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

Authors

Jennifer E. Murray, University of Nebraska—LincolnFollow
Andrew W. Walker, University of Nebraska—Lincoln
Robert J. Polewan, University of Nebraska—Lincoln
Rick A. Bevins, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2011

Citation

Psychopharmacology (Berl). 2011 January ; 213(1): 131–141.

Comments

© Springer-Verlag 2010

Abstract

Rationale—Research using a drug discriminated goal-tracking (DGT) task showed that the Nmethyl- 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.