Maternal fluoxetine treatment decreases behavioral response to dopaminergic drugs in female pups

Abstract

Since serotonin (5-HT) acts as neurotrophic factor, the use of fluoxetine (FLX) by mothers during pregnancy and/or lactation could disrupt brain development of the progeny. To unveil if maternal FLX exposure could compromise the functional integrity of monoaminergic and GABA-ergic neurotransmission, the behavioral responses of male and female mouse pups to diethylpropion, apomorphine, 8-OH-DPAT and diazepam were evaluated. Swiss dams were gavaged daily with FLX (7.5 mg/kg) or tap water during pregnancy day zero to weaning (postnatal day 21). Pups were evaluated on postnatal day 40. The behavioral response to diethylpropion was assessed in the open-field and drug-induced stereotyped behavior; to apomorphine in the drug-induced stereotyped behavior; to diazepam, in the elevated plus maze test and to 8-OH-DPAT in the open-field and forced swimming tests. Exposure to FLX did not influence any drug-induced behavioral response in males. Conversely, in females, FLX exposure significantly prevented diethylpropion-induced hyperactivity in the open-field and reduced stereotyped behavior induced by diethylpropion and apomorphine. In conclusion, the results showed that maternal exposure to FLX induced in female pups long-lasting decreased dopaminergic-mediated behaviors, suggesting altered development of the dopaminergic system. If this alteration also occurs in humans, female children of women who use FLX during pregnancy and lactation may express dopaminergic behavioral alterations and/or altered responsiveness to psychotropic medications later in life.