The aim of the present study was to compare the toxic effects of fluoxetine (F) (8 and 16 mg/kg) and venlafaxine (V) (40 and 80 mg/kg) administered during the third week of pregnancy on early development of rats. Both antidepressants were administered by gavage on pregnancy days 15 to 20 to groups of 10 to 12 animals each. Duration of gestation, food and water consumption, number of live pups and birth weight were recorded. Litters were culled to six pups at birth (day 1) and followed for growth until weaning (day 25). On day 60, a male and a female from each litter were injected with the 5-HT 1 agonist, 5-methoxy-N,N-dimethyltryptamine (6 mg/kg, ip) and the serotonergic syndrome was graded. Fluoxetine but not venlafaxine reduced the duration of pregnancy when compared to the control (C) group (F = 21.1 days and C = 21.6 days, mean, P<0.02; maximum = 22 days and minimum = 21 days in both groups). The highest doses of both fluoxetine, 16 mg/kg (F16), and venlafaxine, 80 mg/kg (V80), reduced the food intake of pregnant rats, resulting in different rates of body weight gain during treatment (from pregnancy day 15 to day 20): F16 = 29.0 g, V80 = 28.7 g vs C = 39.5 g (median). Birth weight was influenced by treatment and sex (P<0.05; two-way ANOVA). Both doses of fluoxetine or venlafaxine reduced the body weight of litters; however, the body weight of litters from treated dams was equal to the weight of control litters by the time of weaning. At weaning there was no significant difference in weight between sexes. There was no difference among groups in number of live pups at birth, stillbirths, mortality during the lactation period or in the manifestation of serotonergic syndrome in adult rats. The occurrence of low birth weight among pups born to dams which did not show reduced food ingestion or reduction of body weight gain during treatment with lower doses of fluoxetine or venlafaxine suggests that these drugs may have a deleterious effect on prenatal development when administered during pregnancy. In addition, fluoxetine slightly but significantly affected the duration of pregnancy (about half a day), an effect not observed in the venlafaxine-treated groups.
A role for catecholamines in the regulation of the blood neutrophilia induced by intravenous (i.v.) injection of lipopolysaccharide (LPS; 250 μg/kg) was examined in Wistar rats by means of surgical adrenalectomy or pretreatment with adrenergic and dopaminergic antagonists into naive animals. Treatment of animals with a single dose (250 μg/kg) of LPS caused a dramatic increase in the number of circulating neutrophils concomitant with a decrease in the number of these cells in the bone marrow. These effects were partially reversed when catecholamine stores were depleted with reserpine. It was found that neither adrenalectomy nor pretreatment with the dopaminergic antagonists, chlorpromazine and pimozide, affected the changes in neutrophil counts induced by LPS. The injection of the α1/α2‐adrenoceptor antagonist, phentolamine, and the selective α1‐adrenoceptor antagonist, prazosin, significantly decreased blood neutrophilia induced by LPS. However, neither the selective (α2‐adrenoceptor antagonist, yohimbine, nor the β‐adrenoceptor antagonist, propranolol, had any effect on LPS response. Taken together, these findings support the hypothesis that the catecholamine norepinephrine plays a role in the regulation of the LPS‐induced neutrophilia through activation of α1‐adrenoceptors. J. Leukoc. Biol. 61: 689‐694; 1997.
The involvement of the sympathetic and dopaminergic systems on blood neutrophilic leucocytosis observed during anaphylaxis was investigated. Blood neutrophil counts impressively increased 1 h after intravenous injection of ovalbumin (OVA, 250 μg/kg) into OVA-immunized rats. The increase in neutrophil counts induced by OVA was abrogated after catecholamine depletion by reserpine. Either adrenalectomy or the α- and β-adrenoceptor antagonists phentolamine and propranolol, respectively, had only minor inhibitory effects on neutrophilia induced by antigen. On the other hand, pretreatment with the dopaminergic antagonists chlorpromazine and pimozide significantly inhibited the neutrophilia. The intravenous injection of apomorphine, a dopaminergic agonist, increased neutrophil counts in naive animals, while chlorpromazine completely inhibited this phenomenon. These results suggest that dopaminergic mechanisms play a role in the systemic neutrophilia observed during anaphylactic shock.
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