Portal de Periódicos da CAPES

Effects of the novel 5-HT1A receptor antagonist, (+)-way 100135, on stereotyped behaviour induced by the NMDA receptor antagonist dizocilpine in rats

1993; Elsevier BV; Volume: 242; Issue: 1 Linguagem: Inglês

10.1016/0014-2999(93)90015-a

1879-0712

Wolfgang Löscher, Dagmar Hönack,

Ion channel regulation and function

We have recently shown that the stereotyped behaviour induced by the uncompetitive NMDA receptor antagonist dizocilpine (MK-801) can be attenuated or blocked by partial agonists at 5-HT receptors of the 5HT1A subtype, indicating that 5-HT (5-hydroxytryptamine, serotonin) is involved in the stereotyped behaviour produced by dizocilpine. In the present experiment, a selective, silent 5-HT1A receptor antagonist, (+)-WAY 100135 (N-tert-butyl 3-4(2-methoxyphenyl) piperazin 1-yl-2-phenylpropanamide dihydrochloride), was used to further study the role of 5-HT activation in dizocilpine-induced behaviours. At a dose of 10 mg/kg, (+)-WAY 100135 significantly reduced the intensity of head weaving induced by dizocilpine, but this effect was lost by increasing the dose to 20 mg/kg. At this higher dose, (+)-WAY 100135 induced marked but short-lasting increases in skeletal muscle tone and hindlimb abduction, resembling components of the '5-HT behavioural syndrome', which would explain its biphasic effects on dizocilpine induced behaviours. The data substantiate that, in addition to the well known activation of dopaminergic transmission, activation of the 5-HT system might be involved in the behavioural effects of NMDA receptor antagonists such as dizocilpine.