An examination of NMDA receptor contribution to conditioned responding evoked by the conditional stimulus effects of nicotine

Jennifer E. Murray, Andrew W. Walker, Robert J. Polewan, Rick A. Bevins

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Rationale: Research using a drug discriminated goal-tracking (DGT) task showed that the N-methyl-d-aspartate (NMDA) channel blocker MK-801 (dizocilpine) reduced the nicotine-evoked conditioned response (CR). Objectives: Given the unknown mechanism of the effect, Experiment 1 replicated the MK-801 results and included tests with NMDA receptor ligands. Experiments 2a and 2b tested whether MK-801 pretreatment blocked DGT via a state-dependency effect. Methods: In Experiment 1, adult male Sprague-Dawley rats received intermittent access to liquid sucrose following nicotine (0.4 mg base/kg); no sucrose was delivered on intermixed saline sessions. Conditioning was indicated by increased anticipatory dipper entries (goal-tracking) on nicotine compared to saline sessions. Antagonism and/or substitution tests were conducted with MK-801, phencyclidine, CGP 39551, d-CPPene (SDZ EAA 494), Ro 25,6981, L-701,324, ACPC, and NMDA. In Experiment 2a, rats received nicotine and sucrose on every session-no intermixed saline sessions without sucrose. Tests combined MK-801 or the non-competitive nicotinic acetylcholine receptor antagonist, mecamylamine with either nicotine or saline. Experiment 2b had sucrose delivered on saline sessions and no sucrose on intermixed nicotine sessions followed by MK-801 antagonism tests of the saline CS. Results: MK-801 and phencyclidine dose-dependently attenuated the CR in Experiment 1. Ro-25,6981 enhanced the CR, but did not substitute for nicotine. Other ligands showed inconsistent effects. In Experiment 2a, MK-801 pretreatment reduced goal-tracking when given before nicotine and saline test sessions; mecamylamine pretreatment had no effect. In Experiment 2b, MK-801 dose-dependently attenuated the saline-evoked CR. Conclusions: Combined, the results suggest that MK-801 blocks discriminated goal-tracking by virtue of state-changing properties.

Original languageEnglish (US)
Pages (from-to)131-141
Number of pages11
Issue number1
StatePublished - Jan 2011


  • Appetitive Pavlovian conditioning
  • Discriminated goal-tracking
  • Drug discrimination
  • Mecamylamine
  • NMDA
  • NR2B
  • Smoking
  • State-dependent learning
  • Tobacco addiction

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'An examination of NMDA receptor contribution to conditioned responding evoked by the conditional stimulus effects of nicotine'. Together they form a unique fingerprint.

Cite this