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 how imidazoline receptors contribute to 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 (I1 and I2) 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 as compared to other doses of agmatine (10 and 20 µg/rat, icv). Imidazoline (I1 and I2) 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 (I1 and I2) receptor antagonists Efaroxan (10 µg/rat, icv) and Idazoxan (4 µg/rat, icv) respectively does not show a significant effect on freezing. Agmatine and its combination with I1 and I2 agonists, normalized the altered freezing behavior due to SPS during CFR projecting its strong therapeutic implication for CFR in SPS induced-PTSD.