Up-regulation of [3H]DTG but not [3H](+)-pentazocine labeled sigma sites in mouse spinal cord by chronic morphine treatment.
To monitor the possible effect of morphine on sigma sites, binding characteristics of [3H](+)-pentazocine and [3H]1,3-di-(2-tolyl)guanidine (DTG) to brain and spinal cord membranes of morphine-treated and control mice were compared. For morphine treatment, a single injection (100 mg/kg, s.c.) of morphine was followed 4 h later by pellet implantation (75 mg morphine free base). Animals were sacrificed 24, 72 h or 7 days later. The equilibrium dissociation value (Kd) and the density (Bmax) of [3H](+)-pentazocine binding remained unaffected by morphine treatment. Also, no change was found in Kd and Bmax values of [3H]DTG labeled sigma2 subtypes after any morphine treatment schedule when measured in the presence of 100 nM (+)-pentazocine. However, the Bmax of [3H]DTG binding in the spinal cord in the absence of 100 nM (+)-pentazocine, was significantly elevated 72 h after implantation of the morphine pellet and recovered by 7 days, a time when the antinociceptive effect produced by the morphine pellet had dissipated. These data suggest that one population of sigma sites, that has a high affinity for [3H]DTG, but is not equivalent with the [3H](+)-pentozocine labeled sigma1 subtype or the [3H]DTG labeled sigma2 subtype, is upregulated by morphine and, therefore, may play a role in the development of tolerance to or dependence on the effects of morphine.
Kovács
K J
KJ
Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108, USA.
Larson
A A
AA
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004361:Drug Tolerance; D006146:Guanidines / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence; D009294:Narcotics / Q000494:pharmacology; D010423:Pentazocine / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*
D006146:Guanidines; D009294:Narcotics; D017480:Receptors, sigma; D009020:Morphine; C050232:1,3-ditolylguanidine; D010423:Pentazocine