Mifepristone (RU486) inhibits lateral perforant path long-term potentiation in hippocampal slices from prenatally morphine-exposed female rats

Abstract

In brain slices from prenatally saline-exposed female rats during proestrus and diestrus, long-term potentiation (LTP) can be induced in the lateral perforant pathway (LPP). Prenatal morphine exposure suppresses LTP induction in the LPP during proestrus. Here we studied synaptic plasticity in the LPP in slices from female rats prenatally exposed to morphine. Two additional factors were investigated: the role of the estrous cycle and role of glucocorticoid receptors. Hippocampal slices were prepared from adult, prenatally saline- or morphine-exposed female rats. One hour prior to decapitation, vaginal smears were obtained and the rats either in proestrus or diestrus were treated with a non-specific glucocorticoid receptor antagonist mifepristone (RU486) or with a vehicle. LPP was stimulated with high-frequency stimulation. Short-tem plasticity (STP) and the induction and maintenance of long-term potentiation (LTP) were assessed. In all groups of prenatally saline-exposed rats, LTP was induced and maintained with the exception of RU486-treated rats during proestrus where the LTP was induced but not maintained. In prenatally morphine-exposed females in diestrus, both STP and LTP were induced after postnatal vehicle treatment. In morphine-exposed, proestrous females, neither STP nor LTP were induced irrespective of the postnatal treatment. Thus, prenatal morphine exposure suppresses the induction of LTP in the LPP, except during diestrus.Data indicate that the induction and maintenance of LTP in the LPP in hippocampal slices from female rats is multifactorial: ovarian steroids and functionality of glucocorticoid receptors cooperation are necessary for induction and maintenance of the LTP, prenatal morphine exposure interferes with this process possibly by it's long-term effects on synaptic plasticity.