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


OBJECTIVE
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.
Murray
Jennifer E
JE
Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588-0308, USA. jem98@cam.ac.uk
Walker
Andrew W
AW
Polewan
Robert J
RJ
Bevins
Rick A
RA
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003517:Cyclopentanes / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
C554503:(1S,2S)-2-aminocyclopentane-1-carboxylic acid; D003517:Cyclopentanes; D018691:Excitatory Amino Acid Antagonists; D010636:Phenols; D010879:Piperazines; D010880:Piperidines; D015363:Quinolones; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; C064540:CGP 39551; C065286:SDZ EAA 494; D016202:N-Methylaspartate; D008464:Mecamylamine; D016291:Dizocilpine Maleate; D009538:Nicotine; D015763:2-Amino-5-phosphonovalerate; C094635:L 701324; D010622:Phencyclidine