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.
ABSTRACT
Temporal lobe epilepsy may be associated with emotional difficulties such as depression and anxiety. Because the amygdala is involved in both epilepsy and emotion, common neural mechanisms in this temporal lobe structure may underlie the emotional disturbances observed in people with epilepsy. The neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) is implicated in many psychopathologies, and 5-HT also modulates amygdala excitability. Therefore, the present study uses the fear-potentiated startle (FPS) paradigm to investigate the effect of neuronal excitability on fear behavior in rats treated with p-chlorophenylalanine (PCPA) to chronically inhibit 5-HT synthesis. PCPA treatment selectively enhanced FPS in individually housed rats. The exaggerated FPS response was reduced to control level by the anticonvulsant phenytoin at 10mg/kg, and phenytoin at 30mg/kg further decreased FPS behavior. These data suggest that a subseizure state of neuronal excitability mediated by low 5-HT in brain fear circuits may be associated with pathological fear behavior.
