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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)