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

• Published in: Life sciences (1973) Vol. 68; no. 22; pp. 2579 - 2584
• Main Authors: Salamone, John D., Correa, Merce, Carlson, Brian B., Wisniecki, Anna, Mayorga, Arthur J., Nisenbaum, Eric, Nisenbaum, Laura, Felder, Christian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 27.04.2001
• Subjects: Acetylcholine; Acetylcholine - pharmacology; Animals; Basal ganglia; Humans; Jaw; Mice; Mice, Knockout; Motor; Motor Activity - drug effects; Motor Activity - physiology; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Neostriatum - metabolism; Parkinson; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - physiopathology; Pilocarpine - pharmacology; Rats; Receptor, Muscarinic M4; Receptors, Muscarinic - metabolism; Tremor; Tremor - drug therapy; Tremor - physiopathology; Basal ganglia; Acetylcholine; Tremor; Motor; Parkinson
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(01)01055-4

Several studies have shown that a number of pharmacological and neurochemical conditions in rats can induce jaw movements that are described as “vacuous” or “tremulous”. For several years, there has been some debate about the clinical significance of various drug-induced oral motor syndromes. Nevertheless, 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 vertical deflections of the jaw, which occur in the same 3–7 Hz peak frequency that is typical of parkinsonian tremor. Cholinomimetic-induced tremulous jaw movements are suppressed by a number of different antiparkinsonian drugs, including scopolamine, benztropine, L-DOPA, apomorphine, bromocriptine, ropinirole, pergolide, amantadine, diphenhydramine and clozapine. A combination of anatomical and pharmacological research in rats has implicated M 4 receptors in the ventrolateral neostriatum in the generation of tremulous jaw movements. Mice also show cholinomimetic-induced jaw movements, and M 4 receptor knockout mice demonstrate subtantially reduced levels of jaw movement activity, as well as increased locomotion. Taken together, these data are consistent with the hypothesis that a centrally-acting M4 antagonist may be useful as a treatment for parkinsonian symptoms, including tremor.