Effects of THC, THC acid and CBD on MPP+ or glutamate affected dissociated mesencephalic cultures of mice

Phytocannabinoids become of interest for studies on neuroprotection. Two major events leading to neuronal degeneration are oxidative stress and excitotoxicity. In cell culture systems, these events can be induced by the use of either the complex I inhibitor MPP⁺ or high doses of glutamate. In our study, we investigated the effects of tetrahydrocannabinol (THC), THC acid (THCA) and cannabidiol (CBD) on MPP⁺ or glutamate affected dissociated mesencephalic cultures of mice. On the 8^th day in vitro, cannabinoids (0.001 to 10µM) were administered alone or concomitantly with MPP⁺ (10µM) or glutamate (30µM) for 48h. Using tyrosine hydroxylase immunocytochemistry, dopaminergic neurons were stained and counted. While 10 µM of CBD decreases the dopaminergic cell number, THCA has no effect and THC increases the number of surviving neurons at a concentration of 1 and 10 µM. MPP⁺ treatment results in a degeneration of about a half of the dopaminergic cells. Against this cell degeneration, all chosen phytocannabinoids display neuroprotective effect at 10 µM. Administration of glutamate for 48h leads to a reduction of dopaminergic cell count by about 30%. Phytocannabinoids support the cell survival in glutamate treated cultures significantly already at low concentrations. Cannabinoids might be candidates for neuroprotective agents in disorders in which excitotoxicity and oxidative stress occur.