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 bra in serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in ute ro exposure to methamphetamine could result in long-term alterations i n postnatal 5-HT systems. Pregnant Sprague-Dawley rats, administred ei ther saline or (+/-)methamphetamine (5 mg/kg, s.c., b.i.d.) from gesta tional day 13 to 20, were divided into three treatment groups: Saline- injected/Ad Lib Fed (VEH); Saline-injected/Pair Fed (PF); and methamph etamine injected (METH). Prenatal methamphetamine exposure did not alt er litter size, gender number, or progeny birth weights. Functional al terations 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 injectio n of the 5-HT releaser p-chloroamphetamine (PCA; 8 mg/kg). Prenatal me thamphetamine produced long-term marked (-30 to -62%) attenuation of p lasma 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 gen der. No significant differences were observed in the density of cortic al 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 differ ences in cortical 5-HT uptake sites observed between PF and METH treat ed dams 2 days post-parturition indicates that methamphetamine was not neurotoxic to the pregnant dams. These data, which demonstrate longte rm postnatal deficits in 5-HT mediated renin secretion, suggest select ive functional alterations of brain 5-HT systems in male and female pr ogeny exposed in utero to methamphetamine. (c) 1993 Wiley-Liss, Inc.