Antagonism of the discriminative and aversive stimulus properties of nicotine in C57BL/6J mice

Neuropharmacology. 2000 Oct;39(13):2840-7. doi: 10.1016/s0028-3908(00)00130-1.


Mice of the C56BL/6J strain were trained to discriminate between nicotine (1.2 mg/kg) and saline in a two-lever drug discrimination procedure under a tandem variable-interval 60 s fixed-ratio 10 schedule of food reinforcement. Mice of the same strain were trained in conditioned taste aversion (CTA) experiments where drinking a saccharin or saline solution was paired with injection of nicotine or vehicle. During testing with both flavours presented simultaneously, a reduction in the intake of the nicotine-paired solution indicated CTA. The nicotine discrimination was acquired successfully and nicotine yielded a steep dose-response curve. The competitive nicotinic antagonist dihydro-beta-erythroidine (DHbetaE, 0.6-3.0 mg/kg) shifted the dose-response for the discriminative stimulus effect of nicotine to the right; the alpha7 nicotinic receptor antagonist methyllycaconitine (MLA, 1.0-10 mg/kg) had no effect. The mice showed strong CTA to 2.0 mg/kg of nicotine and marginally to 0.6 and 1.2 mg/kg of nicotine. DHbetaE (3.0-5.6 mg/kg) attenuated the CTA while MLA (1.0-10 mg/kg) had no effect. These studies show that nicotine has discriminative and aversive stimulus properties in C57BL/6J mice and that the effects are mediated primarily by receptors sensitive to DHbetaE; there was no evidence for the involvement of alpha7 nicotinic receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitine / analogs & derivatives
  • Aconitine / pharmacology
  • Animals
  • Avoidance Learning / drug effects*
  • Behavior, Animal / drug effects
  • Dihydro-beta-Erythroidine / pharmacology
  • Discrimination Learning / drug effects
  • Discrimination, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / antagonists & inhibitors*
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Antagonists / pharmacology
  • Receptors, Nicotinic / drug effects
  • Reinforcement, Psychology
  • Taste / drug effects


  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • methyllycaconitine
  • Dihydro-beta-Erythroidine
  • Nicotine
  • Aconitine