Implication of nociceptin in alterations in cerebral blood flow regulation following postnatal exposure to ethanol in rats

Abstract

This study aimed to investigate whether nociceptin is implicated in the alterations in cerebral blood flow regulation following postnatal exposure to ethanol in Sprague-Dawley rats. Animals received ethanol (2.5 g/kg, s.c.) twice a day, 2 hours apart, on postnatal 6, 7 and 8 days. The changes in regional cerebral blood flow (rCBF) in response to the changes in mean arterial blood pressure were determined at 4-, 8-, and 12-weeks of age by laser-Doppler flowmetry. Hypotension was induced by the gradual withdrawal of blood from arterial catheter, and the reversal of blood pressure was produced by the reinfusion of blood. Expression of nociceptin-like immunoreactivity was determined in dura mater and cerebral cortex using immunohistochemistry. Postnatal exposure to ethanol almost abolished the autoregulation of rCBF in all age groups. Pretreatment with nociceptin (0.138 g/kg, i.p.) but not with [Nphe1]nociceptin(1-13)NH2 (1.38 g/kg, i.p.), a selective competitive nociceptin receptor antagonist, 5 minutes prior to ethanol administration preserved the autoregulation of rCBF in all age groups. Postnatal exposure to ethanol markedly increased the expression of nociceptin-like immunoreactivity in dura mater, which was significantly inhibited by pretreatment with 7-nitroindazole monosodium salt (7-NINA, 50 mg/kg, i.p.) as well as aminoguanidine (1 mg/kg, i.p.) 5 minutes prior to ethanol administration in all age groups. Postnatal exposure to ethanol markedly increased the expression of nociceptin-like immunoreactivity in cerebral cortex, which was significantly inhibited by pretreatment with 7-NINA as well as aminoguanidine 5 minutes prior to ethanol administration in all age groups. The values of arterial blood gas analysis were not significantly different from the basal levels in all groups. These results suggest that nociceptin is deeply implicated in the compensatory mechanisms for the nitric oxide-dependent alterations in CBF autoregulation following postnatal exposure to ethanol.