Validation of a new computerized system for recording and analysing drug-induced tremor in rats.

INTRODUCTION Certain drugs can induce tremor in small animals and can be used as Parkinson's disease or essential experimental tremor models. However, the use of arbitrary scales for evaluating tremor in experimental models is limited by observer subjectivity. Progress in electronics and computer science has allowed a more precise quantification of tremor. The objective of the present study was to validate a newly developed low-cost method of spectral registration and analysis of tremor in free-moving rats. METHODS Male Wistar rats, 3-4 months of age, previously placed for 5 min inside a sensor cage, were administered with different doses of eserine (0.25-1.5 mg/kg), oxotremorine (0.25-1.5 mg/kg) or harmaline (7.5-60 mg/kg). Drug-induced tremor was recorded during 10 min using a computerized system composed of force transducers, a signal conditioning circuit, a digitizing interface and a microcomputer. The signal transmitted to the computer was quantified, stored and analyzed for its amplitude and frequency by means of specific programs. RESULTS Tremor was induced with an amplitude that was dose-dependent for all drugs used. Tremor frequency was dose-dependent for oxotremorine and eserine, but not for harmaline. The performance of the system was compared with that of other systems described in behavioral instrumentation literature. DISCUSSION The present data indicate that the new system is capable of detecting the tremor induced by drugs, and that the programs used for spectral analysis allow the quantification of the amplitude and the frequency of the tremor in free-moving rats.

[1]  J. M. Spyers-Ashby,et al.  Classification of normal and pathological tremors using a multidimensional electromagnetic system. , 1999, Medical engineering & physics.

[2]  R. Pertwee,et al.  Cannabinoids control spasticity and tremor in a multiple sclerosis model , 2000, Nature.

[3]  S. Sarkar,et al.  Effects of serotoninergic drugs on tremor induced by physostigmine in rats , 2000, Behavioural Brain Research.

[4]  I. Kopin,et al.  The role of peripheral catecholamines in oxotremorine tremor in the rat and its antagonism by beta adrenoceptor blocking agents. , 1978, The Journal of pharmacology and experimental therapeutics.

[5]  Ricardo Santos,et al.  Triiodothyronine (T3) modifies cholinergic-induced hypothermia and tremor in rats , 1993, Pharmacology Biochemistry and Behavior.

[6]  J. Harvey,et al.  Harmaline competitively inhibits [ 3H ]MK-801 binding to the NMDA receptor in rabbit brain , 1997, Brain Research.

[7]  M. Gresty,et al.  A novel method of recording arm movements. A survey of common abnormalities. , 1981, Archives of neurology.

[8]  Guanghui Wang,et al.  Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine , 2001, Psychopharmacology.

[9]  F. W. Klussmann,et al.  Spectral analysis of tremorine and cold tremor electromyograms in animal species of different size , 1983, Pflügers Archiv.

[10]  J. Harvey,et al.  Harmaline-induced tremor and impairment of learning are both blocked by dizocilpine in the rabbit , 1997, Brain Research.

[11]  J. Dichgans,et al.  Wrist tremor: investigation of agonist-antagonist interaction by means of long-term EMG recording and cross-spectral analysis. , 1996, Electroencephalography and clinical neurophysiology.

[12]  P. Slater,et al.  Effects of lesioning basal ganglia nuclei and output pathways on tremorine-induced tremor in rats , 1982, Journal of the Neurological Sciences.

[13]  R. Llinás,et al.  Oscillatory properties of guinea‐pig inferior olivary neurones and their pharmacological modulation: an in vitro study. , 1986, The Journal of physiology.

[14]  A Beuter,et al.  Tremor in Cree subjects exposed to methylmercury: a preliminary study. , 1998, Neurotoxicology and teratology.

[15]  Y. Gomita,et al.  Involvement of 5-hydroxytryptamine(1A) receptors in nicotine-induced tail tremor in rats. , 2000, European journal of pharmacology.

[16]  J. Salamone,et al.  Tremulous Characteristics of the Vacuous Jaw Movements Induced by Pilocarpine and Ventrolateral Striatal Dopamine Depletions , 1997, Pharmacology Biochemistry and Behavior.

[17]  S. Fowler,et al.  A new rodent model for neuroleptic-induced pseudo-parkinsonism: low doses of haloperidol increase forelimb tremor in the rat. , 1990, Behavioral neuroscience.

[18]  J. Mcelhaney,et al.  A system to measure the forces and moments at the knee and hip during level walking , 1984, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[19]  Yen Hc,et al.  Evaluation of anti-tremor drugs in tremor-induced rodents. , 1965 .

[20]  Anthony Sances,et al.  Quantitative Evaluation of Long-Term Parkinson Tremor , 1977, IEEE Transactions on Biomedical Engineering.

[21]  Anne Beuter,et al.  The measurement of tremor using a velocity transducer: comparison to simultaneous recordings using transducers of displacement, acceleration and muscle activity , 1999, Journal of Neuroscience Methods.

[22]  H. Shinozaki,et al.  Modification of drug-induced tremor by systemic administration of kainic acid and quisqualic acid in mice , 1987, Neuropharmacology.

[23]  L Carlsson,et al.  Objective quantification of tremor in conscious unrestrained rats, exemplified with 5-hydroxytryptamine-mediated tremor. , 1985, Journal of pharmacological methods.

[24]  S. Fowler,et al.  A force-plate actometer for quantitating rodent behaviors: illustrative data on locomotion, rotation, spatial patterning, stereotypies, and tremor , 2001, Journal of Neuroscience Methods.

[25]  James D. Frost,et al.  Triaxial Vector Accelerometry: A Method for Quantifying Tremor and Ataxia , 1978, IEEE Transactions on Biomedical Engineering.

[26]  E. Carlini,et al.  Central responses to cholinergic drugs of REM sleep deprived rats , 1988, Pharmacology Biochemistry and Behavior.

[27]  O. Lippold Oscillation in the stretch reflex arc and the origin of the rhythmical, 8–12 c/s component of physiological tremor , 1970, The Journal of physiology.

[28]  R. Llinás,et al.  Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. , 1981, The Journal of physiology.

[29]  J. Clement,et al.  Device for quantitating tremor activity in mice: antitremor activity of atropine versus soman- and oxotremorine-induced tremors. , 1989, Journal of pharmacological methods.

[30]  A. Björklund,et al.  Morphological and functional studies on the serotoninergic innervation of the inferior olive. , 1981, Journal de physiologie.

[31]  H. L. Dorman,et al.  A simple method for recording tremors in small animals. , 1968, Journal of applied physiology.

[32]  J. Stanford,et al.  At low doses, harmaline increases forelimb tremor in the rat , 1998, Neuroscience Letters.