L-DOPA/Capsazepine or L-DOPA/Rimonabant Co-Administration in an Experimental Parkinson Disease Model: Behavioral and Cellular Consequences

Objective: using the 6-OHDA lesion in rats, we evaluated the ability of rimonabant or capsazepine with the addition of L-DOPA in: (1) the severity of LIDs, the dyskinetic effects were assessed using measures of abnormal involuntary movements (AIMs); (2) the protection of dopaminergic cell loss; and (3) in the cytological differences between treatments through analyzing the number of dendritic spines of the striatal medium-sized spiny neurons and the neuropile preservation. Oral co-administration of each antagonist with L-Dopa significantly decreased LIDs. Our data demonstrate that co-administration of L-DOPA with CB1 or TVPR1 receptor antagonists result in a very efficient treatment to reduce AIMs by conserving some functional dopaminergic cells, which implies the well-preserved synaptology of less denervated striatum. Thus, consistent with other reports, cannabinoid antagonist-based therapy would not only be aimed at alleviating specific motor symptoms but also at delaying/arresting the degeneration of striatal and substantia nigra compacta cells.