title: Socio-psychological stress-induced antinociception in diabetic mice.
abstract: BACKGROUND
  Although it is well established that different forms of stress produce a pronounced antinociception, the effect of diabetes on psychological stress-induced antinociception is not yet clear.
  
  
  OBJECTIVE
  The effect of diabetes on psychological stress-induced antinociceptive effect was assessed in mice.
  
  
  METHODS
  Animals were rendered diabetic by an injection of streptozotocin (200 mg/kg, i.v.). Mice were exposed to psychological stress in the compartment of a communication box. The antinociceptive response was evaluated by the tail-flick test, using radiant heat as a stimulus, which was performed before stress (pre-stress latency) and 0, 30 and 60 min after stress.
  
  
  RESULTS
  Exposure to socio-psychological stress for 5, 10 and 15 min produced duration-dependent antinociception in diabetic mice. However, in non-diabetic mice, no appreciable antinociception was found even in the case of socio-psychological stress for 15 min. Pretreatment with diazepam (0.3 mg/kg, i.p.) significantly attenuated socio-psychological stress-induced antinociception in diabetic mice (vehicle: 62.9 +/- 5.5%, n = 10; diazepam: 22 +/- 1%, n = 10). Furthermore, pretreatment with flumazenil (1 mg/kg, i.v.), a benzodiazepine receptor antagonist, also significantly reduced socio-psychological stress-induced antinociception in diabetic mice (vehicle: 77.9 +/- 5.0%, n = 10; flumazenil: 5.8 +/- 1.2%, n = 10). In contrast, pretreatment with methyl beta-carboline-3-carboxylate (beta-CCM, 2 mg/kg, i.v.), a benzodiazepine receptor inverse agonist, significantly enhanced socio-psychological stress-induced antinociception in non-diabetic mice (vehicle: 4.9 +/- 0.6%, n = 10; beta-CCM: 61.5 +/- 5.9%, n = 10), but not in diabetic mice (vehicle: 50.7 +/- 4.5%, n = 10; beta-CCM: 64.4 +/- 7.2%, n = 10).
  
  
  CONCLUSIONS
  These results indicate that emotional stress can readily induce antinociception in diabetic mice. Furthermore, this enhanced emotional stress-induced antinociception might be attributable to an increase in the production and/or release of endogenous ligands for benzodiazepine receptors, such as diazepam binding inhibitor, which act as inverse benzodiazepine receptor agonists.
authors.affiliation: Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. kamei@hoshi.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Kamei
authors.forename: M
authors.initials: M
authors.lastname: Ohsawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D000927:Anticonvulsants / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000523:psychology*; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects / Q000523:psychology*; D013311:Streptozocin; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology*
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D002243:Carbolines; D003292:Convulsants; D018757:GABA Modulators; D005442:Flumazenil; D013311:Streptozocin; C036150:beta-carboline-3-carboxylic acid methyl ester; D003975:Diazepam