Neostriatal muscarinic receptor subtypes involved in the generation of tremulous jaw movements in rodents - Implications for cholinergic involvement in Parkinsonism

Several studies have shown that a number of pharmacological and neurochemic al conditions in rats can induce jaw movements that are described as "vacuo us" or "tremulous". For several years, there has been some debate about the clinical significance of various drug-induced oral motor syndromes. Nevert heless, considerable evidence now indicates that the non-directed, chewing- like movements induced by cholinomimetics have many of the characteristics of parkinsonian tremor. These movements are characterized largely by vertic al deflections of the jaw, which occur in the same 3-7 Hz peak frequency th at is typical of parkinsonian tremor. Cholinomimetic-induced tremulous jaw movements are suppressed by a number of different antiparkinsonian drugs, i ncluding scopolamine, benztropine, L-DOPA, apomorphine, bromocriptine, ropi nirole, pergolide, amantadine, diphenhydramine and clozapine. A combination of anatomical and pharmacological research in rats has implicated M-4 rece ptors in the ventrolateral neostriatum in the generation of tremulous jaw m ovements. Mice also show cholinomimetic-induced jaw movements, and M-4 rece ptor knockout mice demonstrate subtantially reduced levels of jaw movement activity, as well as increased locomotion. Taken together, these data are c onsistent with the hypothesis that a centrally-acting M4 antagonist may be useful as a treatment for parkinsonian symptoms, including tremor. (C) 2001 Elsevier Science Inc. All rights reserved.