Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats.
BACKGROUND
Recent studies have demonstrated that nicotine can enhance operant responding for other nonpharmacological reinforcing stimuli. However, the nature of the reinforcement-enhancing effect of nicotine remains largely unknown.


OBJECTIVE
The present study determined the dose dependency of the ability of nicotine to increase lever-pressing responses maintained by a compound visual stimulus (VS) in rats and examined its sensitivity to pharmacological antagonism of nicotinic acetylcholine receptors (nAChRs).


METHODS
Male Sprague-Dawley rats were trained in daily 1-h sessions to lever press for delivery of a VS (1 s lever light on and 60 s house light off) on a fixed ratio 5 schedule. During these sessions, eight scheduled response-independent intravenous infusions of nicotine (total amount: 0, 0.06, 0.12, 0.24, 0.48 mg kg(-1) h(-1)) were delivered. In pharmacological tests, a nonselective nAChR antagonist mecamylamine, alpha4beta2-selective antagonist dihydro-beta-erythroidine (DHbetaE), and alpha7-selective antagonist methyllycaconitine (MLA) were administered in different groups of rats 30 min before the session.


RESULTS
The VS maintained a moderate level of lever-pressing responses and nicotine dose-dependently increased responses for the VS presentations. Preteatment of mecamylamine and DHbetaE but not MLA significantly attenuated the nicotine-enhanced responding. However, mecamylamine had no effect on responding for the VS in rats that received scheduled saline infusions.


CONCLUSIONS
These results demonstrate dose dependency of the reinforcement-enhancing effect of nicotine and suggest that activation of the alpha4beta2- but not alpha7-containing nAChRs may mediate this effect.
Liu
Xiu
X
Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA. xiuliu@pitt.edu
Palmatier
Matthew I
MI
Caggiula
Anthony R
AR
Donny
Eric C
EC
Sved
Alan F
AF
D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D014796:Visual Perception / Q000187:drug effects
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D009538:Nicotine; D000157:Aconitine