title: Morphine-induced opioid receptor down-regulation detected in intact adult rat brain cells.
abstract: Intact brain cells dissociated from the brains of adult rats were used to study the regulation of opioid receptors by in vivo chronic morphine treatment. When the specific binding of [3H]naloxone in a physiological iso-osmotic buffer was compared in cells obtained from sham-operated rats and in those treated for 6 days with four (2 X 2) 75 mg morphine pellets, it was found that morphine treatment resulted in a significant reduction in the density of [3H]naloxone binding sites. This receptor down-regulation was not accompanied by a change in the receptor affinity for the ligand. This effect of morphine was reversed upon the removal of morphine pellets for 18 h after tolerance induction. When similar experiments were performed using brain homogenates prepared and assayed in the same physiological buffer, there was an increase in the number of [3H]naloxone binding sites in morphine-treated animals compared to controls. On the other hand, when the binding experiments were conducted in 50 mM Tris-HCl buffer, no difference in ligand binding was apparent between control and morphine-treated groups. The present results demonstrate opioid receptor down-regulation by chronic morphine treatment measured in intact brain cells, and suggest that different conclusions may be reached when other tissue preparations are used to assess the receptor density.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects
chemical_list: D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine