CNQX but not NBQX Prevents Expression of Amphetamine-Induced Place Preference Conditioning: A Role for the Glycine Site of the NMDA Receptor, but not AMPA Receptors1
Abstract
We investigated the role of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor in the induction and expression of an amphetamine-induced conditioned place preference (CPP) in mice. The selective AMPA-receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) failed to prevent the induction of a CPP, except at a dose (30 mg/kg) that also produced a conditioned place aversion. NBQX also failed to affect the expression of a CPP at a dose high enough to reduce activity levels. In contrast, the less selective AMPA receptor antagonist 6-cyano-7-nitroquinoxalone-2,3-dione (CNQX) prevented the expression of a CPP at doses (1–10 mg/kg) that had no effect on activity levels. We therefore tested the possibility that CNQX exerted its effects due to antagonism at the glycine site of theN-methyl-d-aspartate receptor. The glycine-site antagonist 7-chloro-4-hydroxy-3-(2-phenoxy)phenyl-2(1H)-quinolone also prevented the expression of a CPP at doses that had no effect on activity levels (0.1–0.3 mg/kg). These results suggest that neither the induction nor the expression of an amphetamine-induced CPP requires AMPA receptor-mediated transmission and that effects found in previous studies using the less selective AMPA receptor antagonists may be due to the effects of these compounds at the glycine site of the N-methyl-d-aspartate receptor.
Footnotes
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Send reprint requests to: Dr. D. N. Stephens, Laboratory of Experimental Psychology, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom. E-mail:dns{at}epunix.biols.susx.ac.uk
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↵1 This work was supported by the Ernst Schering Forschungsgesellschaft, Berlin.
- Abbreviations:
- AMPH
- amphetamine
- CPP
- conditioned place preference
- NBQX
- 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline
- CPA
- conditioned place aversion
- AMPA
- α-amino-3-hydroxy-5-methyl-4-isoxazole propionate
- DNQX
- 6,7-dinitroquinoxaline-2,3-dione
- CNQX
- 6-cyano-7-nitroquinoxalone-2,3-dione
- L-701,324
- 7-chloro-4-hydroxy-3-(2-phenoxy)phenyl-2(1H)-quinolone
- GYKI 52466
- 1-(4-aminophenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazepine
- NMDA
- N-methyl-d-aspartate
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- Received November 24, 1998.
- Accepted February 28, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
