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Clozapine as a dopamine D₁ receptor agonist
Stockholm University, Faculty of Social Sciences, Department of Psychology.
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Objectives'. The present study had two major objectives; [1] to examine the specific role of dopamine D, and DM receptors in body temperature regulation in rats, and [2] to examine in vivo dopamine D, and Dm receptor agonist/antagonist properties of clozapine by use of core temperature measurements.

Methods'. Body temperature homeostasis is known to be regulated via a number of neurotransmitters, including dopamine, noradrenaline, serotonin and acetylcholine. Thus, core temperature measurements have been used to investigate in vivo actions of clozapine as an agonist/antagonist at various receptor subtypes of these neurotransmitters.

Results'. A new finding in the present series of experiments was the observation that the selective dopamine D1 receptor agonists A 68930 and dihydrexidine produce hypothermia in rats. This effect is distinct from hypothermia produced by the dopamine Dj, receptor agonists quinpirole and 7-OH-DPAT. Thus, these dopamine D, and DM receptor agonists interact in an additive, rather than a synergistic or antagoniste, manner, suggesting specific and independent roles of dopamine D, and DM receptors involved in body temperature regulation in rats. The dopamine D, or Dm receptor agonist-induced hypothermia could not be antagonized by the administration of clozapine (0.6 mg kg-1). At higher doses (2.5-10.0 mg kg“1), clozapine produced hypothermia that could be antagonized by selective dopamine D,, but not DM, receptor antagonists, suggesting dopamine Dt receptor agonist properties of clozapine at receptors involved in temperature regulation in rats. As expected, in this core temperature model clozapine displayed properties as a 5-HT2A and a, adrenergic receptor antagonist. In the present model, there were no, or much weaker, effects of clozapine as an agonist/antagonist at 5-HT1A, or, adrenergic or muscarinic receptors.

Conclusions'. The present study shows that clozapine displays in vivo properties as a dopamine D, receptor agonist. The effects of clozapine, and known dopamine D, receptor ligands, in Parkinsons disease and in schizophrenia, are in agreement with the notion that intrinsic efficacy of clozapine at brain dopamine D, receptors may contribute to its atypical clinical profile as an antipsychotic agent.

Place, publisher, year, edition, pages
Stockholm: Department of Psychology, Stockholm University , 1998. , p. 44
Research subject
Psychology
Identifiers
URN: urn:nbn:se:su:diva-39142ISBN: 91-7153-718-X (print)OAI: oai:DiVA.org:su-39142DiVA, id: diva2:318758
Public defence
1998-03-05, Sal U31, psykologiska institutionen, Frescati Hagväg 8, Stockholm, 10:00 (English)
Opponent
Note

Härtill 6 uppsatser

Available from: 2010-05-10 Created: 2010-05-10 Last updated: 2018-05-24Bibliographically approved

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