Serotonergic neurotransmission mediates hypothermia induced by the N-phenylpiperazine antipsychotic prototypes LASSBio-579 and LASSBio-581.
Pharmacol Biochem Behav
; 89(1): 23-30, 2008 Mar.
Article
em En
| MEDLINE
| ID: mdl-18082872
ABSTRACT
Previous studies have demonstrated that LASSBio-579 and LASSBio-581, two N-phenylpiperazine derivatives designed for the treatment of schizophrenia, are presynaptic dopamine D(2) receptor agonists that induce a hypothermic effect in mice that is not mediated by dopamine receptor activation. The aim of the present study was to investigate possible serotonergic mechanisms underlying hypothermia induced by LASSBio-579 and LASSBio-581 in CF1 mice. The reduction in core temperature was dose-dependent (15-60 mg/kg, i.p.) and occurred by the oral route (30 mg/kg). Pretreatment with haloperidol (4 mg/kg, i.p.) resulted in a synergistic hypothermic effect. Pretreatment with (+/-)DOI (0.25 mg/kg, i.p.), a serotonin 5-HT(2A/C) receptor agonist, reduced the hypothermic effect induced by LASSBio-579 and LASSBio-581 at 15 and 30 mg/kg, i.p. In contrast, (+/-)DOI enhanced the hypothermia induced by both compounds at 60 mg/kg, i.p. The serotonin 5-HT1A antagonist WAY 100635 (0.05 mg/kg, s.c.) abolished the hypothermia induced by LASSBio-579 and diminished the hypothermia induced by LASSBio-581. Pretreatment with LASSBio579 (30 and 60 mg/kg, i.p.) and LASSBio-581 (60 mg/kg, i.p.) reduced the number of head-twitches induced by (+/-)DOI (2.5 mg/kg, i.p.). The ear-scratch response induced by (+/-)DOI was inhibited by both LASSBio-579 and LASSBio-581 at 60 mg/kg, i.p. These results indicate that LASSBio-579 and LASSBio-581 have mechanisms of action through the serotonergic neurotransmitter system.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Antipsicóticos
/
Serotonina
/
Transmissão Sináptica
/
Hipotermia
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Biochem Behav
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Brasil