Behavioural and neurochemical interactions of the AMPA antagonist GYKI 52466 and the non-competitive NMDA antagonist dizocilpine in rats.

Full Abstract

The behavioural and neurochemical effects of the N-methyl-D-aspartate (NMDA) antagonist dizocilpine and the alpha-amino-3-hydroxy-5-methylisoxazole- 4-propionic acid (AMPA) antagonist GYKI 52466, given alone or in combination, were investigated in rats. Locomotor activity was increased by dizocilpine (0.2 mg/kg), but not by GYKI 52466 (2.4 mg/kg). Dizocilpine-induced hyperlocomotion was reduced by co-administration of GYKI 52466. In dizocilpine-treated rats dopamine (DA) metabolism (measured as DOPAC [dihydroxyphenylacetic acid] or DOPAC/DA in post mortem brain tissue) was increased in the prefrontal cortex and nucleus accumbens. In GYKI 52466-treated rats serotonin was reduced in the prefrontal cortex and nucleus accumbens while DA metabolism was not affected. In rats treated with dizocilpine plus GYKI 52466, DA metabolism was increased only in the prefrontal cortex, but not in the nucleus accumbens, when compared with vehicle-treated animals. These data confirm that AMPA and NMDA antagonists do not have synergistic effects on locomotor activity. A differential role of NMDA and AMPA antagonists in the control of mesolimbic DA neurons will be discussed here.

Author information

Author/s: Bubser, M (M); Tzschentke, T (T); Hauber, W (W);

Affiliation: Department of Neuropharmacology, University of Tübingen, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neural transmission. General section (J Neural Transm Gen Sect), published in AUSTRIA. (Language: eng)

Reference: 1995-; vol 101 (issue 1-3) : pp 115-26

Dates: Created 1996/09/03; Completed 1996/09/03; Revised 2008/11/21;

PMID: 8695042, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adaptation, Psychological - drug effects
Animals
Anti-Anxiety Agents
Behavior, Animal - drug effects
Benzodiazepines - pharmacology
Brain Chemistry - drug effects
Dizocilpine Maleate - pharmacology
Dopamine - metabolism
Drug Interactions
Excitatory Amino Acid Antagonists - pharmacology

Male
Motor Activity - drug effects
Neostriatum - drug effects; metabolism
Nucleus Accumbens - drug effects; metabolism
Prefrontal Cortex - drug effects; metabolism
Rats
Rats, Sprague-Dawley
Receptors, AMPA - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Serotonin - metabolism

Associated Chemicals: Anti-Anxiety Agents (0) ; Excitatory Amino Acid Antagonists (0) ; Receptors, AMPA (0) ; Receptors, N-Methyl-D-Aspartate (0) ; GYKI 52466 (102771-26-6) ; Benzodiazepines (12794-10-4) ; Serotonin (50-67-9) ; Dopamine (51-61-6) ; Dizocilpine Maleate (77086-22-7)

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