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.
Subject(s)
Behavior, Animal/drug effects , Dopamine Agents/pharmacology , Fluoxetine/pharmacology , Maternal Exposure , Selective Serotonin Reuptake Inhibitors/pharmacology , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Age Factors , Analysis of Variance , Animals , Apomorphine/pharmacology , Body Weight/drug effects , Exploratory Behavior/drug effects , Female , Locomotion/drug effects , Male , Mice , Pregnancy , Pyrrolidines/pharmacology , Serotonin Receptor Agonists/pharmacology , Sex Factors , Stereotyped Behavior/drug effects , Swimming , Time FactorsABSTRACT
BACKGROUND/AIMS: Fluoxetine (FLX) has been widely prescribed for depression during pregnancy and/or lactation. Since serotonin is a neurotrophic factor, the use of FLX by mothers could disrupt brain development resulting in behavioral alterations in their progeny. This study evaluated the effects of developmental FLX exposure on anxiety, depression, aggressivity and pain sensitivity of male and female mice pups. METHODS: Swiss dams were treated daily, by gavage, with 7.5 mg/kg of FLX during pregnancy and lactation. Pups were submitted to open-field, forced swimming, elevated plus-maze, intruder-resident and hot plate tests at adolescence and adulthood. RESULTS AND CONCLUSION: In male pups, exposure to FLX decreased ambulation at postnatal day (PND) 40 and tended (p=0.07) to increase the latency to the first attack in the intruder-resident test at PND 70, suggesting decreased impulsivity. In female pups, FLX exposure increased immobility time in the forced swimming test at both PND 30 and 70, which is interpreted as depressive-like behavior. In conclusion, our results suggest that maternal exposure to FLX during pregnancy and lactation results in enduring behavioral alterations in male and female pups throughout life.
