Cognitive, Behavioral, and Systems NeuroscienceResearch PaperProlactin reduces the damaging effects of excitotoxicity in the dorsal hippocampus of the female rat independently of ovarian hormones

We reported previously that lactation prevents the cell damage induced by kainic acid (KA) excitotoxicity in the CA1, CA3, and CA4 areas of the dorsal hippocampus compared to rats in diestrus phase, and hypothesize that pronounced fluctuations of hormones, such as ovarian steroids and prolactin (PRL), have a role in the neuroprotection of the dorsal hippocampus during lactation. PRL is thought to be involved in modulating neural excitability and seizure activity. To investigate actions of prolactin that minimize KA-induced cell damage in the hippocampus, female intact and ovariectomized (OVX) rats were treated for 4 days with a daily dose of 100 μg of prolactin or vehicle. On the third day of prolactin treatment, rats received a systemic dose of 7.5 mg/kg of KA and were sacrificed 48 h later. Immunostaining for Neu-N revealed a significant decrease in cell number in the CA1, CA3 and CA4 areas of intact or OVX, vehicle-treated rats after KA, whereas prolactin treatment prevented cell loss in the CA3 area of intact, and in the CA1, CA3, and CA4 of OVX rats. Fluoro-Jade C staining confirmed these observations. Kainate-induced seizure behavior progressed further in OVX rats, but was attenuated in prolactin-treated rats, both intact and OVX, compared to vehicle-treated rats. These data indicate that prolactin diminishes the damaging actions of excitotoxicity in the kainate model of epilepsy.