3H]DA-preloaded striatal slices. However, lobeline-evoked [3H] overflow is mecamylamine-insensitive, indicating that this response is not mediated by nicotinic receptors. Moreover, at concentrations (<1.0 μM) which did not evoke [3H] overflow, lobeline inhibited S(-)-nicotine (0.1-10 μM)-evoked [3H] overflow, shifting the S(-)-nicotine concentration-response curve to the right. S(-)-Nicotine (30 nM-300 μM) increased (EC50 value=0.2 μM) 86Rb+ efflux from thalamic synaptosomes. In contrast, lobeline (1 nM-10 μM) did not evoke 86Rb+ efflux, and the lack of intrinsic activity indicates that lobeline is not an agonist at this nicotinic receptor subtype. Lobeline completely inhibited (IC50 value=0.7 μM) 86Rb+ efflux evoked by 1 μM S(-)-nicotine, a concentration which maximally stimulated 86Rb+ efflux. Thus, the results of these in vitro experiments demonstrate that lobeline inhibits the effects of S(-)-nicotine, and suggest that lobeline acts as a nicotinic receptor antagonist. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)2654-2662
Number of pages9
Issue number13
StatePublished - 2000

Bibliographical note

Funding Information:
This study was supported by NIH grants F32 DA06043 and DA13519, and an NIEHS Training Grant ES07266 and by a grant from the Tobacco and Health Research Institute, Lexington, Kentucky. The authors thank Lincoln Wilkins and Susan Buxton for their technical assistance.


  • Dopamine release
  • Lobeline
  • Nicotine
  • Nicotinic receptors
  • Rb efflux

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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