UP-REGULATION OF [H-3]DTG BUT NOT [H-3](-PENTAZOCINE LABELED SIGMA-SITE IN MOUSE SPINAL-CORD BY CHRONIC MORPHINE TREATMENT())

To monitor the possible effect of morphine on sigma sites, binding cha racteristics of [H-3](+)-pentazocine and [H-3]1,3-di-(2-tolyl)guanidin e (DTG) to brain and spinal cord membranes of morphine-treated and con trol mice were compared. For morphine treatment, a single injection (1 00 mg/kg, s.c.) of morphine was followed 4 h later by pellet implantat ion (75 mg morphine free base). Animals were sacrificed 24, 72 h or 7 days later. The equilibrium dissociation value (K-d) and the density ( B-max) of [H-3](+)-pentazocine binding remained unaffected by morphine treatment. Also, no change was found in K-d and B-max values of [H-3] DTG labeled sigma(2) subtypes after any morphine treatment schedule wh en measured in the presence of 100 nM (+)-pentazocine. However, the B- max of [H-3]DTG binding in the spinal cord in the absence of 100 nM ()-pentazocine, was significantly elevated 72 h after implantation of t he morphine pellet and recovered by 7 days, a time when the antinocice ptive effect produced by the morphine pellet had dissipated. These dat a suggest that one population of sigma sites, that has a high affinity for [H-3]DTG, but is not equivalent with the [H-3](+)-pentozocine lab eled sigma(1) subtype or the [H-3]DTG labeled sigma(2) subtype, is upr egulated by morphine and, therefore, may play a role in the developmen t of tolerance to or dependence on the effects of morphine. (C) 1998 E lsevier Science B.V. All rights reserved.