Agmatine diminishes behavioral and endocrine alterations in a rat model of post-traumatic stress disorder.

Abstract

Post-traumatic stress disorder (PTSD), is a severe anxiety disorder characterized by associative fear conditioning. Single prolonged stress (SPS) is a widely accepted reliable animal model to stimulate PTSD. Agmatine is an endogenous neuromodulator of stress; however, its effect on PTSD remains to be investigated. This study explored the role of agmatine in conditioned fear response (CFR) in PTSD and highlighted the role of imidazoline receptors in the effect of agmatine. Intra-cerebroventricular (icv) surgery was done in order to facilitate drug administration. Animals were subjected to SPS. Agmatine and the involvement of imidazoline receptors (Iand I) were assessed for their effect in fear conditioning apparatus. During weeks 1, 2, and 3, in CFR, agmatine (40 µg/rat, icv) showed significantly decreased freezing time whereas other doses of agmatine (10 and 20 µg/rat, icv). Imidazoline (Iand I) receptor agonists Moxonidine (25 µg/rat, icv) and 2-BFI, (10 µg/rat, icv) respectively, at their sub-effective doses, with a submaximal dose of agmatine (20 µg/rat, icv) significantly decreased the altered freezing time during weeks 1, 2 and 3 compared to SPS animals. Moreover, the effective dose of agmatine (40 µg/rat, icv) with imidazoline (Iand I) receptor antagonists Efaroxan (10 µg/rat, icv) and Idazoxan (4 µg/rat, icv) respectively does not reversed the effect of agmatine on freezing. Agmatine and its combination with Iand Iagonists, normalized the altered freezing behavior, corticosterone level, organ coefficient of adrenal gland, neuroinflammatory and neurotrophic factor due to SPS during CFR projecting its strong therapeutic effect in SPS induced PTSD.