Opiate withdrawal induces Narp in the extended amygdala.
The negative affective states associated with drug withdrawal produce long-lasting behavioral effects thought to play a central role in the development and maintenance of dependence. However, little is known about the molecular mechanisms mediating the long-term effects of drug withdrawal. Neuronal activity-regulated pentraxin (Narp) is a secreted neuronal immediate early gene (IEG) product that regulates AMPA receptor clustering at synapses. As both IEGs and changes in AMPA receptor trafficking mediate enduring forms of neuronal plasticity, we have assessed whether Narp could be involved in the molecular adaptations accompanying drug withdrawal. To this end, we checked the effect of opiate withdrawal on Narp expression in the extended amygdala, a brain region closely linked to the aversive effects of drug withdrawal. We found a marked increase in the number of Narp-positive cells in this region following opiate withdrawal triggered by either low doses of opiate antagonists or by 'natural withdrawal', removal of the morphine pellets used to induce dependence. In contrast, Arc, another 'effector' IEG, was not induced by opiate withdrawal. As expected, pretreatment of animals with clonidine, which blocks opiate withdrawal, suppresses Narp induction in this paradigm. These results implicate Narp in mediating the long-term, aversive behavioral effects induced by opiate withdrawal.
Reti
Irving M
IM
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. imreti@jhmi.edu
Baraban
Jay M
JM
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002097:C-Reactive Protein / Q000096:biosynthesis* / Q000235:genetics; D002452:Cell Count; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D000099153:Pentraxins
D000700:Analgesics; D002097:C-Reactive Protein; D003000:Clonidine; D009270:Naloxone; D009271:Naltrexone; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; D000099153:Pentraxins