Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both normal and genetically dystonic (dt) rats show a high-frequency forepaw tremor in response to systemic administration of the serotonin (5-HT) agonist quipazine at 8 days of age. The response declines with age in normal, but not dystonic, rats. By 16 days of age and after the development of a generalized movement disorder, the dystonic rat exhibits enhanced sensitivity to the tremorogenic effects of the drug in comparison with normal rats. Tremor was blocked by pretreatment with ketanserin, suggesting that it is mediated by 5-HT2 receptors. The dystonic rat has previously been shown to be insensitive to the tremorogenic effects of harmaline, a drug presumed to act indirectly through serotonergic neurons. This finding, coupled with the increased sensitivity to quipazine, suggests the presence of an abnormality in serotonergic systems in the mutants. Since there is evidence of abnormality in the olivo-cerebellar system in the dystonic rat, the alternative hypothesis that a nonserotonergic defect in the olivo-cerebellar system accounts for both the failure of behavioral response to harmaline and the persistent expression of a response to quipazine is also discussed.
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PMID:Enhanced sensitivity to quipazine in the genetically dystonic rat (dt). 226 55

Studies were performed to bring out a serotoninergic involvement in physostigmine tremor, hitherto known to be working via the cholinergic system. 5-Hydroxytryptamine (5-HT) was estimated fluorimetrically after isolation on Sephadex G-10 and acetylcholinesterase (AChE) was assayed spectrophotometrically. The dose-dependent tremor was quantified by a double-blind study. No correlation (r = 0.01) existed between tremor and AChE inhibition since the non-tremoring dose of physostigmine caused the same degree of enzyme inhibition. An increase of 5-HT was found to be correlated (r = 0.59) with the duration and intensity of tremor. Cholinergic antagonists atropine (2 and 5 mg/kg, i.p.), scopolamine (0.5, 1.0, 2.0 mg/kg, i.p.) and mecamylamine (1 mg/kg, i.p.) failed to block the tremor while the 5-HT antagonists methysergide (5 mg/kg, i.v.) and cyproheptadine (10 and 30 mg/kg, s.c.) could afford more than 60% protection. These results suggest a serotoninergic rather than a cholinergic component in the genesis of physostigmine tremor.
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PMID:Tremorogenesis by physostigmine is unrelated to acetylcholinesterase inhibition: evidence for serotoninergic involvement. 229

Serotonin receptors were examined in various brain regions of female rats 24 hours after treatment with 25, 50 or 75 mg/kg chlordecone. With each dose of chlordecone, there was a significant reduction in the specific binding of 3H-5-HT to striatum. Binding to cortex, hippocampus, hypothalamus, midbrain or brainstem did not systematically vary as a function of treatment conditions. Tremor developed in chlordecone treated female rats in a dose dependent manner with 25 mg/kg producing only slight tremor. Moderate to severe tremor was evident in rats given 75 mg/kg chlordecone. These findings support previous indications that chlordecone's action on the striatal serotoninergic system in an important component in its induction of tremor. Most such studies, however, have used relatively high doses of chlordecone so it has been difficult to determine if the serotoninergic change preceded or resulted from the tremor. The significant decrease in serotonin receptors at a dose of chlordecone which led to only slight tremor suggest that the serotoninergic change may be causally related to the production of the tremor.
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PMID:Serotonin receptors in striatum after chlordecone treatment of adult female rats. 242 36

In studying the role of serotonin (5-HT) in the mechanism of action of benzodiazepine (BDZ)-induced wet-dog shakes (WDS), only certain 1,4-substituted BDZ agonists were found to induce WDS at doses up to 60 mg/kg in the rat with the rank order of potency at peak dose effect clonazepam greater than nitrazepam = flunitrazepam much greater than nimetazepam = lorazepam. BDZs evoking WDS at lowest doses contained an R7 nitro group on the A ring. Non-BDZ agonists (CL 218,872), inverse agonists (beta-CCE), peripheral type receptor agonists (Ro 5-4864), and BDZ antagonists (Ro 15-1788) did not induce shaking behavior. Several 5-HT1 and 5-HT2 agonists and antagonists were tested as blockers, but only putative 5-HT1A agonists reduced WDS, 8-OH-DPAT and ipsapirone but not PAPP and 5-MeO-DMT having a significant effect. The effect of 8-OH-DPAT was dose dependent, with an ID50 of 0.86 mg/kg, but it was not reversed by 5-HT or adrenergic antagonists at the doses studied. Intracisternal 5,7-dihydroxytryptamine lesions did not alter frequency, latency, or time course of BDZ-induced WDS. BDZ-evoked WDS were enhanced by Ro 15-1788 (which inhibited ataxia) but were unaffected by the various types of BDZ agonists. Several BDZ agonists induced both WDS and ataxia, but ataxia was not blocked by serotonergic drugs. No significant correlation with ataxia, BDZ radioligand binding, antipentylenetetrazol activity, or other BDZ property was found. BDZ-evoked WDS may relate to the unique predominance of BDZ II and 5-HT1A receptors in the hippocampus, an important site for WDS, but 5-HT1A agonists appear to modulate WDS by opposing pharmacologic actions rather than by direct receptor antagonism. These data indicate a species difference in the shakes induced by BDZs in rats (5-HT2 independent) and in mice (5-HT2 related).
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PMID:Benzodiazepine-induced shaking behavior in the rat: structure-activity and relation to serotonin and benzodiazepine receptors. 254 77

Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5-HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences.
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PMID:Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5-hydroxytryptophan in the rat. 258 10

There have been few previous studies of the functional significance of 5,7-dihydroxytryptamine (5,7-DHT) lesions made in neonatal rats. To study the role of serotonin (5-HT) in recovery of function, rat pups and adult rats were injected intracisternally with 5,7-DHT or saline and challenged acutely with the 5-HT precursor 5-hydroxytryptophan (5-HTP) 4 weeks later as a test of behavioral supersensitivity. Compared to 5,7-DHT lesions in adults, neonatal lesions induced significantly greater 5-HT depletions in brainstem, but 5-HT depletions in other regions were not significantly different in the two groups. Rats with early 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP, consisting of all the component myoclonic-serotonergic behaviors seen in rats with 5,7-DHT lesions made as adults. However, there was significantly less 5-HTP-evoked head weaving, truncal myoclonus and shaking behavior in rats treated with 5,7-DHT as neonates. Body weight was reduced both in rats with early and late 5,7-DHT lesions, but reduction persisted in rats with early lesions. These data indicate overall similarity with some differences between neurochemical and behavioral effects of early and late 5,7-DHT lesions made by the intracisternal route. They suggest that recovery mechanisms did not occur or failed to reverse the neurochemical or behavioral consequences of early 5,7-DHT lesions.
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PMID:Intracisternal 5,7-dihydroxytryptamine lesions in neonatal and adult rats: comparison of response to 5-hydroxytryptophan. 278 68

Oral administration of 120 or 240 mg/kg permethrin produced dose- and time-related tremor in rats with the peak effect occurring 5 hrs after dosing. Subsequent experiments done 5 hrs postdosing found that 45 to 180 mg/kg permethrin produced dose-related increases in rectal temperature and enhanced responsiveness to an acoustic stimulus. Tremor was detected at 90 and 180 mg/kg. Neurochemical analyses of regional biogenic amines and their metabolites and amino acids 5 hrs after 90 or 180 mg/kg indicated that 5-HIAA levels were increased in the hypothalamus (HYP), brain stem (BS), hippocampus (HPC), and striatum (STR); 5-HT was not affected. MHPG was increased in the HYP and BS, while NE was decreased at the high dose only. DOPAC and HVA were increased in the STR after 90 and 180 mg/kg, while DA was not affected. Aspartate levels were increased in the BS and STR; glutamate was increased in the BS. Taurine, glutamine, glycine, and GABA were not affected. A time-course analysis of neurochemical changes 2, 5, 12, and 24 hrs postdosing indicated that 5 hrs was the time of peak effect for permethrin. Permethrin-induced tremor and hyperthermia were significantly correlated with dose- and time-related changes in MHPG, 5-HIAA, and ASP.
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PMID:Neurobehavioral effects of permethrin are associated with alterations in regional levels of biogenic amine metabolites and amino acid neurotransmitters. 287 38

The effect of beta-adrenoceptor antagonists, varying in lipophilicity and receptor selectivity, were studied on tremor elicited by L-5-hydroxytryptophan (L-5-HTP) in rats pretreated with a peripherally acting decarboxylase inhibitor and a monoamine oxidase inhibitor, or by the directly acting 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Plasma levels of the beta-adrenoceptor antagonists were determined simultaneously. The non-selective lipophilic adrenoceptor antagonist propranolol was found to dose-dependently reduce tremor intensity, whereas the non-selective hydrophilic adrenoceptor antagonist sotalol had no effect, indicating a central site of action. Furthermore, beta 1-selective blockade with the adrenoceptor antagonist metoprolol had no effect on tremor intensity, whereas the beta 2-selective antagonist ICI 118,551 dose-dependently suppressed tremor intensity, suggesting that the beta-adrenoceptor subtype involved is of the beta 2-type. These results suggest that blockade of centrally located beta 2-adrenoceptors are able to attenuate the tremor response following 5-hydroxytryptamine receptor activation.
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PMID:Blockade of central beta-adrenoceptors attenuates tremor induced by 5-hydroxytryptamine (5-HT)-receptor activation in rats. 288 12

Reciprocal forepaw treading, hindlimb abduction, and Straub tail are some of the abnormal motor behaviors of the classical 'serotonin syndrome,' which results from activation of serotonin (5-HT) receptors. However, we also observed them in the syndrome evoked by the alpha-adrenergic agonist clonidine, at high doses (5-40 mg/kg). Other features of the clonidine syndrome (scored from videotapes) were body and head tremor, forelimb hyperextension, ataxia, vertical jumping, tactile hyperreactivity, and autonomic signs (piloerection, pupillary dilatation, salivation, proptosis). The clonidine syndrome persisted for several hours and was not lethal. Clonidine suppressed locomotor activity (photocell recording) and induced episodes of catalepsy and 5-HT-independent impairment of motor habituation. Single high doses of drugs active at several different neurotransmitter receptors significantly reduced total behavioral score through effects primarily on tremor and autonomic signs, but none prevented the clonidine syndrome. Lesions of monoaminergic neurons [intracisternal 5,7-dihydroxytryptamine (DHT) or 6-hydroxydopamine] or monoamine depletion by intraperitoneal reserpine all failed to prevent this motor syndrome. Co-administration of 5-HTP and clonidine did not exacerbate the clonidine syndrome in naive rats and did not prevent the onset of the serotonergic syndrome in rats with DHT lesions. These data suggest that neither catecholamines nor 5-HT have a major role in the serotonin-like behavioral responses to high doses of clonidine.
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PMID:High-dose clonidine motor syndrome: relationship to serotonin syndrome. 288 33

1. The relationship of the behavioral syndromes induced by the co-transmitters thyrotropin releasing hormone (TRH) and serotonin (5-HT) has not been previously studied with drugs selective for 5-HT receptor subtypes. 2. Both the TRH analog MK-771 (in naive rats) and 5-hydroxytryptophan (in rats with 5,7-dihydroxytryptamine [DHT] lesions) evoked reciprocal forepaw tapping, Straub tail, hunching, hindlimb abduction, and shaking behavior. Sniffing and rearing were features of the MK-771 but not the 5-HT syndrome. 3. 5-HTP potentiated MK-771-induced hyperthermia. 4. MK-771 evoked two types of shaking behavior, head shakes (HS) and wet-dog shakes (WDS). Neither independently was dose-related, unlike total shaking behaviors. 5. MK-771-induced shaking behavior was pharmacologically dissociated from other MK-771-evoked behaviors. A 5-HT1A agonist (8-OH-DPAT) blocked WDS, but like putative 5-HT1B (RU 24969) and 5-HT2 (DOI) agonists and the 5-HT antagonists methysergide (non-selective), ritanserin (5-HT2 selective), and l-propranolol (5-HT1 selective), it did not block other antagonists behavioural effects of MK-771. 6. Ipsapirone, a 5-HT1A-active drug purported both as an agonist and as an antagonist, inhibited MK-771-evoked WDS, like 8-OH-DPAT, but did not induce the serotonin syndrome, unlike 8-OH-DPAT. 7. DHT-treated rats were behaviorally supersensitive to 10 mg/kg MK-771 as indicated by a significantly shortened latency of onset of WDS and greater frequency of abnormal forepaw movements. The same rats were also supersensitive to 50 mg/kg 5-HTP to a significantly greater degree. 8. These data suggest behavioral relatedness of the TRH and 5-HT syndromes, but distinctive pharmacologic features and presumed mechanisms of action.
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PMID:The comparative pharmacology of the behavioral syndromes induced by TRH and by 5-HT in the rat. 289 33


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