This tremor, present predominantly at rest, appears early on in the disease course and causes a significant amount of life distress ( Mansur et al., 2007). Tremor, defined as “a rhythmic and involuntary oscillation of a body part, caused by reciprocal innervations of a muscle, which leads to repetitive, stereotyped contractions with regular frequency and amplitude,” is sometimes considered to be the cardinal symptom of parkinsonism ( Deuschl et al., 2000 Mansur et al., 2007). Regardless of subtype, all forms of parkinsonism share in common four core symptoms: bradykinesia, postural instability, rigidity, and tremor ( Hoehn and Yahr, 1967). Idiopathic Parkinson’s disease is just one member of a broader family of motor disorders known as parkinsonism ( Alvarez et al., 2007), a group that also includes encephalitic, pugilistic, and drug-induced parkinsonism. The current review discusses recent advances in the validation of the TJM model, and illustrates how this model is being used to develop novel therapeutic strategies, both surgical and pharmacological, for the treatment of parkinsonian resting tremor. Overall, these drug-induced TJMs share many characteristics with human parkinsonian tremor, but do not closely resemble tardive dyskinesia. TJMs occur in the same 3–7 Hz frequency range seen in parkinsonian resting tremor, a range distinct from that of dyskinesia (1–2 Hz), and postural tremor (8–14 Hz). TJMs are induced by conditions that also lead to parkinsonism in humans (i.e., striatal DA depletion, DA antagonism, and cholinomimetic activity) and reversed by several antiparkinsonian drugs (i.e., DA precursors, DA agonists, anticholinergics, and adenosine A 2A antagonists). The tremulous jaw movement (TJM) model is an extensively validated rodent model of tremor. Despite its prevalence, and the significant decrease in quality of life associated with it, the pathophysiology of parkinsonian tremor is poorly understood. Parkinsonian resting tremor occurs in a frequency range of 3–7 Hz and can be resistant to available pharmacotherapy. Tremor is a cardinal symptom of parkinsonism, occurring early on in the disease course and affecting more than 70% of patients.

2 Department of Surgery, University of Connecticut Health Center, Farmington, CT, USA.

1 Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, Storrs, CT, USA.

Tremulous jaw movements induced by tacrine in rats appear to share some characteristics with Parkinsonian tremor.Patrick B. Thus, tacrine-induced jaw movements are reduced by antimuscarinic treatment, and most of these movements occur in the parkinsonian tremor frequency range. The vast majority of the movements occurred in rapid “bursts,” and analysis of interresponse times (i.e., the time between each jaw movement) showed that most of the jaw movements occurred within a local frequency range of 3 to 7 Hz. The fifth experiment utilized a slow-motion videotaping system to analyze the temporal characteristics of vacuous chewing induced by 5.0 mg/kg tacrine.

Intrastriatal injections of scopolamine completely blocked tacrine-induced jaw movements. The fourth experiment examined the effect of scopolamine (2.5 to 10.0 ug) injected into the ventrolateral striatum on vacuous jaw movements induced by 5.0 mg/kg tacrine. This effect was reduced, also in a dose-related manner, by the co-administration of the muscarinic antagonist scopolamine in a range of 0.125 to 1.0 mg/kg, but not by N-methylscopolamine. In the first experiment, tacrine produced vacuous chewing in a dose-related manner in a range of 1.25 mg/kg to 1.0 mg/kg. In the present study, five experiments were conducted to provide a pharmacological, anatomical and behavioral characterization of tacrine-induced vacuous jaw movements. Previous work has shown that cholinomimetic drugs induce “vacuous” or non-directed jaw movements in rats.

Tremulous movemnt