Journal
JOURNAL OF NEUROCHEMISTRY
Volume 74, Issue 1, Pages 199-208Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1046/j.1471-4159.2000.0740199.x
Keywords
morphine; naltrexone; corticotropin-releasing factor antagonist; striatum; nucleus accumbens; amygdala
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Funding
- NIDA NIH HHS [DA08227] Funding Source: Medline
- NIMH NIH HHS [MH45481, MH53199] Funding Source: Medline
- NATIONAL INSTITUTE OF MENTAL HEALTH [R37MH045481, R29MH045481, R01MH045481] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P01DA008227] Funding Source: NIH RePORTER
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Previous studies indicate that corticotropin-releasing factor (CRF) contributes to the anxiety-like and aversive states associated with drug-induced withdrawal. The present study extends this work by analyzing the CRF receptor subtype involved in withdrawal responses. First, the influence of a selective CRF receptor-1 (CRF-R1) antagonist, CP-154,526, on opiate withdrawal behavior was examined. Pretreatment with the CRF-R1 antagonist significantly attenuated several behavioral signs of naltrexone-induced morphine withdrawal, including writhing, chewing, weight loss, lacrimation, salivation, and irritability, measured during the first hour of withdrawal. Next the expression of CRF-R1 was determined as a second measure of the involvement of this receptor in opiate withdrawal. Naltrexone-induced morphine withdrawal resulted in down-regulation of CRF-R1 mRNA in several brain regions, including the frontal cortex, parietal cortex, striatum, nucleus accumbens, and amygdala, but not in the hypothalamus or periaqueductal gray. Expression of CRF-R2, the other major CRF receptor subtype, was not down-regulated significantly by withdrawal in any of the regions examined, although morphine alone significantly increased levels of this receptor subtype. Taken together, the behavioral and receptor regulation findings indicate that CRF-R1 is the primary mediator of the actions of the CRF system on opiate withdrawal, although it is possible that CRF-R2 contributes to the response.
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