Effects of high doses of diazepam on carrageenin-induced paw edema in rats.
Benzodiazepine (BDZ) receptor sites play a relevant role in immune/inflammatory reactions. Acute BDZ treatments were shown not only to suppress cell proliferation in rat thymus but also to decrease TNF-alpha, IL-1 and IL-6 release from adult mouse macrophages. In the present investigation the effects of acute (10.0 and 20.0 mg/kg) and long-term (10.0 mg kg-1 day-1, for 21 days) diazepam treatment on carrageenin-induced paw edema were studied in rats. The results showed that acute treatment with high doses of diazepam decreased paw edema volume in a dose-dependent manner, and this effect was observed as early as 1 h after the administration of the 20.0 mg/kg dose and continued until the last measurement was performed (8 h). In contrast, long-term diazepam administration did not modify the phlogistic-induced edema. Taken together, these data show that 1) acute diazepam treatment with high doses decreases the volume of the acute inflammatory paw edema developed by the organism as a response to carrageenin-induced injury, and 2) long-term diazepam treatment induces tolerance to this effect. These results are discussed in the light of a possible effect of diazepam on the components of the rat cellular and humoral immune/inflammatory reaction such as T lymphocytes and/or interleukins.
Lazzarini
R
R
Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Brasil.
Paulino
C A
CA
Malucelli
B E
BE
Palermo-Neto
J
J
D000818:Animals; D002351:Carrageenan; D003975:Diazepam / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005121:Extremities; D018757:GABA Modulators / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects
D018757:GABA Modulators; D011963:Receptors, GABA-A; D002351:Carrageenan; D003975:Diazepam