Transient down-regulation of neonatal rat brain mu-opioid receptors upon in utero exposure to buprenorphine

Abstract

Gestational actions of the mixed agonist-antagonist buprenorphine on mu- and kappa 1-opioid binding in neonatal and maternal rat brain were investigated. Upon exposure of pregnant rats to 0.5 mg/kg buprenorphine for 7 days prior to birth, postnatal day-one (P1) and P7 offspring brain mu-binding parameters (Kd and Bmax) were assessed with 3H-labeled [D-Ala2,Mephe4,Gly-ol5] enkephalin (DAMAGE). DAMAGE binding was attenuated by 64% in P1 membranes, whereas P7 preparations showed no changes. The same buprenorphine regimen resulted in diminished DAMGE Bmax values in mothers' brains, 2 but not 7 days after cessation of drug administration. Receptor density changes were not accompanied by alteration of mu-binding affinities. Although the postnatal developmental profile of kappa 1 opioid receptors in rat brain measured with [3H]U69593 revealed the presence of an ample number of sites for detection, their binding parameters in P1, P7 pups and mothers were unaffected by 0.5 mg/kg buprenorphine. In summary, buprenorphine administration to pregnant rats transiently down-regulates mu opioid receptors in neonatal and maternal brain.