Neuroprotective Effects of Delta-9-Tetrahydrocannabinol in a Marmoset Parkinson Model

Abstract

The present medication in Parkinson's disease (PD) is unable to stop or slow down the progression of the dis- ease. Therefore pharmacological intervention at crucial steps in the neuronal cell death processes would be a better stra- tegy. Cannabinoids are potent neuroprotective compounds in models of oxidative stress and excitotoxicity and offer po- tential protection in models of PD. Therefore the present study determines the neuroprotective effects of � 9 - tetrahydrocannabinol (� 9 -THC) in the marmoset 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model on beha- vior and pathology. Twelve marmoset monkeys were treated with a total cumulative dose of 6 mg/kg MPTP in 9 days. Seven of these animals received simultaneously a daily oral dose of � 9 -THC (4 mg/kg) and five animals received simulta- neously vehicle for 27 days. The parkinsonian symptoms were observed daily and locomotor activity and hand-eye coor- dination were tested once a week during the experimental period. Postmortem, dopamine levels in the striatum were ana- lyzed and tyrosine hydroxylase immunohistochemistry was applied to determine viable dopaminergic neurons in the sub- stantia nigra. � 9 -THC has no protective effects on any parameter. These negative results might be related to the severity of the cell death induction by MPTP in relation to the low dose of � 9 -THC used in this Parkinson model.