Inhibitory effects of alprazolam on the development of acute experimental autoimmune encephalomyelitis in stressed rats.
The progression and development of multiple sclerosis (MS) has long been hypothesized to be associated with stress. Benzodiazepines have been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on their effects on MS, or experimental autoimmune encephalomyelitis (EAE), a model for human MS. We designed experiments conducted to ascertain whether alprazolam could modify the clinical, histological and neuroendocrine manifestations of acute EAE in Lewis rats exposed to a chronic auditory stressor. EAE was induced by injection of an emulsion of MBP and complete Freund's adjuvant containing Mycobacterium tuberculosis H37Ra. Stress application and treatment with drugs (placebo or alprazolam) were initiated 5days before inoculation and continued daily for the duration of the experiment (days 14 or 34 postinoculation).Our results show significant increases in the severity of neurological signs, the histological lesions of the spinal cord (inflammation), and the corticosterone plasmatic levels in stressed rats compared to those non-stressed ones. Treatment with alprazolam reversed the adverse effects of stress. These findings could have clinical implications in patients suffering from MS treated with benzodiazepines, so besides the psychopharmacological properties of alprazolam against stress, it has beneficial consequences on EAE.
Núñez-Iglesias
María J
MJ
Lennart Levi Stress and Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine and Nursing, University of Santiago de Compostela,C/San Francisco, s/n.15782 Santiago de Compostela, Spain. snl@usc.es
Novío
Silvia
S
Almeida-Dias
Antonio
A
Freire-Garabal
Manuel
M
D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005620:Freund's Adjuvant; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009622:Noise / Q000009:adverse effects; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology; D013315:Stress, Psychological / Q000150:complications*
D014151:Anti-Anxiety Agents; D005620:Freund's Adjuvant; D003345:Corticosterone; D000525:Alprazolam