Classical as well as novel antipsychotic drugs increase self-stimulation threshold in the rat--similar mechanism of action?

Full Abstract

Antipsychotic drugs given acutely increase the threshold for intracranial self-stimulation elicited from the ventral tegmental area. As all the antipsychotic drugs share the dopamine D2-receptor antagonism it is reasonable to believe that this is the cause for suppression of intracranial self-stimulation behaviour. The objective of this investigation was to examine the effect of classical (haloperidol) as well as novel antipsychotic drugs (clozapine, olanzapine and sertindole) on intracranial self-stimulation behaviour. Furthermore, the effects of different specific receptor antagonists on intracranial self-stimulation behaviour were examined. Our results showed that both the classical (haloperidol) and the three novel antipsychotic drugs increase the threshold for intracranial self-stimulation. The results obtained with the receptor specific antagonists showed that dopamine D2, alpha1-adrenoceptor and serotonin 5-HT2A receptor antagonisms inhibit intracranial self-stimulation behaviour and that muscarinic receptor antagonism is without effect. Even though all the tested antipsychotic drugs inhibited intracranial self-stimulation behaviour, there seems to be a difference in their ratio between doses that inhibits intracranial self-stimulation behaviour and those that produce antipsychotic effect in a preclinical model (amphetamine hyperactivity). Sertindole was the only antipsychotic drug able to produce antipsychotic effect without significant inhibition of intracranial self-stimulation behaviour at a narrow dose interval. The remaining antipsychotic drugs all inhibited intracranial self-stimulation behaviour at equal or lower doses than those producing antipsychotic effect.

Learn Faster Today Improve your study skills

Author information

Author/s: Flagstad, Peter (P); Arnt, Jørn (J); Olsen, Christina K (CK);

Affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark. PFLA(-atsign-)Lundbeck.com

Journal and publication information

Publication Type: Journal Article

Journal: European journal of pharmacology (Eur J Pharmacol), published in Netherlands. (Language: eng)

Reference: 2006-Aug; vol 544 (issue 1-3) : pp 69-76

Dates: Created 2006/08/07; Completed 2007/01/12;

PMID: 16860313, status: MEDLINE (last retrieval date: 12/26/2008)

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

External Links for this article (including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Antipsychotic Agents - pharmacology
Behavior, Animal - drug effects
Dose-Response Relationship, Drug
Haloperidol - pharmacology
Male
Motivation

Motivation
Rats
Rats, Wistar
Receptors, Adrenergic, alpha-1 - metabolism
Receptors, Dopamine D2 - metabolism
Receptors, Serotonin - metabolism
Self Stimulation

Associated Chemicals: Antipsychotic Agents (0) ; Receptors, Adrenergic, alpha-1 (0) ; Receptors, Dopamine D2 (0) ; Receptors, Serotonin (0) ; serotonin 5 receptor (0) ; Haloperidol (52-86-8)

These are the highest related articles currently in the database:

See 100+ related articles.