Therapeutic Potential of 5-HT6 Antagonist SB399885 in Traumatic Stress Disorder.

Abstract

Post-traumatic stress disorder is an anxiety disorder for which current therapies are not effective. The 5-Hydroxytryptamine6 receptor antagonist SB399885 has been reported to have an anxiolytic effect. Hence, the current investigation was undertaken to evaluate its efficacy in post-traumatic stress disorder. Rats were placed in the operant box and given 3 foot shocks at intervals of 1 min. The following day the duration of freezing was recorded. For the enhanced sustained prolonged stress (ESPS), the rats were subjected to various stressors such as restraint stress (2 h), forced swim (20 min), and anesthesia, followed by a foot shock for 4 s. The rats were then subjected to the elevated plus maze. Treatment with SB399885 (1 and 3 mg/kg, I. p.) was found to significantly decrease the freezing time in the contextual fear conditioning model. Rats subjected to ESPS spent greater time in the open arm of the elevated plus maze when administered SB399885 at the above mentioned doses. The treatment had no effect on locomotor activity. SB399885 decreased the 5-hydroxytryptamine levels in the amygdala at doses that were effective in the above animal models. 5-Hydroxytryptamine6 antagonists may hold potential in the treatment of post-traumatic stress.