The Role of Hypothalamus-Pituitary-Adrenal (HPA) Axis on Anti-Inflammatory Effects of the Trifluoperazine in Male Rats

Previous studies, have been shown the anti-inflammatory effects of the trifluoperazine. The present study was performed to investigate the role of hypothalamus-pituitary-adrenal (HPA) axis activity as a possible mechanism for these effects. This experimental study was carried out on 100 male rats. Inflammation was induced by intraplantar injection of 0.1 ml of 0.5% carrageenan solution in to the rat’s left hind paw. Rats were divided randomly into three groups of control, the adrenalectomized (ADX) and the CRH antagonist receiving group. Adrenalectomy was performed bilaterally on the rats. The CRH antagonist at 20 µg/rat was administered intraventriculary, and Trifluoperazine (0.2 and 8 mg/kg) was used intraperitoneally (i.p) on the rats. Four hours after injections, paw edema was assessed by calculating the volume changes and extravasations of Evans blue dye. Furthermore, the serum levels of prolactin and ACTH were measured. Both doses of trifluoperazine significantly reduced the paw volume and tissue content of Evans blue dye in the control and ADX rats. Therefore, the paw edema induced by carrageenan, was reduced in the control and ADX groups by 48% and 65%, and the tissue content of Evans blue dye was decreased by 60% and 20% respectively. In the CRH antagonist receiving rats, different doses of drug reduced the volume of inflamed paw by 50%. Adrenalectomy induced an increase in the ACTH level 9 times more than control and both doses of the trifluoperazine blocked this elevation by 82%. Adrenalectomy procedure had no significant influence on plasma level of prolactin. These results suggest that trifluoperazine may have an in-vivo anti-inflammatory effect on experimental model, which possibly is independent of HPA axis activity.