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PubMed1991

Tremor in reflex sympathetic dystrophy.

Postural hand tremor was quantitatively investigated on both sides in 21 patients suffering from unilateral reflex sympathetic dystrophy of the upper extremity. On the affected side, enhanced tremor amplitude, with a mean tremor frequency of 7.2 Hz, was found in 57% of the patients. The appearance of tremor did not correlate to the occurrence of a single clinical symptom of reflex sympathetic dystrophy. On loading with increasing weight, the frequency of this pathological tremor shifted toward lower values, as it is found in physiological tremor. However, the peak frequencies of the electromyogram remained more or less stable. On recovery from this condition, the reflex sympathetic dystrophy tremor disappeared. Acute sympatholytic intervention could normalize reflex sympathetic dystrophy tremor. This would suggest that the sympathetic supply of the affected extremity contributes to the tremor in reflex sympathetic dystrophy. In conclusion, it is suggested that reflex sympathetic dystrophy should be included among the causes of tremor. According to our findings, tremor in reflex sympathetic dystrophy should be regarded as an enhanced physiological tremor.

Electromyography↗
PubMed1999

Validity of a performance-based test of function in essential tremor.

BACKGROUND: The central factor influencing therapeutic decisions in essential tremor (ET) is the functional impact of the tremor. Neither the neurological examination nor computerized tremor analysis measures function. Questionnaires may assess function, but data are highly subjective. Performance-based tests of functional impairment provide an alternative means with which to assess the functional impact of ET. OBJECTIVE: To determine the internal consistency and validity of a performance-based measure of functional impairment in ET. METHODS: Subjects with ET from a community in northern Manhattan, NY, and from a clinic and control subjects each underwent a 2 1/2-hour evaluation including 12 screening questions for ET, a 31-item Tremor Disability Questionnaire to assess the functional impact of tremor, a 26-item Videotaped Tremor Examination that was rated by a neurologist, a 15-item, 10-minute Performance-Based Test, and Quantitative Computerized Tremor Analysis. Internal consistency was assessed with Cronbach alpha. The correlation between the Performance-Based Test and these other measures of tremor was assessed by means of correlation coefficients (r). RESULTS: There were 50 ET cases and 51 normal control subjects. The Performance-Based Test was internally consistent (Cronbach alpha = .92). It also demonstrated validity among cases; the total score correlated with the total number of screening questions answered yes (r = 0.44; P = .001), the total score on the Tremor Disability Questionnaire (r=0.55; P<.001), the total score on the Videotaped Tremor Examination (r=0.71; P<.001), and multiple physiological measures recorded during Quantitative Computerized Tremor Analysis. CONCLUSIONS: A valid performance-based test was developed to objectively assess functional capacity in patients with ET. This test would be useful in therapeutic trials, where it would provide an objective means to quantify the functional impact of tremor.

Aged↗
PubMed2000

Validity and test-retest reliability of a disability questionnaire for essential tremor.

BACKGROUND: One important outcome in clinical trials is patients' own opinions about whether the medication alleviates their symptoms and improves their ability to function. A valid and reliable method with which to assess this subjective information is important. OBJECTIVE: To determine the validity and test-retest reliability of the Columbia University Disability Questionnaire for Essential Tremor (ET). METHODS: Patients with ET underwent a 2.5-hour evaluation, including a 36-item tremor disability questionnaire, to assess the functional impact of tremor, a 26-item videotaped tremor examination rated by a neurologist, a 15-item performance-based test, and quantitative computerized tremor analysis. We determined the validity and test-retest reliability of the tremor disability questionnaire. Correlations between variables were assessed using Pearson's correlation coefficients and test-retest reliability with the weighted kappa statistic. RESULTS: Ninety-five patients with ET participated. The score on tremor disability questionnaire correlated with the neurologist's clinical ratings (r = 0.57, p <0.001) and the total score on the performance-based test (r = 0.69, p < 0.001). Correlations with quantitative computerized tremor analysis results were less robust, but each remained significant, including mean amplitude of dominant arm tremor while arms were extended (r = 0.56, p <0.001), while drawing a spiral (r = 0.42, p = 0.01), and while pouring (r = 0.34, p = 0.04). The questionnaire was readministered to 32 subjects, and the test-retest reliability was substantial (weighted kappa = 0.67). CONCLUSIONS: This Tremor Disability Questionnaire demonstrated substantial reliability, and it correlated with multiple measures of tremor severity, including a neurologist's clinical ratings, a performance-based test of function, and quantitative computerized tremor analysis results. The questionnaire would be useful in clinical trials in which it could be used as a reliable and valid tool to assess disability in ET.

Activities of Daily Living↗
PubMed2003

Community-based data on associations of disease duration and age with severity of essential tremor: implications for disease pathophysiology.

The pathophysiology of essential tremor (ET) is not well understood, although the tremor often worsens over time. Several processes could contribute, including the inherent worsening of the underlying disease with increasing disease duration and the effects of aging on the nervous system. Our objective was to examine the associations of disease duration and age with tremor severity in ET. Cases were ascertained from a community-based study of ET in northern Manhattan, New York. A neurologist rated tremor severity using a clinical rating scale and assigned a total tremor score (0-36 [maximum]). Analyses were repeated in a sample of cases from a tertiary referral center, the Neurological Institute of New York. There were 55 cases from the community-based study (mean age, 72.1 years, mean disease duration, 13.2 years). Disease duration was associated with the total tremor score (r = 0.30; P = 0.02). Age was associated with the total tremor score (r = 0.30; P = 0.025). In a linear regression analysis the dependent variable was the total tremor score and independent variables were disease duration, age gender. Duration (beta = 0.11; P = 0.02) and age (beta = 0.10; P = 0.02) were independently associated with the total tremor score. Results were similar in 79 ET cases from the Neurological Institute. Disease duration and age were independently associated with tremor severity in ET. This suggests that the reported increase in tremor severity may be related to the inherent worsening of the disease with increasing duration that this is independent of age and age-related processes like neuronal attrition and change in tremor frequency.

Adolescent↗
PubMed2003

Multiple sclerosis tremor and the Stewart-Holmes manoeuvre.

The objective of this study is to define tremor and cerebellar dysfunction and determine whether kinetic and postural tremor correlate with cerebellar dysfunction in patients with multiple sclerosis (MS). Cerebellar symptoms such as dysmetria often interfere with tremor evaluation in MS. The Stewart-Holmes (SH) manoeuvre, which has been recently quantified, may offer a selective evaluation of cerebellar dysfunction in such patients. Thirty-two patients with definite MS and arm tremor were evaluated (simplified Fahn tremor scale for kinetic and postural tremor, finger-to-nose test, clinical SH manoeuvre, quantitative study of the SH manoeuvre). Median severity of kinetic and postural tremor on the most disabled side was, respectively, 2 (range 0-4) and 1.5 (range 0-4). Clinical SH scores were moderately correlated to quantified SH measures (r = 0.36, P < 0.05). Kinetic and postural tremors were strongly correlated (r = 0.73, P < 0.0001) but did not correlate with clinical or quantified SH scores. Patients with bilateral tremor had higher scores for quantified SH, and a trend to higher clinical SH and finger-to-nose scores than patients with unilateral tremor. Although clinically associated, cerebellar dysfunction and tremor may be partly independent symptoms, suggesting they may relate to dysfunction of different neuronal systems. The SH manoeuvre should be part of the evaluation of MS patients considered for surgery of tremor.

Adult↗
PubMed2007

Interest in participating in clinical research: A study of essential tremor patients.

Enrolling essential tremor (ET) patients in clinical research can be challenging. Investigators can maximize recruitment by targeting patient subgroups with greater interest in participation. Nothing has been published on factors that are associated with higher levels of interest in participation. The objective of this study was to identify factors associated with higher levels of interest in participating in clinical research on ET. A total of 149 ET patients were questioned about level of interest in participating in future research. Two questions were used, although one was of primary interest. Interest was rated from 0 to 10 (maximal). Data were collected on demographic factors, family history, and tremor-related disability. Tremor severity was assessed. The mean level of interest was 8.0 +/- 2.3. Level of interest was not related to age of tremor onset, tremor duration, tremor severity, extent of tremor-related disability, or use of tremor medication. Level of interest was related to family history of tremor (P < 0.05), concern that other family members might develop tremor (P < 0.05), >2 versus 0 live births in women (P < 0.05), the view that the tremor worsens with age (P < 0.05), and presence of head tremor (P = 0.05). A variety of factors were identified that were associated with greater interest in participating in clinical research. These observations should be assessed in additional patient samples. Investigators may use our observations to identify and target patients for clinical trials and other research.

Biomedical Research↗
PubMed1987

Essential tongue tremor.

Twenty patients with tongue tremor associated with essential tremor are reported. Patients were unaware of the tongue tremor, and voice disturbance was a complaint in only one patient. Three patients had an isolated tongue tremor. Hand tremor was present in 16 patients. Dystonia, myoclonus, and tremor of other body parts were present in some patients. Three patients had a mild-to-moderate dysarthria. The frequency of tongue tremor (4-8 Hz) was identical to hand tremor. The intravenous infusion of ethanol suppressed tongue tremor. Therapy with propranolol, primidone, or clonazepam also reduced tongue tremor amplitude. Tongue tremor is a common finding in some essential tremor patients but often there are no symptoms.

Adolescent↗
PubMed2004

Augmented visual feedback increases finger tremor during postural pointing.

Physiological tremor in the upper limb of eight adults was examined during the performance of a unilateral pointing task under conditions where the visual feedback, limb used and target size were altered. All subjects were required to aim a hand-held laser pointer at a circular target 5.5 m away with the goal of keeping the laser emission within the centre of the target. Visual feedback was defined as either normal vision (NV) of their limb tremor, where the laser was switched off, or augmented vision (AV) where the laser was switched on. Postural tremor from the segments of the upper limb, forearm muscle EMG activity, and target accuracy measures were recorded and analysed in the time and frequency domains. Accuracy-tremor relations were assessed using cross correlation and linear regression. Results revealed a high degree of similarity in the general pattern of the tremor output seen for each limb segment across conditions with only scalar (amplitude) changes being seen as a function of the different constraints imposed. For any single condition the tremor amplitude increased from proximal to distal segments. The frequency profile for the tremor in any segment displayed two prominent frequency peaks (at 2-4 Hz and 8-12 Hz). A third, higher frequency peak (18-22 Hz) was observed in the index fingers only. Across all conditions significant coupling relations were observed only between the hand-finger and forearm-upper arm segment pairs. Altering the visual feedback was shown to have the greatest effect on limb tremor with increased tremor and EMG activity and decreased coupling being seen under AV conditions. In trying to reduce tremor output when the augmented feedback was provided novice subjects instead increased muscle activity which resulted in increased tremor. Overall these results indicate that the physiological tremor output observed in neurologically normal subjects is not simply the product of intrinsic oscillations but is influenced by the nature of the task being performed.

Adult↗
PubMed1982

Effects of lesioning basal ganglia nuclei and output pathways on tremorine-induced tremor in rats.

The tremor produced by muscarinic cholinomimetics is believed to originate in the neostriatum but the efferent pathways are unknown. The intensity and frequency of tremor induced by tremorine was measured in the hindlegs of rats with unilateral basal ganglia lesions. A kainic acid lesion of one neostriatum reduced tremor intensity in the contralateral leg (CL). Unilateral electrolesions of the globus pallidus and nucleus accumbens had no effects on tremor. Both entopeduncular and subthalamic nuclei lesions reduced the frequency and intensity of tremorine tremor in the CL leg. The subthalamic lesion also increased tremor intensity and frequency in the ipsilateral leg. Lesions were made in some brain areas that receive basal ganglia efferent projections. Peak tremor intensity and frequency in both legs was greatly reduced by unilateral decortication. Unilateral lesions of the habenula, red nucleus and pedunculopontine nucleus had no effects on tremor intensity but reduced peak tremor frequency. Lesions of the substantia nigra and periaqueductal gray area had no effects on tremor. Unilateral removal of the superior colliculus reduced tremor intensity in both legs. The findings suggest that intensity and frequency of tremor are influenced by different basal ganglia efferent pathways; intensity involves strio-entopeduncular-cortical projections and frequency is determined by projections to midbrain and brainstem. The superior colliculus, with many muscarinic receptors, may be a direct target area for tremorine.

Animals↗
PubMed1993

Ambulatory monitoring of tremor and other movements before and after thalamotomy: a new quantitative technique.

Tremor, e.g. in Parkinson patients, often shows large spontaneous fluctuations in severity over the day, to such an extent that a short observation is usually not sufficient to assess the overall severity or the effect of a treatment. Since momentary impressions of the tremor can thus be misleading, long-term ambulatory recordings would be helpful in the evaluation of severity and treatment effectiveness. As existing methods for long-term tremor registration have several shortcomings, a new method is proposed: an algorithm was designed to discriminate tremor from other movements and to describe the amount (i.e. the proportion of tremor or movements per time unit) as well as the intensity (i.e. average acceleration amplitude) of the two types of movement. In the evaluation of the severity of tremor both the amount and intensity of tremor episodes are of importance. The algorithm was tested on 24-h analog tape recordings of wrist-movement in 10 young and 10 aged controls, as well as in 8 patients with tremor--both before and after a tremor relieving thalamotomy. The algorithm scored movements as 'tremor' exclusively in patients prior to the operation. Fluctuations in tremor severity over the day were detected, and tremor could be discriminated from non-pathological movements. Moreover, following thalamotomy, motor slowing (bradykinesia) was detectable using this algorithm. Based on these test results, a miniaturized device in wrist-watch format is now being developed for long-term registrations.

Adult↗
PubMed1996

Role of the stretch reflex in oxotremorine tremor.

Although the basic mechanism for parkinsonian tremor is known to be central, the case for the oscillator(s) of physiological tremor and shivering is still a matter of dispute. In this case, an important role has been proposed for muscle afferents. Oxotremorine tremor has in common with shivering its frequency range (10-28 Hz) and the co-contraction of flexors and extensors. On the other hand, in contradistinction, it can be blocked by atropine, as is the case with parkinsonian tremor. Thus it was of interest to analyze the role of muscle afferents in the production and maintenance of oxotremorine tremor in the acutely decorticated cat. This was studied with two experimental approaches. In one, either a front or hind limb of a cat was completely deafferented by dorsal rhizotomy and the tremor activity recorded electromyographycally in a pair of antagonistic muscles. In the other, the nerve and muscle electrical activity and force produced by the tremoring muscle (gastrocnemius) were recorded simultaneously. Tremor activity was induced by oxotremorine injection (200-750 micrograms/kg i.p.) given at different postoperative periods. The drug induced a regular tremor in the chronically deafferented animals (3 weeks to 5 months) but not in the acutely deafferented limb (3 hrs after dorsal rhizotomy). The tremor observed in the former group was very regular and had the same frequency range (10-28 Hz) for both normal and deafferentd sides. Section of all the muscle afferents of a given pool (agonist and its main synergist) did not have any effect on the regularity and frequency of the oscillation (tremor) of that pool. The role of other muscle and/or cutaneous afferents, although perhaps of some importance, remains unclear. A pure spinal mechanism to account for the regular oscillations (tremor) is proposed.

Animals↗
PubMed1987

Modification of drug-induced tremor by systemic administration of kainic acid and quisqualic acid in mice.

The effects of excitatory amino acids, kainic acid and quisqualic acid, on the tremorine- and harmaline-induced tremor were quantitatively examined in mice using the power spectral analyzing method. The severity of the tremor was determined quantitatively in terms of the cumulative sum of the mean square value of the data. Kainic acid enhanced the tremor induced by tremorine but depressed the tremor induced by harmaline. Quisqualic acid depressed the tremor induced by both tremorine and harmaline in a dose-dependent manner. Kainic acid shifted the frequency of each component of the tremor induced by tremorine to the high frequency side, but quisqualic acid did not affect the frequency of tremor of the tremor induced by tremorine. The frequency of tremor of the tremor induced by harmaline was shifted by both excitatory amino acids to the low frequency side, and another component of tremor in the power spectral densities developed, of which the mean square values were very small. The present results suggest that, at least in part, the glutamatergic system can take a role on the modification of drug-induced tremor.

Animals↗
PubMed2005

Nicotine pretreatment diminished physostigmine-induced tremor in rats.

The aim of this work was evaluate the effects of acute and chronic nicotine pretreatment in the physostigmine-induced tremor in rats. Wistar male rats (3-4 months) were pretreated acutely with different nicotine doses (0, 0.1, 0.5 or 1.0 mg/kg) 10 min before physostigmine (0 and 0.5 mg/kg) treatment and then the tremor was registered by computerized system for 10 min. In another group, rats were pretreated acutely with 0.1 mg/kg of nicotine, recovered at different times (30 or 70 min), and were registered for physostigmine-induced tremor. Nicotine was also used chronically with equal doses for 8 days and recovered at 2, 7 or 21 days before registration of physostigmine-induced tremor. Tremor spectral analysis was performed for amplitude and frequency quantification. Our data show that the acute and chronic nicotine pretreatments alter physostigmine spectrum profile. Nicotine decreased physostigmine-induced tremor amplitude (p<0.05), without changing its tremor frequency. In acutely pretreated rats, recovery experiments showed return of physostigmine-induced tremor for control levels after 70 min, but after 8 days of chronic nicotine pretreatment recovery was delayed 3 weeks. The data analysis shows that acute or chronic nicotine administration can alleviate the physostigmine-induced tremor. Chronic nicotine pretreatment has a long tremor alleviation effect of physostigmine-induced tremor. Possible mechanisms involving the nicotine effects on the physostigmine-induced tremor are discussed.

Animals↗
PubMed2000

Determinants of physiologic tremor in a large normal population.

OBJECTIVES: It has been well established that peripheral mechanical resonant factors as well as central mechanisms may play a role in the generation of physiological tremor (PT). Furthermore it has been postulated that subject's attributes like age and sex might influence PT. The present study was designed to quantify these influences on PT in a large normal population. METHODS: Physiological hand and finger tremors were measured in a group of 117 normal subjects between 20 and 94 years of age using accelerometry and surface EMG recordings from the forearm flexor and extensor muscles. The hand tremor was measured in a postural position with and without weight, and the finger tremor was recorded with the arm outstretched, forearm supported and hand supported. Hand volume and grip force were measured in each subject. RESULTS: Hand tremor frequency (mean 7.7 Hz) was reduced significantly by added inertia (mean 5.2 Hz) and it was negatively correlated with hand volume while there was no correlation with grip force. Finger tremor showed, subject to the arm position, maximally 3 and at least two distinct frequency bands (1-4, 6-11 and 15-30 Hz) reflecting the resonance frequencies of the whole arm, the hand and the finger, respectively. A significant EMG peak was found in 50-80% of the recordings. This EMG synchronization gave rise to a corresponding accelerometer peak or a significant EMG-EMG coherence in about one-third of the population indicating a central component of PT because its frequency was unaffected by mechanical changes in the periphery. We did not find a significant influence of age on the tremor frequency, while the sex of the subjects slightly but significantly changed the frequency range of hand tremor. Multiple partial correlations revealed, however, that the only direct influence on hand tremor frequency is the hand volume indicating that the influence of sex on hand tremor frequency is an indirect effect produced by the significantly larger hands of male subjects. CONCLUSIONS: In conclusion, the main determinants of PT are the mechanical properties of the oscillating limb. Apart from the dominating peripheral resonance mechanism we found indications of an additional central component of PT in about one-third of the normal population. There was no age dependence of tremor frequency and it was shown that the influence of the subjects' sex on tremor frequency only represents an indirect mechanical effect.

Adult↗
PubMed1994

Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells.

During procedures for parkinsonian tremor, neurons in the thalamic ventral nuclear group show periodic activity at tremor frequency (tremor-frequency activity). The tremor-frequency activity of some cells is significantly correlated with tremor. Cells in this region also display functional properties defined by activity related to somatosensory stimuli and to active movement. Cells with activity related to somatosensory stimulation were termed sensory cells while those with activity related to active movement were termed voluntary cells. Cells with activity related to both somatosensory stimulation and active movement were termed combined cells. Those with activity related to neither somatosensory stimulation nor active movement were termed no-response cells. Combined, voluntary and no-response cells were located in the region of thalamus where a lesion stops tremor and anterior to the region where sensory cells were found. Spectral cross-correlation analysis demonstrated that many combined, voluntary and no-response cells had a peak of activity at tremor frequency which was significantly correlated with electromyogram (EMG). Analysis of the phase of thalamic activity relative to EMG activity indicated that voluntary and combined cell activity usually led EMG during tremor. These results suggest that thalamic cells unresponsive to somatosensory stimulation (voluntary and no-response cells) and those responsive to somatosensory stimulation (combined cells) are involved in the mechanism of parkinsonian tremor. The activity of sensory cells frequently lagged behind tremor while activity of combined cells often led tremor. This finding suggests that the activity of these two cell types, both responding to sensory input, is related to tremor by different mechanisms.

Electromyography↗
PubMed1999

Using frequency domain characteristics to discriminate physiologic and parkinsonian tremors.

The manner in which characteristics of time series in the frequency domain can enhance discrimination between physiologic and parkinsonian tremor when tremor amplitude is low was examined. Rest tremor and postural tremor with and without visual feedback were recorded twice in the two hands of a group of patients with Parkinson's disease (PD) (n = 21) and a group of healthy control subjects (n = 30) using displacement laser systems. Recordings were analyzed quantitatively using amplitude and seven frequency domain characteristics. Postural tremor with no visual feedback allowed the most efficient discrimination between the two groups of subjects especially in velocity and acceleration (derived from displacement) and allowed identification of more patients with PD as separate from the range observed in the control group. Moreover, the frequency domain characteristics that were investigated identified the majority of the patients even when amplitude did not. After eliminating redundant (correlated) characteristics, it was found that the frequency composition of tremor in PD can be described adequately with four characteristics, which are the most reliable, independent, and discriminative elements for detecting early or subtle modifications in tremor. Also, a series of finger flexions was found to enhance physiologic tremor but not tremor in PD. Discrimination of low-amplitude tremor in PD from normal physiologic tremor is enhanced by examining the median frequency of oscillations, the concentration of power in the power spectrum, and the distribution of power in particular ranges. Tremor measurement should not be limited to acceleration data as some information is more visible in velocity time series.

Acceleration↗
PubMed2006

Development and validation of the vocal tremor scoring system.

BACKGROUND: Essential tremor (ET) occurs in approximately 4% of the population, and 25% of patients with ET have vocal tract involvement referred to as essential tremor of voice (ETV). Treatment of vocal tremor has a variable success rate most likely as a result of inaccurate identification of the affected area(s). A vocal tremor assessment system was developed to standardize the evaluation and scaling of vocal tremor. Applying this system clinically can help determine who will benefit most from botulinum toxin injection treatment. The Vocal Tremor Scoring System (VTSS) can also be used as a tool to determine treatment efficiency for all treatment modalities of ETV, including surgery, medications, and implantable devices. STUDY DESIGN: The authors studied instrument development and validation. METHODS: A clinical consensus conference was conducted to develop an assessment tool for standardized rating of vocal tremor location and severity. The assessment tool was then tested for reliability using video-perceptual analysis. Once validated, the assessment tool was applied to 10 examinations of patients with vocal tremor who had been treated with botulinum toxin A (BtxA) injections of the thyroarytenoid muscle(s) to determine the ability of the scoring instrument to predict treatment outcome. RESULTS: : The VTSS is based on severity scores for different anatomic sites within the vocal tract. The assessment areas of the VTSS are the palate, base of tongue, pharyngeal walls, larynx, supraglottis, and true vocal cords. Statistical analysis of the video-perceptual analysis results showed that the anatomic sites with the best interrater agreement were the true vocal folds, palate, base of tongue, and supraglottis. Overall, the VTSS demonstrated a level of interrater reliability of at least 0.914 at all sites. Intrarater reliability was excellent. The consensus group also analyzed 10 standardized examinations and the scores from both reviewer groups were then compared and found to have a reliability of at least 0.6 at each site. Pretreatment VTSS scores of 10 patients with ETV who underwent BtxA therapy were then compared with treatment response. The VTSS predicted the favorable treatment outcome 100% of the time when the score given to the true vocal folds was equal or greater to the mean of the scores given to the other sites. CONCLUSION: The VTSS represents the first standardized system for rating anatomic site(s) and severity of vocal tremor. This tool will allow improved communication between otolaryngologists, facilitate research in vocal tremor treatments, and establish a descriptive system for assessing vocal tremor. Using this assessment tool for patients with vocal tremor increases optimal patient selection and success rate for intralaryngeal botulinum toxin treatment.

Aged↗
PubMed1985

Harmine-, LON-954- and 5-hydroxytryptophan-induced tremors in rats withdrawn from ethanol.

The tremors induced by harmine, LON-954 (N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride) and 5-hydroxytryptophan (5-HTP) were studied in control rats and in rats withdrawn for 16-48 hrs from 6 to 9 days' ethanol administration. The frequencies and the intensities of the tremors were determined electronically. In control rats the frequency spectra of the tremors induced by harmine (20 mg/kg) and LON-954 (10 mg/kg) showed a narrow peak frequency at about 10 Hz. Atropine (1.2 mg/kg) altered neither the frequency nor the intensity of these tremors. 5-HTP (50 mg/kg) when given 3.5 hrs after iproniazid (100 mg/kg) induced tremor with peak frequencies at 6-7 Hz and 12 Hz. In ethanol-withdrawn rats treated with harmine or LON-954 the frequency analysis of tremor revealed a narrow peak frequency at about 12 Hz, which was neither the characteristic frequency of ethanol withdrawal tremor (6 Hz) nor that of harmine or LON-954 (10 Hz). The intensity of both harmine- and LON-954-induced tremor was significantly increased in ethanol-withdrawn rats. The ethanol-withdrawn rats were markedly sensitized to the effect of iproniazid+ 5-HTP, shown by deaths. The peak frequencies of this tremor were the same as those in control rats. The results suggest that harmine-induced tremor involves a dopaminergic-5-HT'ergic imbalance and the tremor induced by LON-954 a dopaminergic-cholinergic imbalance in the brain. The tremor in ethanol-withdrawn rats seems to be mediated by alterations in the activity of the cerebral 5-HT'ergic system.

5-Hydroxytryptophan↗