Tremor In Rats Research Articles

Chlordecone-induced tremor: Quantification and pharmacological analysis

A procedure based on spectral analysis of whole body movements was developed to quantify chlordecone-induced tremor in rats. Male, Fischer-344 rats were given single or repeated ip doses of chlordecone, and whole body tremor was measured at 2.5-Hz intervals from 2.5 to 20 Hz. The most prevalent frequency and associated magnitude were recorded. Spectral analysis of the tremor produced by single doses of chlordecone could be differentiated from the spectral analysis of movement produced by various doses of harmine (5 to 20 mg/kg, ip) and apomorphine (0.5 to 2 mg/kg ip). The administration of 10 to 100 mg/kg chlordecone produced measurable tremor at 1, 5, 12, and 24 hr postdosing. The peak effect of chlordecone on tremor occurred at 12 hr postdosing. The most prevalent frequency of chlordecone-induced tremor was approximately 12 Hz following 50 to 100 mg/kg, 5 to 24 hr postdosing. Tremor was also quantified in rats receiving 5 to 10 mg/kg chlordecone daily for 10 consecutive days. Twenty-four hr after the last dose of chlordecone, spectral analysis indicated a peak frequency that was approximately the same as that obtained following acute administration of higher doses (≅12 Hz). Subsequent experiments with trihexyphenidyl and pizotifen suggested that the tremor produced by chlordecone might have a cholinergic and serotonergic component.

Decreased 3H-L-quinuclidinyl benzilate binding and muscarine receptor subsensitivity after chronic gamma-butyrolactone treatment.

A significant decrease in the number of 3H-quinuclidinyl benzilate (3H-QNB) binding sites in striatal membranes was observed in rats exposed to gamma-butyrolactone (GBL) during 3 weeks. This decrease in 3H-QNB binding was not due to a direct effect of GBL on muscarine receptors since no alterations of binding were produced by high concentrations of GBL or of its active metabolite gammahydroxybutyric acid (GHB) when added in vitro. Challenge doses of pilocarpine were less effective in producing catalepsy and tremors in rats chronically treated with GBL. It is proposed that the partial inhibition of the nigro-striatal dopaminergic pathway produced by chronic GBL treatment leads to a persistent activation of the intrastriatal cholinergic interneurons, which are tonically inhibited by dopaminergic nigrostriatal neurons. The activation of striatal cholinergic interneurons results in a decreased number of muscarine receptors and in a lower sensitivity to cholinomimetic agents. Moreover, tolerance to the anesthetic effect of GBL was found to occur after chronic treatment with this drug. The brain levels of GHB at the time of regaining of the righting reflex were 50% higher in GBL pretreated animals then in controls. Indicating the tolerance to GBL-induced "sleep" is due to a decrease sensitivity of the effector to GHB rather than to a faster inactivation of elimination of the drug.

Quantification of tremor in rats induced by physostigmine.

A simple and accurate device for recording tremor intensity in unanaesthetized and unrestrained rats is described. The physical measures of tremor are shown to have several advantages over previous devices. First, the new apparatus, unlike some earlier ones, does not restrict the animal's movements to an unusually small cage, with weighty mechanical devices or with electrical leads. Second, most earlier methods for measuring tremor use a subjective rating scale. However, the present method uses objective and reliable measures. In a double-blind, illustrative experiment involving complete crossover, Wistar rats were randomly injected IP with physostigmine in doses of 0.2, 0.4, 0.6 and 0.8 mg/kg or the corresponding amount of 0.9% NaCl solution as control. The recorded tremor intensity showed a clear dose-response relationship for physostigmine. Moreover, linear regression of the dose-response relationship showed that tremor intensity increased linearly with increasing doses of physostigmine. The cholinergic antagonist atropine (0.3 mg/kg SC) antagonized physostigmine-induced tremor, whereas methylatropine (0.3 mg/kg SC) tended to potentiate it. These results show that the technique described is suitable for quantification of tremor intensity in rats and for testing drug interactions on physostigmine-induced tremor.

Central cholinergic mechanisms in electrical self-stimulation and in drug-induced tremor in rats

Oxotremorine, a specific stimulant of central muscarinic acetylcholine receptors, inhibited lateral hypothalamic self-stimulation at a dose-level less than one-tenth of the necessary to produce body tremor. Tremor induced by oxotremorine (0.5 mg/kg) was inhibited by pretreatment with hyoscine (scopolamine) (0.3 mg/kg) or propranolol (20 mg/kg) but not by methylhyoscine (0.3 mg/kg) or apomorphine (0.3 mg/kg). Inhibition of self-stimulation by oxotremorine (.03 mg/kg) was prevented by hyoscine (0.3 mg/kg) but not by any other of the drugs tested and thus constitutes a uniquely specific in vivo model for assessing central antimuscarinic activity. The results confirm the presence of centrally situated ACh receptors eleciting tremor and inhibiting self-stimulation but provide no evidence of an effect on tremor by central adrenergic β-receptors.

Effects of diethylcholine in two animal models of Parkinsonism tremors

(2-Hydroxyethyl) methyldiethylammonium iodide (diethylcholine; DEC) was tested against trihexyphenidyl for its ability to block tremors in two animal models of Parkinsonism tremors. Both DEC (75 mg/kg) and trihexyphenidyl (10 mg/kg) antagonized physostigmine tremors in mice. Both drugs also blocked tremors in rats which received intracaudate injections of carbachol. DEC was more efficacious than trihexyphenidyl in the rat model. No dose-related inhibition of tremors was seen for trihexyphenidyl (5–20 mg/kg) but inhibition by DEC was dose-related (25–50 mg/kg). The ED 50 for tremor inhibition in the rat model by DEC was 33 mg/kg. DEC was also shown to cross the blood—brain barrier in mice. The probable mechanism of action of DEC is discussed.

Effect of administration route on DDT on acute toxicity and on drug biotransformation in various rodents.

DDT was administered to the guinea pig, mouse and rat either ig or ip and to the hamster ig in order to investigate variations in the response of hepatic and duodenal drug-metabolizing enzymes to DDT. The intragastric dose (160 mg/kg) was found to produce gastric bleeding and severe tremor in rats and mice but not in other rodents. The hepatic aryl hydrocarbon hydroxylase activity and cytochrome P-450 concentration decreased after the ig administration of DDT to rats, mice and guinea pigs but in hamsters the activiy of aryl hydrocarbon hydroxylase and cytochrome P-450 concentration increased 12 hr after the dosage. The aryl hydrocarbon hydroxylase activity decreased also in the duodenal mucosa of the rat after the ig administration of DDT. The ip dose had no effects on the hepatic or duodenal monooxygenase system in 12 hr. The UDPglucuronosyltransferase activity was slightly lowered in hepatic microsomes of the rat and mouse after the ig dose of DDT, but the decrease was more profound when measured after in vitro trypsin digestion of microsomes. The trypsin digestion activated the hepatic UDPglucuronosyltransferase in all the species studied, i.e., guinea pig, hamster, mouse and rat (3-, 3-, 5-, and 8-fold, respectively). The duodenal UDPglucuronosyltransferase activity was not affected by DDT administration in any of the species studied. The results suggest that the acute toxic effects of DDT are species-dependent and the administration route is important in DDT toxicity. The hydroxylation step in drug metabolism is more sensitive to DDT than the glucuronidation step.

The relationship between brain levels of cismethrin and bioresmethrin in female rats and neurotoxic effects

The oral toxicity of 5-benzyl-3-furylmethyl-(1R, cis)-chrysanthemate (cismethrin) to female rats decreased as their environmental temperature was raised. Acute oral LD 50 values increased from 157 mg/kg at 4°C to 197 mg/kg at 20°C and to > 1000 mg/kg at 30°C. Cismethrin was much more toxic given intravenously when the LD 50 was 4.5 mg/kg. This value did not change at different environmental temperatures. Irrespective of the environmental temperature, or route of adminstration, following the respective LD 50's cismethrin caused tremors in rats when brain levels of 0.5–1.0 μg/g were reached and, at death, brain concentrations were 3.9–5.1 μg/g. These results suggested that the accumulation of cismethrin by the brain could be used as a model for the nervous system as a whole. The isomeric 5-benzyl-3-furylmethyl-(1R, trans)-chrysanthemate (bioresmethrin) was about 50 times less toxic to rats than cismethrin. After an intravenous LD 50, tremors started when brain concentrations were 4–5 μg/g. At death, brain levels were 25–35 μg/g. Plasma esterases were about equally active in hydrolysing cismethrin and bioresmethrin, whereas liver microsomal esterases hydrolyzed bioresmethrin over 10 times more rapidly than cismethrin. It is suggested that the lower toxicity of bioresmethrin is not only due to its faster metabolism but to an intrinsically lower toxicity at the critical site of action in the nervous system.

Antimuscarinic drugs—Effect on brain acetylcholine and tremors in rats

The effect of cholinergic and antimuscarinic drugs on rat brain acetylcholine (ACh) concentration and on tremors has been studied. The cholinergic drugs (physotigmine and oxotremorine) increased brain ACh concentration and produced tremors. Antimuscarinic drugs (atropine, benztropine and trihexyphenidyl) decreased brain ACh concentration, blocked oxotremorine-induced tremors and prevented the oxotremorine- induced increase in brain ACh. Physostigmine-induced tremors and elevation in brain ACh concentration were not altered by pretreatment with benztropine and trihexyphenidyl. However, atropine reduced physostigmine-induced tremors and prevented the increase in brain ACh concentration. The results suggest that oxotremorine- and physostigmine-induced tremors are causally related to an increase in brain ACh concentration.

Effects of chloralose-urethan anesthesia on temperature regulation in dogs.

ArticleEffects of chloralose-urethan anesthesia on temperature regulation in dogs.F R Sharp, and H T HammelF R Sharp, and H T HammelPublished Online:01 Aug 1972https://doi.org/10.1152/jappl.1972.33.2.229MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySpecialized techniquesReferencesBibliographyBibliographyAppropriate thermal manipulations eliminate tremors in rats recovering from halothane anesthesiaD. A. Grahn, M. C. Heller, J. E. Larkin, and H. C. Heller1 December 1996 | Journal of Applied Physiology, Vol. 81, No. 6ReferencesThermogenetic response to mild hypothermia in anaesthetized infants and childrenPediatric Anesthesia, Vol. 2, No. 1Heart rate and blood pressure changes during radiofrequency irradiation and environmental heatingComparative Biochemistry and Physiology Part A: Physiology, Vol. 101, No. 1Local vascular effects of isoflurane during regional intestinal hypothermia in catsActa Anaesthesiologica Scandinavica, Vol. 35, No. 6Effects of 2.8-GHz microwaves on restrained and ketamine-anesthetized ratsRadiation and Environmental Biophysics, Vol. 28, No. 2Changes in body temperature after administration of antipyretics, LSD, Δ9-THC, CNS depressants and stimulants, hormones, inorganic ions, gases, 2,4-DNP and miscellaneous agentsNeuroscience & Biobehavioral Reviews, Vol. 5, No. 1 More from this issue > Volume 33Issue 2August 1972Pages 229-33 https://doi.org/10.1152/jappl.1972.33.2.229PubMed5054430History Published online 1 August 1972 Published in print 1 August 1972 Metrics

The influence of intracranially injected bradykinin on rest and intentional tremor in rat

The influence of intracranially injected bradykinin on rest and intentional tremor in rat

Mescaline and other O-methylated β-phenylethylamines: Intrastriatal induction of tremor in rats

A series of O-methylated β-phenylethylamines injected into the neostriatum of awake and freely moving rats produced motor dysfunction characterized by chewing motions, sialorrhea, adversive head turning, forelimb tremor and hyperextension of the trunk. These motor phenomena were similar in character to those induced by cholinergic stimulation of the striatum, but had significantly longer latency periods and duration. The latter differences suggest an indirect route of stimulation by the O-methylated amines.

A simple method for recording tremors in small animals.

ArticleA simple method for recording tremors in small animals.R E Dill, H L Dorman, and W M NickeyR E Dill, H L Dorman, and W M NickeyPublished Online:01 Apr 1968https://doi.org/10.1152/jappl.1968.24.4.598MoreSectionsPDF (468 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat "A simple method for recording tremors in small animals.." Journal of Applied Physiology, 24(4), pp. 598–599 Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByObjective detection of microtremors in netrin-G2 knockout miceJournal of Neuroscience Methods, Vol. 351Validation of a new computerized system for recording and analysing drug-induced tremor in ratsJournal of Pharmacological and Toxicological Methods, Vol. 46, No. 3Differential expression of c-Fos following administration of two tremorgenic agentsNeuroReport, Vol. 11, No. 11Animal models of tremor1 January 2001 | Movement Disorders, Vol. 14, No. 4A System for Measuring Tremor Intensity in RatsIEEE Transactions on Biomedical Engineering, Vol. BME-32, No. 8Quantification of tremor in rats induced by physostigminePsychopharmacology, Vol. 74, No. 3A rat model of resting tremorJournal of Pharmacological Methods, Vol. 2, No. 3Effects of acute and chronic injections of carbachol in the rat caudate nucleusNeuropharmacology, Vol. 18, No. 3Cholinergic stimulation of the caudate nucleus in rats: A model of Parkinson's diseaseNeuropharmacology, Vol. 17, No. 10Induction and Measurement of Tremor and Other DyskinesiasInduction of tremor in hypoxic gerbils by re-entry into a normoxic environmentExperimental Neurology, Vol. 53, No. 1Trunk rigidity and limb hypotonia produced in squirrel monkeys by direct cholinergic stimulation of the globus pallidusExperimental Neurology, Vol. 42, No. 35 The Pharmacotherapy of ParkinsonismChemical stimulation of discrete brain loci as a method of producing dyskinesia models in primatesExperimental Neurology, Vol. 34, No. 2Dentatectomy: Absence of effects on dyskinesias arizing from chemical stimulation of the striatum in ratsExperientia, Vol. 28, No. 1Drug effects on discriminative motor controlPhysiology & Behavior, Vol. 4, No. 3Mescaline and other O-methylated β-phenylethylamines: Intrastriatal induction of tremor in ratsBrain Research, Vol. 13, No. 2 More from this issue > Volume 24Issue 4April 1968Pages 598-9 https://doi.org/10.1152/jappl.1968.24.4.598PubMed5643413History Published online 1 April 1968 Published in print 1 April 1968 Metrics