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Objectives: Progesterone has been reported to have a neuroprotective role in depression-like rats in a hemiparkinsonian model of the disease. In this work, we investigate if this hormone affects the three principal neurochemicals striatal systems (dopaminergic, glutamatergic, and GABAergic) that are involved in the physiopathology of the disease in a hemiparkinsonim male rat model at 8 weeks post-chemical injury., Methods: For this purpose, we design three experimental groups: (1) sham group; (2) hemiparkinsonian group; and (3) hemiparkinsonian group subcutaneously injected with progesterone at 7 days post-chemical injury. Animals were tested in an automated rotational device at 8 weeks post-chemical injury. After behavioral test, K(+)-evoked [(3)H]-dopamine, [(3)H]-glutamate, and [(3)H]-gamma aminobutyric acid release from striatum slices were analyzed by superfusion experiments., Results: The hemiparkinsonian group showed distinctive alterations that are produced by neurodegeneration of left nigrostriatal dopaminergic pathway by 6-hydroxydopamine hydrobromide (6-OHDA). On the other hand, the administration of progesterone 7 days after the injection of the neurotoxin was able to (1) improve the K(+)-evoked [(3)H]-dopamine release from the damaged striata (left); (2) avoid significant increase in the K(+)-evoked [(3)H]-glutamate release from the left striata; and (3) progesterone does not modify the K(+)-evoked [(3)H]-gamma aminobutyric acid release from the left striata., Discussion: These results suggest that progesterone does have neuroprotective and neuromodulatory effects on striatal neurotransmission systems in the hemiparkinsonian male rats. The possible mechanisms would involve genomic and non-genomic actions of this neuroactive steroid which would modulate the activity of dopaminergic, glutamatergic, and GABAergic pathways.

Abstract: Hemiparkinsonism induced by 6-hydroxydopamine (6-OHDA) injected in left corpus striatum is a recognized model of motor deficits in rats. Some reports concerning motor deficits indicate a favorable response to steroid administration in hemiparkinsonian animals. However, there is no much information regarding progesterone administration in relation to cognitive and affective dysfunctions. Here we could confirm earlier reports regarding a mild deficit of memory and a noticeable depressive-like behavior 4weeks after injecting 6-OHDA. We also present some evidence that progesterone could be – when administered 7days after the injection of 6-OHDA – a possible neuroprotector concerning both motor deficits as well as cognitive — memory- and depression-like behaviors. The affective deficit was reverted by administering the tricyclic antidepressant imipramine. Since Parkinson''s disease is a conspicuous cause of psycho-organic decline in human beings, it would be important to be able of dealing early with non-motor indicators in order to use prospective neuroprotectors to prevent the progression of the disease. [Copyright &y& Elsevier]