Prenatal methamphetamine attenuates serotonin mediated renin secretion in male and female rat progeny: evidence for selective long-term dysfunction of serotonin pathways in brain.

In adult rats, methamphetamine produces biochemical alterations in brain serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to methamphetamine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats, administered either saline or (+/-)methamphetamine (5 mg/kg, s.c., b.i.d.) from gestational day 13 to 20, were divided into three treatment groups: Saline-injected/Ad Lib Fed (VEH); Saline-injected/Pair Fed (PF); and methamphetamine injected (METH). Prenatal methamphetamine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny and in PD 30 female progeny by measuring changes in 5-HT mediated increases in plasma hormones following a single injection of the 5-HT releaser p-chloroamphetamine (PCA; 8 mg/kg). Prenatal methamphetamine produced long-term marked (-30 to -62%) attenuation of plasma renin responses to PCA in male and female progeny. In contrast, no alterations were observed in the ACTH, corticosterone, or prolactin responses to PCA in male and female progeny. Prenatal methamphetamine did not alter basal levels of any hormones measured regardless of gender. No significant differences were observed in the density of cortical or hypothalamic 5-HT uptake sites, or in the density of cortical 5-HT1 or 5-HT2 receptors in male progeny. The lack of significant differences in cortical 5-HT uptake sites observed between PF and METH treated dams 2 days post-parturition indicates that methamphetamine was not neurotoxic to the pregnant dams. These data, which demonstrate longterm postnatal deficits in 5-HT mediated renin secretion, suggest selective functional alterations of brain 5-HT systems in male and female progeny exposed in utero to methamphetamine.