The role of nicotinic acetylcholine receptors in the primary reinforcing and reinforcement-enhancing effects of nicotine

Neuropsychopharmacology. 2007 May;32(5):1098-108. doi: 10.1038/sj.npp.1301228. Epub 2006 Nov 8.

Abstract

The primary reinforcing effects of nicotine are mediated by the drugs action at central nervous system nicotinic acetylcholine receptors (nAChRs). Although previous studies have demonstrated that nicotine potently enhances responding for non-pharmacological stimuli, the role of nAChRs in this reinforcement-enhancing effect is not known. The two reinforcement-related effects of nicotine can be dissociated in a paradigm that provides concurrent access to drug infusions and a non-pharmacological visual stimulus (VS). The present study characterized the role of nAChRs in the primary reinforcing effect of nicotine and the reinforcement-enhancing effect of nicotine. For rats with access to VS (VS-Only), nicotine (NIC-Only), both reinforcers contingent upon one response (NIC+VS) or both reinforcers contingent upon separate responses (2-Lever), unit dose-response relationships (0, 30, 60, or 90 microg/kg/infusion, free base) were determined over a 22-day acquisition period. Expression of the two reinforcement-related effects of nicotine was manipulated by pharmacological antagonism of nAChRs (1 mg/kg mecamylamine, subcutaneous, 5-min before the session) or by substituting saline for nicotine infusions (ie extinction) over a series of seven test sessions. Unit dose manipulations yielded an inverse dose-response relationship for active lever responding in the NIC+VS group. The dose-response relationships for rats with independent access to each reinforcer (2-Lever group) were relatively flat. For the 2-Lever group, acute mecamylamine challenge blocked the reinforcement-enhancing effects of nicotine, VS-lever responding decreased to basal levels on the first day of mecamylamine treatment or saline substitution (to the level of the VS-Only group). In contrast, nicotine-lever responding decreased gradually over the 7-day testing period (similar to saline extinction). The two reinforcement-related effects of nicotine are mediated by nAChRs but can be dissociated by acute and chronic profiles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Dose-Response Relationship, Drug
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Male
  • Mecamylamine / pharmacology
  • Neuropsychological Tests
  • Nicotine / adverse effects*
  • Nicotinic Agonists / adverse effects
  • Nicotinic Antagonists / pharmacology
  • Photic Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Reinforcement, Psychology*
  • Reward
  • Self Administration
  • Tobacco Use Disorder / metabolism*
  • Tobacco Use Disorder / physiopathology

Substances

  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Mecamylamine
  • Nicotine
  • Acetylcholine