Effect of PACAP in 6-OHDA-induced injury of the substantia nigra in intact young and ovariectomized female rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective effects in various neuronal cultures and in models of brain pathologies in vivo. Among others, it protects dopaminergic neurons in vitro, against 6-OHDA- and rotenone-induced injury. Recently, we have shown that PACAP reduces dopaminergic cell loss and ameliorates behavioral outcome following unilateral 6-OHDA-induced injury of the substantia nigra in male rats. However, after castration, PACAP led only to a slight amelioration of the behavioral symptoms. The aim of the present study was to investigate the degree of neuroprotection exerted by PACAP in female rats, using the same model. It was found that PACAP had no effect on the dopaminergic cell loss in intact female rats, only caused amelioration of certain acute behavioral signs. In contrast, PACAP effectively increased dopaminergic cell survival and decreased behavioral deficits in ovariectomized females. These results indicate that the neuroprotective effect of PACAP in a rat model of Parkinson's disease is gender-specific.