Objective:

The present study was designed to investigate the therapeutic potential of noladin ether- a putative endocannabinoid against MPTP-induced behavioral, biochemical and neurochemical alterations in rats.

Background:

Cannabinoid CB1 receptors are densely expressed in striatal neurons and suggested to influence dopaminergic signaling in basal ganglionic circuitry. Noladin ether is known to be a putative endocannabiod and is reported to modulate cannabinoid receptors. However, least is known about is neuroprotective potential.

Methods:

MPTP (100μg/μl; intranigral) was infused in to substantia nigra pars compacta [SNpc, repeatedly on 1^st, 4^th and 7^th day] in rats. Noladin ether, WIN55, 212-2 as cannabinoid receptor agonists and AM251 a CB1 receptor antagonist was used. Following 1^st MPTP infusion, rats were treated with noladin ether (0.01 and 0.1mg/kg, ip), WIN55, 212-2 (0.1mg/kg, ip), alone or in combination with AM251 (0.025mg/kg, ip) for 21 days to confirm the involvement of the CB₁ receptors. Motor abnormalities were assessed by grip strength, narrow beam walk, open field and rotarodtests on a weekly basis.On 22^nd day rats were sacrificed, and the striatal brain region was used for determining the levels of inflammatory cytokines, dopamine (DA) and its metabolites, GABA and glutamate.

Results:

MPTP produced significant motor deficit, which was accompanied by increase in striatal cytokines and glutamate and a significant deficiency in DA and GABA levels. Both,noladin ether and WIN55, 212-2 attenuated the MPTP-infused motor deficit and restored striatal neurochemical alterations in rats. 30min prior administration of AM251 significantly abrogated the beneficial effects of noladin ether, indicating CB₁ receptor dependency.

Conclusions: The current findings clearly indicate the neuroprotective potential of noladin ether and demonstrate important role of CB1 receptor in neuroinflammation and the striatal neurochemistry. Together, our results suggest that the therapeutic potential of CB1 receptor ligands in the treatment of Parkinson’s disease. 

References: Correa F, Mestre L, Molina-Holgado E, Arevalo-Martin A, Docagne F, Romero E, Molina-Holgado F, Borrell J, Guaza C. The role of cannabinoid system on immune modulation: therapeutic implications on CNS inflammation. Mini Rev. Med. Chem. 2005;5(7):671–5.  Robinson S1, Freeman P, Moore C, Touchon JC, Krentz L, Meshul CK. Acute and subchronic MPTP administration differentially affects striatal glutamate synaptic function. Exp Neurol. 2003 Mar;180(1):74-87.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/noladin-ether-attenuates-mptp-induced-motor-deficit-by-abrogating-pro-inflammatory-cytokines-and-striatal-neurochemical-alterations-in-rats/