Naloxone-precipitated withdrawal in morphine-dependent rats increases the expression of alpha 2a-adrenoceptor mRNA in brain.
Opiate withdrawal has been associated with up-regulation of alpha 2-adrenoceptors (mainly the alpha 2A-subtype) in brain. The modulation of these inhibitory receptors regulating norepinephrine release appears to be a relevant mechanism by which the opiate abstinence syndrome might be counteracted. The aim of this study was to investigate possible changes in alpha 2a-adrenoceptor gene expression as the molecular mechanism underlying the opiate withdrawal-induced up-regulation of alpha 2A-adrenoceptors. In morphine-dependent rats (10-100 mg/kg for 5 days), naloxone (2 mg/kg)-precipitated withdrawal induced a rapid (2 h) and marked up-regulation (111%, P < 0.001) in the expression of alpha 2a-adrenoceptor mRNA (Northern and dot-blot analyses) in the cerebral cortex. Acute and chronic morphine treatments did not alter significantly the expression of cortical alpha 2a-adrenoceptor mRNA. The results indicate that the opiate abstinence syndrome is associated with a transcriptional activation of the alpha 2a-adrenoceptor mRNA which can explain the up-regulation of brain alpha 2A-adrenoceptors during opiate withdrawal.
Busquets
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Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain.
Ventayol
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P
García-Sevilla
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JA
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis*; D013375:Substance Withdrawal Syndrome; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D009270:Naloxone; D009020:Morphine