Chronic progesterone treatment of male rats with unilateral 6-hydroxydopamine lesion of the dorsal striatum exacerbates [corrected] parkinsonian symptoms.

Progesterone (PROG) shows neuroprotective effects in numerous lesion models, including a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the possible beneficial effects of PROG on the behavioral and neurochemical impairments incurred in the hemiparkinsonian 6-hydroxydopamine (6-OHDA) model have not been investigated. Vehicle or PROG (4 mg/kg or 8 mg/kg) was daily applied over 13 days after unilateral injection of 6-OHDA into the dorsal striatum of male rats. Turning behavior, foot slips on a horizontal grid, and forelimb use during rearing in a cylinder were observed on days 4, 5, 9, 10, 13, and 14 postlesion, and then the brain samples were analyzed by HPLC-EC. Chronic 8 mg/kg of PROG administration increased the DOPAC/dopamine (DA) ratio in the lesioned striatum, ipsiversive turnings, and the number of hind limb slips and decreased the symmetrical use of forelimbs. Thus, contrary to hypothesis, the chronic treatment with PROG exasperated rather than alleviated the motor impairments in the hemiparkinsonian rats. Because previous studies with the MPTP model had shown protective effects when PROG treatment was administrated before the lesion, our results do not rule out such potential neuroprotective action with prelesion PROG treatment. However, our results raise the question of possible negative interactions between PROG and parkinsonian symptoms in males.