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The 5-HT2A receptor antagonist M100907 is more effective in counteracting NMDA antagonist- than dopamine agonist-induced hyperactivity in mice

Artikel i vetenskaplig tidskrift
Författare Maria L. Carlsson
Peter Martin
Marie Nilsson
S. M. Sorensen
Arvid Carlsson
Susanna Waters
Nicholas Waters
Publicerad i J Neural Transm
Volym 106
Nummer/häfte 2
Sidor 123-9
ISSN 0300-9564 (Print)
Publiceringsår 1999
Publicerad vid Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi
Sidor 123-9
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Amphetamine/antagonists & inhibitors/pharmacology, Animals, Dizocilpine Maleate/antagonists & inhibitors/pharmacology, Dopamine/metabolism, Dopamine Agonists/*pharmacology, Dopamine Uptake Inhibitors/pharmacology, Dose-Response Relationship, Drug, Excitatory Amino Acid Antagonists/*pharmacology, Fluorobenzenes/*pharmacology, Glutamic Acid/metabolism, Haloperidol/pharmacology, Hyperkinesis/*chemically induced/metabolism, Male, Mice, Mice, Inbred Strains, Motor Activity/drug effects, N-Methylaspartate/antagonists & inhibitors/*pharmacology, Piperazines/antagonists & inhibitors/pharmacology, Piperidines/*pharmacology, Receptor, Serotonin, 5-HT2A, Receptors, Serotonin/physiology, Serotonin Antagonists/*pharmacology
Ämneskategorier Farmakologi

Sammanfattning

The purpose of the present study was to compare the effectiveness of the selective 5-HT2A antagonist M100907 in different psychosis models. The classical neuroleptic haloperidol was used as reference compound. Two hyperdopaminergia and two hypoglutamatergia mouse models were used. Hyperdopaminergia was produced by the DA releaser d-amphetamine or the DA uptake inhibitor GBR 12909. Hypoglutamatergia was produced by the un-competitive NMDA receptor antagonist MK-801 or the competitive NMDA receptor antagonist D-CPPene. M100907 was found to counteract the locomotor stimulant effects of the NMDA receptor antagonists MK-801 and D-CPPene, but spontaneous locomotion, d-amphetamine- and GBR-12909-induced hyperactivity were not significantly affected. Haloperidol, on the other hand, antagonized both NMDA antagonist- and DA agonist-induced hyperactivity, as well as spontaneous locomotion in the highest dose used. Based on the present and previous results we draw the conclusion that 5-HT2A receptor antagonists are particularly effective against behavioural anomalies resulting from hypoglutamatergia of various origins. The clinical implications of our results and conclusions would be that a 5-HT2A receptor antagonist, due to i a the low side effect liability, could be the preferable treatment strategy in various disorders associated with hypoglutamatergia; such conditions might include schizophrenia, childhood autism and dementia disorders.

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