Prenatal morphine exposure suppresses mineralocorticoid receptor-dependent basal synaptic transmission and synaptic plasticity in the lateral perforant path in adult male rats.

The effects of prenatal morphine exposure (E11-18) on mineralocorticoid receptor (MR) modulation of synaptic plasticity were investigated in the lateral perforant path (LPP)-dentate gyrus granule cell synaptic system. Hippocampal slices were prepared from adult, prenatally saline- or morphine-exposed male rats. One hour prior to decapitation, some adult male rats were injected subcutaneously with saline or the MR antagonist, canrenoic acid (50 mg/kg). LPP was stimulated with high-frequency (2x100 Hz/0.5 s) and short-term plasticity (STP) and long-term potentiation (LTP) were evaluated at 5 and 30 min poststimulation, respectively. Prenatally saline-exposed male rats injected with saline 1 h prior to decapitation showed significantly higher levels of baseline, STP, and LTP than prenatally saline-exposed, canrenoic acid-treated males. In contrast, prenatally morphine-exposed male rats regardless of saline or canrenoic acid injection 1 h prior to decapitation were comparable in their baseline, STP, and LTP activities. Thus, the results demonstrate that canrenoic acid decreases the efficacy of the basal synaptic transmission in the LPP as well as suppresses synaptic plasticity in saline-exposed males. However, in adult morphine-exposed male rats, canrenoic acid has no other or further effects than a saline treatment suggesting that prenatal morphine exposure suppresses MR-dependent basal synaptic transmission as well as synaptic plasticity.