Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy

Abstract

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.

Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond: A review of animal and human studies

“…Similar results have been reported in other studies with rodents [43][44][45][46][47][48][49][50]. In addition to low birth weight due to prenatal SSRIs, da-Silva et al also found a sex and treatment effect, females with SSRI exposure had lower birth weight than males and nonexposed females [47].…”

Effects of fluoxetine and imipramine in rat fetuses treated during a critical gestational period: a macro and microscopic study

“…9 In humans, the teratogenic potential of most therapeutic agents remains unknown and is rarely related to specific malformations. It is estimated that 10% of congenital malformations are attributed to environmental causes, including the use of medication, while 21% occur due to either genetic or chromosomal abnormalities.…”

“…The rats were then separated into three groups (n = 5 each) and treated intraperitoneally with 10mg/kg/ day 7 of the test substances on the ninth, tenth and eleventh day The administration of 10mg/kg/day is equivalent to the dose used for treating anxiety-related disorders, 7 although other studies have reported that fluoxetine has been prescribed at doses ranging from 8mg to 16mg/kg/day. 9 On the twenty-first day of pregnancy, the rats were weighed and anesthetized intraperitoneally with xilazine (Rompum® 20mg/ mL, Bayer) and ketamine hydrochloride (Ketamin-S(+)® 50mg/ mL, Cristália) at a ratio of 1:3 at a dose of 0.3mL for each 100g of animal weight. Through a long abdominal incision, the fetuses were exposed and distributed into 3 groups: 55 in the control group, 62 in the fluoxetine group and 57 in the imipramine hydrochloride group.…”

Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects

“…Few investigations have also focused on the behavioral consequences of perinatal treatment with the novel antidepressants, such as venlafaxine, mirtazapine, reboxetine, nefazodone, and milnacipran. A recent report found no detrimental effects in rats gestationally exposed to venlafaxine (da Silva et al, 1999). There are no published reports showing neurochemical and behavioral effects induced by perinatal administration of novel antidepressants.…”