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

• Published in: European journal of pharmacology 1998-05, Vol.350 (1), p.47-52
• Main Authors: Kovács, Katalin J, Larson, Alice A
• Format: Article
• Language: English
• Subjects: (+)-Pentazocine; Analgesics; Analysis of Variance; Animals; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Drug Tolerance; DTG (1,3-di-(2-tolyl)guanidine); G receptor binding; Guanidines - metabolism; Male; Medical sciences; Mice; Morphine - pharmacology; Morphine Dependence; Morphine tolerance; Narcotics - pharmacology; Neuropharmacology; Pentazocine - metabolism; Pharmacology. Drug treatments; Receptors, sigma - metabolism; Spinal Cord - drug effects; Spinal Cord - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00220-9

To monitor the possible effect of morphine on σ sites, binding characteristics of [ 3 H] (+)-pentazocine and [ 3 H] 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 ( K d) and the density ( B max) of [ 3 H] (+)-pentazocine binding remained unaffected by morphine treatment. Also, no change was found in K d and B max values of [ 3 H] DTG labeled σ 2 subtypes after any morphine treatment schedule when measured in the presence of 100 nM (+)-pentazocine. However, the B max of [ 3 H] 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 [ 3 H] DTG, but is not equivalent with the [ 3 H] (+)-pentozocine labeled σ 1 subtype or the [ 3 H] DTG labeled σ 2 subtype, is upregulated by morphine and, therefore, may play a role in the development of tolerance to or dependence on the effects of morphine.