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Eur J Pharmacol. 2006 Aug 21;544(1-3):69-76. Epub 2006 Jun 28.

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

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H. Lundbeck A/S, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark.


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.

[Indexed for MEDLINE]

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