{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T00:37:34Z","timestamp":1793752654359,"version":"4.6.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg\/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10\u201320 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the \u03b12 adrenergic receptor agonist clonidine (10 \u00b5g\/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg\/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and \u03b12 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg\/kg s.c.)-potentiated startle and clonidine on CRF (2 \u00b5g i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and \u03b12 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.<\/jats:p>","DOI":"10.1017\/s1461145713000308","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T13:01:42Z","timestamp":1366117302000},"page":"1867-1875","source":"Crossref","is-referenced-by-count":35,"title":["Corticotropin-releasing factor (CRF) and \u03b12 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats"],"prefix":"10.1093","volume":"16","author":[{"given":"Paula E.","family":"Park","sequence":"first","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA"},{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro F.","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel E.","family":"Schlosburg","sequence":"additional","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Edwards","sequence":"additional","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gery","family":"Schulteis","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System and Department of Anesthesiology, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George F.","family":"Koob","sequence":"additional","affiliation":[{"name":"Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,1]]},"reference":[{"key":"2019101113500711100_ref1","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1111\/j.1749-6632.1999.tb09284.x","article-title":"The bed nucleus of the stria terminalis. 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