title: Effects of different doses and schedules of diazepam treatment on lymphocyte parameters in rats.
abstract: Benzodiazepines (BZD) are widely used for the treatment of anxiety. They enhance GABA-ergic neurotransmission through the binding on specific BDZ recognition sites, within the GABA(A) receptor-ion channel complex. However, recent studies showed that BZD also act on peripheral benzodiazepine receptor sites (PBR) or translocator protein 18 kDa (TSPO). Evidence for a direct immunomodulatory action for BZD emerged from studies that demonstrated the presence of TSPO on immune/inflammatory cells. The present study was designed to analyze the effects of diazepam on rat lymphocyte parameters, specifically on phenotype, cell proliferation and cell death. The effects of both acute and long-term (21 days) diazepam (1 and 10 mg/kg/day) administrations were evaluated. Results showed that diazepam (1 mg/kg) treatment did not change the immune parameters analyzed. However, both diazepam (10 mg/kg) acute and long-term treatments decreased the number of apoptotic cells; they also increased the percentage of T cytotoxic cells; decreased the percentage of B cells and increased the corticosterone serum levels. The induction of functional tolerance was suggested for the highest dose of diazepam (10 mg/kg), but not for the smaller dose (1 mg/kg) used, at least for diazepam effects on corticosterone serum levels. Diazepam effects were discussed as being related to the number of TSPO sites present on immune cells and/or to the increased levels of serum corticosterone observed after the treatments used.
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Camila Bento
authors.initials: CB
authors.lastname: de Lima
authors.forename: Monica
authors.initials: M
authors.lastname: Sakai
authors.forename: Andreia Oliveira
authors.initials: AO
authors.lastname: Latorre
authors.forename: Regina Lucia de Moraes
authors.initials: RL
authors.lastname: Moreau
authors.forename: João
authors.initials: J
authors.lastname: Palermo-Neto
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000097:blood; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D003345:Corticosterone / Q000097:blood / Q000276:immunology; D003975:Diazepam / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
chemical_list: D014151:Anti-Anxiety Agents; D002352:Carrier Proteins; D007155:Immunologic Factors; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D003975:Diazepam; D003345:Corticosterone