Antagonism of the discriminative and aversive stimulus properties of nicotine in C57BL/6J mice.
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.
Gommans
J
J
Section of Behavioural Pharmacology, Institute of Psychiatry, King's College London, De Crespigny Park, SE5 8AF, London, UK.
Stolerman
I P
IP
Shoaib
M
M
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects; D012054:Reinforcement, Psychology; D013649:Taste / Q000187:drug effects
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D000157:Aconitine