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In animals, CRF<jats:sub>1<\/jats:sub>appears to primarily mediate CRF-induced anxiety-like responses, but the role of CRF<jats:sub>2<\/jats:sub>during stress is still unclear. Here we report the effects of CRF<jats:sub>1<\/jats:sub>and CRF<jats:sub>2<\/jats:sub>on the magnitude and plasticity of defensive startle responses in mice. Startle plasticity is measured by inhibition of startle by sensory stimuli, i.e., prepulse inhibition (PPI), and is disrupted in patients with panic or posttraumatic stress disorders in which CRF neurotransmission may be overactive. Pharmacological blockade of CRF<jats:sub>1<\/jats:sub>reversed both CRF-induced increases in startle and CRF-induced deficits in PPI. CRF<jats:sub>2<\/jats:sub>blockade attenuated high-dose but not low-dose CRF-induced increases in startle and reduced PPI. Conversely, activation of CRF<jats:sub>2<\/jats:sub>enhanced PPI. CRF had no effect on startle and increased PPI in CRF<jats:sub>1<\/jats:sub>knock-out mice. These data indicate that CRF receptors act in concert to increase the magnitude of defensive startle yet in opposition to regulate the flexibility of startle. These data support a new model of respective CRF receptor roles in stress-related behavior such that, although both receptors enhance the magnitude of defensive responses, CRF<jats:sub>1<\/jats:sub>receptors contravene, whereas CRF<jats:sub>2<\/jats:sub>receptors enhance, the impact of sensory information on defensive behavior. We hypothesize that excessive CRF<jats:sub>1<\/jats:sub>activation combined with reduced CRF<jats:sub>2<\/jats:sub>signaling may contribute to information processing deficits seen in panic and posttraumatic stress disorder patients and support CRF<jats:sub>1<\/jats:sub>-specific pharmacotherapy.<\/jats:p>","DOI":"10.1523\/jneurosci.5760-03.2004","type":"journal-article","created":{"date-parts":[[2004,7,21]],"date-time":"2004-07-21T22:11:36Z","timestamp":1090447896000},"page":"6545-6552","source":"Crossref","is-referenced-by-count":107,"title":["Corticotropin-Releasing Factor Receptors CRF<sub>1<\/sub>and CRF<sub>2<\/sub>Exert Both Additive and Opposing Influences on Defensive Startle Behavior"],"prefix":"10.1523","volume":"24","author":[{"given":"Victoria B.","family":"Risbrough","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard L.","family":"Hauger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda L.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wylie W.","family":"Vale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Geyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2004,7,21]]},"reference":[{"key":"2023041303074103000_24.29.6545.1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1600001"},{"key":"2023041303074103000_24.29.6545.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(00)01082-9"},{"key":"2023041303074103000_24.29.6545.3","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1523\/JNEUROSCI.22-07-02926.2002","volume":"22","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303074103000_24.29.6545.4","doi-asserted-by":"publisher","DOI":"10.1038\/74263"},{"key":"2023041303074103000_24.29.6545.5","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1176\/ajp.144.7.873","volume":"144","year":"1987","journal-title":"Am J Psychiatry"},{"key":"2023041303074103000_24.29.6545.6","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1990.01810140081011"},{"key":"2023041303074103000_24.29.6545.7","doi-asserted-by":"publisher","DOI":"10.1007\/s002130100810"},{"key":"2023041303074103000_24.29.6545.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00002-6"},{"key":"2023041303074103000_24.29.6545.9","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0028-3908(01)00094-6","volume":"41","year":"2001","journal-title":"Neuropharmacology"},{"key":"2023041303074103000_24.29.6545.10","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1176\/ajp.154.5.624","volume":"154","year":"1997","journal-title":"Am J Psychiatry"},{"key":"2023041303074103000_24.29.6545.11","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001404"},{"key":"2023041303074103000_24.29.6545.12","doi-asserted-by":"publisher","DOI":"10.1037\/h0060166"},{"key":"2023041303074103000_24.29.6545.13","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1025-2"},{"key":"2023041303074103000_24.29.6545.14","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0196-9781(01)00386-2","volume":"22","year":"2001","journal-title":"Peptides"},{"key":"2023041303074103000_24.29.6545.15","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050327"},{"key":"2023041303074103000_24.29.6545.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(02)01946-6"},{"key":"2023041303074103000_24.29.6545.17","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0730821.x"},{"key":"2023041303074103000_24.29.6545.18","first-page":"113","volume":"296","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303074103000_24.29.6545.19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb48289.x"},{"key":"2023041303074103000_24.29.6545.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(01)01323-3"},{"key":"2023041303074103000_24.29.6545.21","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300256"},{"key":"2023041303074103000_24.29.6545.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-003-0557-9"},{"key":"2023041303074103000_24.29.6545.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(02)00645-5"},{"key":"2023041303074103000_24.29.6545.24","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00395.x"},{"key":"2023041303074103000_24.29.6545.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1991.tb05539.x"},{"key":"2023041303074103000_24.29.6545.26","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/13.4.643"},{"key":"2023041303074103000_24.29.6545.27","unstructured":"Geyer MA, Dulawa SC (2003) Assessment of murine startle reactivity, prepulse inhibition, and habituation. 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