Titre du document / Document title

Involvement of diazepam-insensitive benzodiazepine receptors in the suppression of DOI-induced head-twitch responses in diabetic mice

Auteur(s) / Author(s)

MIYATA Shigeo ⁽¹⁾ ; HIRANO Shoko ⁽¹⁾ ; KAMEI Junzo ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, JAPON

Résumé / Abstract

Rationale: We previously reported that the head-twitch responses induced by the 5-HT₂ receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) (DOI-HTRs) were decreased in streptozotocin-induced diabetic mice. Objectives: We examined the involvement of γ-aminobutyric acid (GABA)/benzodiazepine system on the suppression of DOI-HTRs in diabetic mice. Results: The benzodiazepine receptor antagonist flumazenil (0.1-1 mg/kg, i.v.) dose-dependently and significantly increased DOI-HTRs in diabetic mice to the same levels as in nondiabetic mice. However, flumazenil (0.11 mg/kg, i.v.) did not affect DOI-HTRs in nondiabetic mice. The benzodiazepine receptor agonist diazepam (0. I1 mg/kg, i.p.) had no effect on DOI-HTRs in either nondiabetic or diabetic mice. The GABA_A receptor antagonist bicuculline (0.1-1 mg/kg, i.p.) and the benzodiazepine receptor partial inverse agonist Ro 15-4513 (0.1-1 mg/kg, i.v.) dose-dependently and significantly suppressed DOI-HTRs in nondiabetic mice to the same levels as in diabetic mice. Ro 15-4513-induced reduction of DOI-HTRs in nondiabetic mice was completely antagonized by flumazenil (1 mg/kg, i.v.), but not diazepam (0.3 mg/kg, i.p.). Conclusions: We suggest that the abnormal diazepam-insensitive benzodiazepine receptor function partly underlies the suppression of DOI-HTRs in diabetic mice.

Revue / Journal Title

Psychopharmacologia   ISSN 0033-3158   CODEN PSYPAG 

Source / Source

2006, vol. 186, n^o1, pp. 1-6 [6 page(s) (article)] (1 p.1/4)

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1959) (Revue)

Mots-clés anglais / English Keywords

Benzodiazepine antagonist ; Endocrinopathy ; Benzodiazepine derivatives ; Vertebrata ; Mammalia ; Rodentia ; Hypnotic ; Anticonvulsant ; Psychotropic ; 5-HT2A serotonin receptor ; Flumazenil ; Mouse ; Animal ; Diabetes mellitus ; Benzodiazepine receptor ; Tranquillizer ; Diazepam ; Mechanism of action ;

Mots-clés français / French Keywords

Antagoniste benzodiazépine ; Endocrinopathie ; Benzodiazépine dérivé ; Vertebrata ; Mammalia ; Rodentia ; Hypnotique ; Anticonvulsivant ; Psychotrope ; Récepteur sérotoninergique 5-HT2A ; Flumazénil ; Souris ; Animal ; Diabète ; Récepteur benzodiazépinique ; Tranquillisant ; Diazépam ; Mécanisme action ;

Mots-clés espagnols / Spanish Keywords

Antagonista benzodiazepina ; Endocrinopatía ; Benzodiazepina derivado ; Vertebrata ; Mammalia ; Rodentia ; Hipnótico ; Anticonvulsivante ; Psicotropo ; Receptor serotoninérgico 5-HT2A ; Flumazenilo ; Ratón ; Animal ; Diabetes ; Receptor benzodiazepínico ; Tranquilizante ; Diazepam ; Mecanismo acción ;

Mots-clés d'auteur / Author Keywords

Benzodiazepine receptor ; Diabetes ; Diazepam ; Diazepam-insensitive sites ; DOI ; Flumazenil ; Head-twitch ; Ro 15-4513 ; 5-HT2A receptor ;

Localisation / Location

INIST-CNRS, Cote INIST : 1761, 35400014266440.0010