The effect of tryptophan depletion on the action of haloperidol in MK-801-treated rats.
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.
Prague Psychiatric Center and Center of Neuropsychiatric Studies, 181 03-Prague 8, Czech Republic. bubenikova@pcp.lf3.cuni.cz
Vera
V
Bubeníková
Jirí
J
Horácek
Jirí
J
Kozený
Veronika
V
Platilová
Lucie
L
Závesická
Tomás
T
Pálenícek
Cyril
C
Höschl
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000172:deficiency* / Q000235:genetics*
D012701:Serotonin; D016291:Dizocilpine Maleate; D014364:Tryptophan; D006220:Haloperidol