Prenatal morphine exposure differentially alters TH-immunoreactivity in the stress-sensitive brain circuitry of adult male and female rats

Previously, we demonstrated that exposure to morphine during gestation incr eases hypothalamic norepinephrine (NE) content and turnover rate in adult m ale rats and decreases these measures in adult females. To investigate the basis of these alterations, the present study examined the effects of prena tal exposure to morphine on tyrosine hydroxylase immunoreactivity (TH-IR) i n the brains of adult male and female progeny. In male rats, prenatal morph ine exposure significantly increased the density of TH-IR in cells and fibe rs in the caudal paraventricular nucleus of the hypothalamus (PVN) and locu s coeruleus (LC), but had no effects in the lateral hypothalamus (LH), In f emale rats that were ovariectomized (OVX), prenatal morphine exposure signi ficantly decreased the density of TH-IR in cells and fibers in the LC, Inte restingly, an injection of estrogen in OVX control females reduced the mean optical density of TH-IR in the LC, but it was ineffective in drug-exposed females in the same brain region, Estrogen injections also reduced the mea n optical density of TH-IR in the LH but not in the PVN of females, regardl ess of prenatal drug exposure. Thus, the present study suggests that prenat al morphine exposure induces long-term, sex-specific alterations in TH-IR i n the PVN and LC of adult progeny. (C) 2000 Elsevier Science Inc.