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Br J Pharmacol. 2019 Nov 6. doi: 10.1111/bph.14914. [Epub ahead of print]

Inhibition of tremulous jaw movements in rats by memantine-Δ9 -tetrahydrocannabinol combination: neuroanatomical correlates.

Author information

1
Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
2
Timpharm LTD, Moscow, Russia.

Abstract

BACKGROUND AND PURPOSE:

Memantine and marijuana smoking have been previously found to inhibit tremor in parkinsonian patients, however, the observed effects were relatively weak. The tremorolytic efficacy of memantine and cannabinoid co-administration is unstudied. This work aimed to evaluate antitremor activity of memantine-Δ9 -tetrahydrocannabinol combination; additionally, the involvement of some neuroanatomical structures in the regulation of the combination effect was evaluated.

EXPERIMENTAL APPROACH:

Haloperidol-induced tremulous jaw movements in rats were used as a model of parkinsonian-like tremor. To evaluate the role of central receptor systems in the drug effect, receptor-targeting agents were administered locally into certain brain areas.

KEY RESULTS:

Memantine and Δ9 -tetrahydrocannabinol alone were without effect, however, co-administration of the drugs significantly decreased number of haloperidol-induced jaw movements. The antitremor activity of the combination was antagonized (i) by injections of L-glutamate into the dorsal striatum, entopeduncular nucleus, substantia nigra pars reticulata, globus pallidus, supratrigeminal and trigeminal motor nuclei but not into the subthalamic and cuneiform nuclei; (ii) by injections of CGS 21680 into the ventrolateral striatum; (iii) by injections of bicuculline into the rostral part of the parvicellular reticular nucleus.

CONCLUSION AND IMPLICATIONS:

Memantine and Δ9 -tetrahydrocannabinol supra-additively inhibit haloperidol-induced tremulous jaw movements. Apparently, the co-administration of the drugs might be a new approach to the treatment of tremor. The presented results identify brain areas influencing parkinsonian-like tremor in rats; these data can help advance the development of novel treatments for repetitive involuntary movements.

KEYWORDS:

A2A receptors; GABAA receptors; glutamate receptors; haloperidol; memantine; tremulous jaw movements; Δ9-tetrahydrocannabinol

PMID:
31696510
DOI:
10.1111/bph.14914

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