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Doctoral Thesis
DOI
10.11606/T.10.2004.tde-12042007-173309
Document
Author
Full name
Geane Antiques Lourenço
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2004
Supervisor
Committee
Dorce, Valquiria Abrão Coronado (President)
Breno, Maria Cristina
Felicio, Luciano Freitas
Florio, Jorge Camilo
Frussa Filho, Roberto
Title in Portuguese
Efeitos do tratamento agudo e prolongado com haloperidol e da retirada abrupta deste tratamento, sobre a atividade de macrófagos peritoneais de ratos machos e fêmeas
Keywords in Portuguese
Coticosterona
Dimorfismo sexual
Haloperidol
Macrófagos
Neuroimunomodulação
Prolactina
Abstract in Portuguese
Haloperidol é um antagonista de receptor D2 de dopamina freqüentemente utilizado na clínica para tratamento de pacientes esquizofrênicos. Haloperidol aumenta a liberação de prolactina pela glândula pituitária anterior, e a prolactina é um fator capaz de modular a atividade do sistema imune. Grupos de seis ratos machos e fêmeas receberam tratamento agudo de 2mg/kg de haloperidol (E1), tratamento prolongado com haloperidol (E2) (2mg/kg/dia por 21 dias); retirada abrupta do tratamento prolongado com haloperidol (E3), ou ainda tratamento agudo com 6mg/kg de haloperidol (E4). Os animais controle receberam tratamento similar com veículo de diluição (grupos C1, C2 e C3 respectivamente). Neste trabalho, o tratamento prolongado com haloperidol (E2) aumentou a atividade de macrófagos, aumentando o espraiamento, a fagocitose e a liberação de NO em ratos machos e fêmeas. O tratamento agudo com 2mg/kg de haloperidol (E1) não foi capaz de alterar a atividade de macrófagos, porém a dose de 6mg/kg (E4) aumentou o espraiamento e a fagocitose. Os tratamentos agudo (E1) e prolongado (E2) com haloperidol aumentaram os níveis plasmáticos de corticosterona e de prolactina tanto em machos quanto em fêmeas. Os macrófagos de ratos machos e fêmeas apresentam os mesmos padrões de alterações após os tratamentos com haloperidol, exceto para produção de H2O2 que foi maior apenas para as fêmeas dos grupos C3 e E3. Discutiu-se de que maneira o haloperidol induz ativação de macrófagos, se por uma forma indireta através do aumento nos níveis de prolactina, ou alternativamente, sendo esta ativação uma conseqüência da ação direta do haloperidol sobre os receptores de dopamina dos macrófagos.
Title in English
Effects of acute, long-term and abrupt withdrawal of long-term haloperidol treatment of the peritone macrophage activity in males and females rats
Keywords in English
Corticosterone
Haloperidol
Macrophages
Neuroimmunomodulation
Prolactin
Sexual dimorphism
Abstract in English
Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received acute 2mg/kg haloperidol treatment (E1), long-term (E2) haloperidol treatment (2mg/kg/day for 21 days); abrupt withdrawal of long-term (E3) haloperidol treatment, or acute 6mg/kg haloperidol treatment (E4). Control rats were treated similarly, but with vehicle (groups C1, C2 and C3 respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. Acute 2mg/kg haloperidol treatment (E1) didn?t change macrophage activity, however, the 6mg/kg dose (E4) increased macrophage spreading and phagocytosis. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments, except for production of H2O2 that was larger just for the females of the groups C3 and E3. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.
 
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Geane_A_Lourenco.pdf (1.35 Mbytes)
Publishing Date
2007-04-27
 
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