Gender-Based Effects of Chronic Nicotine Administration on Hypothalamic Pituitary Adrenal Axis and Indoleamine 2,3 dioxygenase Activity in Rats

Activation of indoleamine 2,3 dioxygenase (IDO) and thus kynurenine production exerts immunosuppressive effects resulting in T lymphocyte inhibition. Stress response as well as nicotine addiction may account for an augmented hypothalamic-pituitary-adrenal (HPA) axis activity. As there is a paucity of studies regarding gender-based differences in HPA axis and IDO activity in relation to chronic nicotine administration, the present study was designed. Adult Albino Wistar male (n=12) and female rats (n=12) were divided into two groups viz control group and nicotine treated group. Control groups received drinking tap water while nicotine-treated groups received nicotine by oral gavage (3.08mg/ml/kg) daily for 21 days. Body weight, serum cotinine and tryptophan concentrations were found to be significantly lowered whereas brain tryptophan and serum corticosterone were significantly raised in nicotine treated females as compared to the male rats. Nicotine treatment decreased brain kynurenine only in males but not in females. However, female control group showed low kynurenine levels than their male counterparts. IDO activity was significantly inhibited in both nicotine treated male and female rats as compared to their respective controls with no significant gender-based differences after drug treatment. Therefore, it could be concluded that chronic nicotine administration results in an inhibition of IDO but an augmented HPA axis activity, latter effect being more pronounced in females. These findings could be targeted for pharmacological interventions against inflammatory disorders and cancers.