CELLULAR ADAPTATION TO OPIATES ALTERS ION-CHANNEL MESSENGER-RNA LEVELS

The chronic use of several drugs, including opiates, results in the st ereotypical 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 i n amounts of individual mRNAs from single tissue samples. Cellular ada ptation to opiates, reflected in the regulation of the expression of m any different mRNAs, seems likely to contribute to the complicated beh aviors of addiction. The present studies examined coordinate alteratio ns in the amounts of multiple mRNAs in the rat striatum and in NG108-1 5 cells after opioid stimulation or the precipitated withdrawal of opi oid use. The experimental approach combined amplification of the poly( A)+ RNA population with reverse Northern blot analysis to simultaneous ly characterize the relative changes in several mRNAs. Morphine treatm ent of rats for 5 days was associated with a reduction in the amount o f striatal RNA for the voltage-sensitive K+ channel without significan t changes in other ion channels. In NG108-15 cells stimulation with th e delta-opiate receptor agonist [D-Ala2,D-Leu5]enkephalin (DADLE) alon e and followed by naloxone (precipitated withdrawal) caused relative c hanges in the abundances of several mRNAs. The composite effects of al terations in the abundance of multiple mRNAs (and the proteins they en code) in response to opioid use likely contribute to the development a nd maintenance of opiate-mediated behaviors.