Prior reproductive experience alters prolactin-induced macrophage responses in pregnant rats.

Reproductive experience (i.e., pregnancy and lactation) induces physiological changes in mammals. A previous reproductive experience was recently shown to modulate the activity of dopaminergic hypothalamic systems while decreasing serum prolactin levels and oxidative burst activity in peritoneal macrophages. Dopamine receptor antagonists increase serum prolactin levels, and both prolactin and dopamine receptors may be involved in the modulation of macrophage activity, providing a means of communication between the nervous and immune systems. The present study evaluated the in vitro effects of prolactin and a dopamine D2 receptor antagonist on the peritoneal activity of macrophages from primigravid and multigravid female rats during the third trimester of pregnancy. Oxidative bursts and phagocytosis in peritoneal macrophages were evaluated by flow cytometry. Primigravid and multigravid Wistar rats, during the third trimester of pregnancy (i.e., days 17-21), were used. Peritoneal fluid samples from these rats were first incubated with prolactin (10 and 100 nM) for different periods of time. The same procedure was repeated to evaluate the effects of domperidone (10 and 100 nM) on macrophage activity. Our results showed that macrophages from multigravid rats responded more effectively to in vitro incubation with prolactin, especially with regard to the intensity and percentage of phagocytosis. Additionally, these effects were more pronounced after incubation periods of 30 min or 4 h. These data suggest that macrophages during a second pregnancy become more sensitive to the phagocytotic effects of prolactin.

Prolactin differentially modulates the macrophage activity of lactating rats: possible role of reproductive experience.

Reproductive experience (i.e., pregnancy and lactation) induces physiological changes in mammals. We recently showed that a previous reproductive experience can modulate the activity of dopaminergic hypothalamic systems while decreasing serum prolactin (PRL) levels and oxidative burst activity in peritoneal macrophages. Dopamine receptor antagonists increase serum PRL levels, and both PRL and dopamine receptors might be involved in the modulation of macrophage activity, providing a means of communication between the nervous and immune systems. The present study evaluated the in vitro effects of PRL and the dopamine receptor D2 antagonist domperidone (DOMP) on the peritoneal activity of macrophages from primiparous and multiparous female rats during lactation. Oxidative bursts and phagocytosis in peritoneal macrophages were evaluated by flow cytometry. Primiparous and multiparous Wistar rats, during the period of lactation (i.e., days 5-7 after parturition) were used. Samples of peritoneal fluid from these rats were first incubated with PRL (10 and 100 nM) for different periods of time. The same procedure was repeated to evaluate the effects of DOMP (10 and 100 nM). Our results showed that macrophages from multiparous rats respond more effectively to in vitro incubation with PRL, especially with regard to oxidative bursts and the percentage of phagocytosis. Additionally, these effects were more pronounced after 30 min of incubation. These data suggest that reproductive experience is associated with a reduction in serum PRL levels, and cells in experienced female animals, including their macrophages, become more sensitive to the effects of PRL.

Hiperprolactinemia e atividade de macrófagos peritoneias de ratas: influência da experiência reprodutiva / Hyperprolactinemia and macrophage activity of female rats: reproductive experience influences

A experiência reprodutiva (ER) é um evento relevante na vida de uma fêmea e pode ser descrita como uma rica experiência social e hormonal. A ER influencia tanto o metabolismo como as concentrações séricas de estrógenos, cortisol e prolactina (PRL), sendo que a liberação desta é dramaticamente influenciada pelo parto e sua inibição depende da ativação do receptor adenohipofisário de dopamina (DA) em conseqüência do aumento da atividade neuronal dopaminérgica tubero-infundibular. A literatura sugere que o sistema dopaminérgico pode ser influenciado pela ER, pois em roedores resulta em aumento da atividade dopaminérgica tanto no lobo frontal quanto em regiões hipotalâmicas. Por outro lado, a hipófise apresenta um papel importante na regulação do crescimento, diferenciação e função de todas as células do organismo, incluindo as células do sistema imune. Assim, a comunicação recíproca entre os sistemas neuroendócrino e imune é crítica para o estabelecimento do equilíbrio dinâmico e mecanismos de defesa do organismo. Neste contexto, existem vários fatores que demonstram a existência de uma interação entre esses sistemas por meio da ação da PRL, entre os quais pode-se ressaltar: a existência de receptores para esse hormônio em linfócitos B e T e monócitos de humanos, a secreção de PRL pelos linfócitos e evidências sobre o papel da PRL na regulação das respostas humoral e celular. Diante do exposto, o objetivo do presente trabalho foi estudar os efeitos da PRL sobre a atividade de macrófagos peritoneais em ratas adultas com hiperprolactinemia induzida farmacologicamente, e avaliar a influência da experiência reprodutiva sobre estes parâmetros. Para tanto, utilizou-se a citometria de fluxo e abordagens neuroquímicas. Os resultados mostram que: a) o esquema de tratamento com a DOMP (2,5 mg/kg), compreendendo 12 horas entre duas administrações, provoca aumento na geração do burst oxidativo, tanto espontâneo, quanto induzido pelo éster de forbol (PMA), assim como na intensidade e na porcentagem de fagocitose; b) este tratamento induz a hiperprolactinemia em ratas virgens adultas; c) Uma hora de hiperprolactinemia induzida por DOMP não altera significativamente a atividade de macrófagos; d) O tratamento in vitro com a PRL nas concentrações de 10 e 100 nM altera de forma diferenciada o burst oxidativo e a fagocitose de macrófagos peritoneais, de forma bifásica e tempodependente...(AU)

Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L.

Citrus aurantium L. is commonly used as an alternative treatment for insomnia, anxiety and epilepsy. Essential oil from peel (EOP) and hydroethanolic (70% w/v) extract (HE) from leaves were obtained. Hexanic (HF), dichloromethanic (DF) and final aqueous (AF) fractions were obtained from HE by successive partitions. Swiss male mice (35-45 g) were treated orally with 0.5 or 1.0 g/kg of these preparations 30 min before the experiments for the evaluation of the sedative/hypnotic activity (sleeping time induced by sodium pentobarbital - SPB: 40 mg/kg, i.p.), anxiolytic activity (elevated plus maze--EPM) and anticonvulsant activity (induced by pentylenetetrazole--PTZ: 85 mg/kg, sc or by maximal electroshock--MES: 50 mA, 0.11 s, corneal). The results showed that EOP (0.5 g/kg) increased the latency period of tonic seizures in both convulsing experimental models. This effect was not dose-dependent. Treatment with 1.0 g/kg increased the sleeping time induced by barbiturates and the time spent in the open arms of the EPM. Specific tests indicated that the preparation, in both doses used, did not promote deficits in general activity or motor coordination. HF and DF fractions (1.0 g/kg) did not interfere in the epileptic seizures, but were able to enhance the sleeping time induced by barbiturates. The results obtained with EOP in the anxiety model, and with EOP, HF and DF in the sedation model, are in accord with the ethnopharmacological use of Citrus aurantium L., which could be useful in primary medical care, after toxicological investigation.