Intranasal infusion of melanocortin receptor four (MC4R) antagonist to rats ameliorates development of depression and anxiety related symptoms induced by single prolonged stress

IN administration of 100 μg HS014 pre-SPS improved despair behavior in forced swim (FS) immediately after immobilization stress part of SPS protocol. During all 4 intervals of 20 min FS these rats spent less time immobile than rats given vehicle or 3.5 ng HS014. This dose of HS014 also had a long-term beneficial effect manifested as reduction of immobility time in forced swim test performed after SPS. However, both HS014 doses were effective in ameliorating development of anxiety-like behavior after traumatic stress. Thus, rats given IN HS014 prior to SPS exhibited less open arms (OA) visits in elevated plus maze (EPM), spent longer time in OA and less in closed arms, had lower anxiety index, higher risk assessment and more head dips over borders in OA. They also spent longer time in the center of the open field and defecated less. Reduced grooming behavior in EPM was observed with 100 μg HS014. This is the first study revealing pronounced resilience effects of HS014 on development of behavioral symptoms co-morbid with PTSD.