Reduction of acute inflammation in rats by diazepam: Role of peripheral benzodiazepine receptors and corticosterone

Carrageenin causes a reproducible inflammatory reaction and remains the sta ndard irritant for examining acute inflammation and anti-inflammatory drugs . High doses of diazepam (10.0-20.0 mg/Kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenin admini stration. The present experiment was undertaken to investigate the possible roles of peripheral-type benzodiazepine receptors (PBRs) and corticosteron e on the anti-inflammatory effects of diazepam. Five experiments were condu cted to assess the effects of a single dose (10.0 mg/Kg) of diazepam on car rageenin-induced paw edema (CIPE), pleurisy and increase in vascular permea bility in rats. Results showed that: 1. diazepam or Ro5-4864 (a PER agonist ) treatment reduced CIPE values; 2. prior treatment with PK11195 (a non-ben zodiazepine PER antagonist) suppressed the effects of either diazepam or Ro 5-4864 on CIPE: 3. diazepam reduced the volume of the pleural exudate in ca rrageenin-injected rats, as well as its leukocyte count: I. diazepam treatm ent reduced the magnitude of the increase in vascular permeability caused b y carrageenin: 5. adrenalectomy suppressed the effects of diazepam on CIPE; and 6. diazepam treatment increased the serum concentration of corticoster one. These results suggest a relevant role of PER and corticosterone on dia zepam-induced changes in inflammation. They are discussed in the light of a possible activation of mitochondrial PBRs within the adrenal gland cells b y diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE.