The alpha2-adrenoceptor antagonist yohimbine reduces glial fibrillary acidic protein upregulation induced by chronic morphine administration.
Previous literature data show prominent interactions between alpha(2)-adrenoceptor ligands and opioid drugs, however, the nature of such interactions is still largely unknown. In the present study, we aimed to examine the potential protective effect of yohimbine, a alpha(2)-adrenoceptor antagonist, against glial fibrillary acidic protein (GFAP) alterations elicited by chronic morphine treatment. Increased astrogliosis, as indicated by increased GFAP immunohistochemical staining, was observed in the ventral tegmental area, nucleus accumbens shell, and frontal cortex of chronic morphine-treated (10 mg kg(-1), i.p., every 12 h for 13 days) rats compared with those treated with saline. Pretreatment with yohimbine (2 mg kg(-1), i.p., 30 min before each morphine injection) provided protection against morphine-induced GFAP upregulation. The present study demonstrates that yohimbine pretreatment reduces long-term morphine exposure-induced alterations in the astroglial reaction, suggesting that alpha(2)-adrenergic mechanisms may play an important role in mediating morphine-induced pathological effects in the brain.
Garrido
Elisa
E
Laboratory of Pharmacology and Toxicology, Facultad de Farmacia, Universidad San Pablo CEU, Boadilla del Monte, Madrid, Spain.
Pérez-García
Carmen
C
Alguacil
Luis F
LF
Díez-Fernández
Carmen
C
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D005904:Glial Fibrillary Acidic Protein; D009294:Narcotics; D015016:Yohimbine; D009020:Morphine