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The Effect of Tryptophan Depletion on the Action of Haloperidol in MK-801-treated Rats

The Effect of Tryptophan Depletion on the Action of Haloperidol in MK-801-treated Rats

Vera Bubeníková, Jirí Horácek, Jirí Kozený, Veronika Platilová, Lucie Závesická, Tomás Pálenícek, Cyril Höschl

Eur J Pharmacol. 2004 Oct 11;502(1-2):109-16.

PMID: 15464096

Abstract:

We investigated the effect of tryptophan depletion (tryptophan-free mixture) on locomotor activity in an animal model of schizophrenia, induced by acute administration of 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801), and the influence of the tryptophan-free mixture on the action of the typical antipsychotic haloperidol. Male rats were pre-treated with haloperidol 60 min after receiving the tryptophan-free mixture (or water). We measured total distance travelled in an open field during a 90-min period. Administration of the tryptophan-free mixture resulted in decreased levels of tryptophan, serotonin and its metabolite 5-hydroxyindolacetic acid in the frontal cortex. Serotonin depletion increased the total distance travelled by MK-801-treated rats, modified the inhibitory effect of haloperidol and normalized the locomotor activity pattern in the model of schizophrenia-like behaviour. The effect of the tryptophan-free mixture combined with the classical antipsychotic haloperidol in MK-801-treated rats indicates the possibly important role of the serotonergic system in the action of antipsychotics.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP18525252	Serotonin hydrogen maleate		18525-25-2	Price

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