{"title":"5-HT<sub>2A</sub> Receptor Activation Normalizes Exaggerated Fear Behavior in <i>p</i>-Chlorophenylalanine (PCPA)-Treated Rats.","authors":"Cathryn R Hughes, Lee Tran, N Bradley Keele","doi":"10.4236/jbbs.2012.24053","DOIUrl":null,"url":null,"abstract":"<p><p>Deficits in serotonin (5-hydroxytryptamine, 5-HT) neurotransmission are implicated in abnormal emotional behaviors such as aggression, anxiety, and depression. However, the specific 5-HT receptor mechanisms involved are not well understood. The role of 5-HT<sub>2</sub> receptors in fear potentiated startle, (FPS) was examined in rats chronically treated with <i>p</i>-chlorophenylalanine (PCPA) to reduce brain 5-HT. PCPA-treated rats show an enhanced magnitude of FPS. Systemic administration of the 5-HT<sub>2</sub> receptor agonist (±)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride (DOI) reduced FPS in both PCPA-treated and saline (SAL)-treated control animals, normalizing the exaggerated fear response in PCPA-treated rats. In both SAL- and PCPA-treated animals, the DOI-induced reduction of learned fear was reversed by the 5-HT<sub>2</sub> antagonist ketanserin, but not by the 5-HT<sub>2B/2C</sub> antagonist SB 206553. Together, these findings suggest 5-HT<sub>2A</sub> receptors are critical regulators of learned fear, and that 5-HT<sub>2A</sub> receptors may be an important pharmacological target to normalize exaggerated learned fear resulting from chronic 5-HT-ergic disruption.</p>","PeriodicalId":15186,"journal":{"name":"Journal of Behavioral and Brain Science","volume":"2 4","pages":"454-462"},"PeriodicalIF":0.0000,"publicationDate":"2012-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003617/pdf/nihms-1874699.pdf","citationCount":"10","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Behavioral and Brain Science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4236/jbbs.2012.24053","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 10
Abstract
Deficits in serotonin (5-hydroxytryptamine, 5-HT) neurotransmission are implicated in abnormal emotional behaviors such as aggression, anxiety, and depression. However, the specific 5-HT receptor mechanisms involved are not well understood. The role of 5-HT2 receptors in fear potentiated startle, (FPS) was examined in rats chronically treated with p-chlorophenylalanine (PCPA) to reduce brain 5-HT. PCPA-treated rats show an enhanced magnitude of FPS. Systemic administration of the 5-HT2 receptor agonist (±)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride (DOI) reduced FPS in both PCPA-treated and saline (SAL)-treated control animals, normalizing the exaggerated fear response in PCPA-treated rats. In both SAL- and PCPA-treated animals, the DOI-induced reduction of learned fear was reversed by the 5-HT2 antagonist ketanserin, but not by the 5-HT2B/2C antagonist SB 206553. Together, these findings suggest 5-HT2A receptors are critical regulators of learned fear, and that 5-HT2A receptors may be an important pharmacological target to normalize exaggerated learned fear resulting from chronic 5-HT-ergic disruption.