5-HT_2A Receptor Activation Normalizes Exaggerated Fear Behavior in p-Chlorophenylalanine (PCPA)-Treated Rats

Cathryn R. Hughes, Lee Tran, N. Bradley Keele

Department of Psychology & Neuroscience, Baylor University, Waco, USA.

DOI: 10.4236/jbbs.2012.24053                

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 pchlorophenylalanine (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-HT_2A receptors are critical regulators of learned fear, and that 5-HT_2A receptors may be an important pharmacological target to normalize exaggerated learned fear resulting from chronic 5-HT-ergic disruption.

Keywords

Fear Conditioning; Startle Reflex; 5-HT2; DOI; Ketanserin; SB 206553

Conflicts of Interest

The authors declare no conflicts of interest.

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