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N-methyl-D-asparate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) glutamate-receptor antagonist have different interactionswith discriminative stimuli of abused drugs

journal contribution
posted on 2023-06-07, 18:50 authored by Anne Jackson, Geraldine Brown, David N Stephens
The effects of the AMPA-receptor antagonists NBQX and GYKI 52466 were compared with those of the NMDA-receptor channel blocker dizocilpine in two drug discrimination tests. In the first, rats were trained to discriminate morphine (2 mg/kg) from saline and in the second, to discriminate ketamine (7 mg/kg) from saline, using a two-lever food reinforced method. NBQX (1-6 mg/kg) did not substitute for either morphine or ketamine, even at a dose which reduced response rates (6 mg/kg). Likewise, the noncompetitive antagonist GYKI 52466 (5 and 10 mg/kg) produced only saline lever responding in the ketamine trained rats. When tested in combination with the training drug, NBQX (4.5 mg/kg) did not alter the morphine generalisation gradient, and similarly, neither NBQX (3 mg/kg) nor GYKI 52466 (5 and 10 mg/kg) interacted with the ketamine cue. In contrast, dizocilpine (0.05 mg/kg) significantly disrupted discrimination of morphine and produced clear drug lever responding (0.0125-0.1 mg/kg) in ketamine trained rats. These results suggest that AMPA-receptor antagonists and non-competitive NMDA-antagonists have different stimulus properties.

History

Publication status

  • Published

Journal

Psychopharmacology

ISSN

0033-3158

Publisher

Springer

Issue

3

Volume

128

Page range

320-327

ISBN

0033-3158

Department affiliated with

  • Psychology Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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