Up-regulation of [³H]DTG but not [³H](+)-pentazocine labeled σ sites in mouse spinal cord by chronic morphine treatment

To monitor the possible effect of morphine on σ sites, binding characteristics of [³H](+)-pentazocine and [³H]l,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 (K(d)) and the density (B(max)) of [³H](+)-pentazocine binding remained unaffected by morphine treatment. Also, no change was found in K(d) and B(max) values of [³H]DTG labeled σ₂ subtypes after any morphine treatment schedule when measured in the presence of 100 nM (+)- pentazocine. However, the B(max) 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 σ sites, that has a high affinity for [³H]DTG, but is not equivalent with the [³H](+)-pentozocine labeled σ₁ subtype or the [³H]DTG labeled σ₂ subtype, is upregulated by morphine and, therefore, may play a role in the development of tolerance to or dependence on the effects of morphine.