Decreased noradrenergic and serotonergic reactivity of vas deferens of newborn rats from mothers treated with the serotonin reuptake inhibitor fluoxetine during pregnancy and breast-feeding Janaina D. Pereira, Afonso Caricati-Neto, Aron Jurkiewicz ⁎ , Neide H. Jurkiewicz Department of Pharmacology, Federal University of São Paulo (Unifesp), Rua 3 de maio 100, 04044-020, São Paulo-SP, Brazil Received 12 June 2007; accepted 10 September 2007 Abstract Female Wistar rats were treated with the serotonin reuptake inhibitor fluoxetine (10 mg/kg/i.p/day), during pregnancy and breast-feeding, for the study of the corresponding newborn rats. At the end of the preweaning period, the 30-day old litters had their vas deferens removed for testing peripheral sympathetic reactivity, through the following experiments in vitro: (a) concentration–contraction curves for serotonin and for the adrenergic agonists noradrenaline, phenylephrine, clonidine and dopamine or for the indirect agonist tyramine (b) contractions induced by electric field stimulation, as an indicator of sympathetic neurotransmission (c) release of endogenous noradrenaline, measured by real-time determinations on HPLC (d) Ca +2 time–contraction curves, to check for changes on Ca +2 translocation. Our results showed that the affinity (pD 2 ) for serotonin was strikingly decreased by about 1.5 log units. The pD 2 for adrenergic agonists was decreased by about 0.5 log units, except for dopamine and clonidine. The maximum effects and intrinsic activity were decreased only for dopamine. On the other hand, the response to Ca +2 and the release of noradrenaline from nerve terminals were not modified. In additional experiments, the mother's body weights were measured, showing a decrease during gestation and a recovery during lactation while the offspring's weights were lower than controls. It is concluded that, besides the alterations on body weights, changes on noradrenergic and serotonergic mechanisms were observed and persisted in the newborn, at least one month after parturition. © 2007 Elsevier Inc. All rights reserved. Keywords: Fluoxetine; Serotonin; Neurotransmission; Vas deferens; Pregnancy; Breast-feeding Introduction The main objective of the present work is to evaluate the possibility that peripheral noradrenergic and serotonergic trans- missions are changed in newborn rats of mothers continuously treated with fluoxetine during gestation and preweaning stages. Fluoxetine, an antidepressant drug widely used (Wong et al., 2005), has been described as a selective serotonin reuptake inhibitor (SSRI). It has been frequently prescribed during pregnancy and breast-feeding, and can be detected in plasma of newborn (Weissman et al., 2004) and in human milk (Yoshida et al., 1998). Therefore, it would be desirable to know what kind of consequences for the newborn can result from this long-term treatment. Evidence has already been presented (Vorhees et al., 1994) for potential adverse effects in human neonates exposed in utero to SSRIs (Moses-Kolko et al., 2005), added to a neonatal withdrawal syndrome (Zajecka et al., 1997; Sanz et al., 2005; Anbu and Theodore, 2006, Levinson-Castiel et al., 2006). It is also known that besides blocking serotonin uptake, a number of peripheral effects, such as a potentiation of contractions induced by noradrenaline (Busch et al., 1999, 2000), added to an interference on Ca +2 -dependent effects in smooth muscle (Pullar and Findlay, 1992; Stauderman et al., 1992; Pacher et al., 1999; Mousavizadeh et al., 2002) have been described for fluoxetine. Available online at www.sciencedirect.com Life Sciences 81 (2007) 1501 – 1508 www.elsevier.com/locate/lifescie ⁎ Corresponding author. Tel./fax: +55 11 5576 4569. E-mail address: Aron.farm@epm.br (A. Jurkiewicz). 0024-3205/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2007.09.012