Intranasal insulin administration improves anxiety- and depressive-like behaviors in PTSD-exposed rats

Post-traumatic stress disorder (PTSD) is a debilitating mental illness that arises after experiencing traumatic events. Insulin is involved in several nervous system functions through widespread receptors across the central nervous system (CNS). We aimed to study the effects of intranasally delivered insulin on behavioral impairments in an animal model of PTSD.

The single prolonged stress (SPS) protocol, which involved 2 h of restraint, 20 min of forced swimming, and exposure to vaporized diethyl ether, was used to induce PTSD-like symptoms in adult male rats. Insulin was administered intranasally (1 IU/day, 5 μl in each nostril) for 14 consecutive days. Anxiety- and depressive-like behaviors were evaluated by the elevated plus maze (EPM) and forced swimming test (FST), respectively. Short-term memory (STM) and long-term memory (LTM) were also assessed using passive avoidance. The protein levels of factors involved in oxidative stress and neuroinflammation, neurotrophic factors, and corticosterone were measured in the hippocampus by ELISA.

Intranasal administration of insulin reduced anxiety- and depressive-like behaviors and LTM impairment induced by SPS. Increased levels of corticosterone, ROS, and TNFα, and levels and decreased levels of SOD, catalase, BDNF, and GDNF were observed in the hippocampus of PTSD-modeled animals. Insulin could reduce oxidative stress and enhance the levels of neurotrophic factors.

These findings suggest that intranasal administration of insulin early after trauma could lead to anxiolytic and antidepressant effects through the likely mechanism of modulating oxidative stress and neurotrophic factors.