Cellular adaptation to opiates alters ion-channel mRNA levels.
The chronic use of several drugs, including opiates, results in the stereotypical behaviors characteristic of addiction. Alterations in gene expression have been associated with the use of these addictive drugs. Previous studies, however, have been limited to describing changes in amounts of individual mRNAs from single tissue samples. Cellular adaptation to opiates, reflected in the regulation of the expression of many different mRNAs, seems likely to contribute to the complicated behaviors of addiction. The present studies examined coordinate alterations in the amounts of multiple mRNAs in the rat striatum and in NG108-15 cells after opioid stimulation or the precipitated withdrawal of opioid use. The experimental approach combined amplification of the poly(A)+ RNA population with reverse Northern blot analysis to simultaneously characterize the relative changes in several mRNAs. Morphine treatment of rats for 5 days was associated with a reduction in the amount of striatal RNA for the voltage-sensitive K+ channel without significant changes in other ion channels. In NG108-15 cells stimulation with the delta-opiate receptor agonist [D-Ala2,D-Leu5]enkephalin (DADLE) alone and followed by naloxone (precipitated withdrawal) caused relative changes in the abundances of several mRNAs. The composite effects of alterations in the abundance of multiple mRNAs (and the proteins they encode) in response to opioid use likely contribute to the development and maintenance of opiate-mediated behaviors.
Mackler
S A
SA
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Eberwine
J H
JH
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000235:genetics
D007473:Ion Channels; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D019204:GTP-Binding Proteins