Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we examined whether activation of 5-HT1A receptors elicits antinociception in response to acute noxious chemical, thermal and mechanical stimuli in mice. In the writhing test, both agonists (e.g., 8-OH-DPAT, S 14671 and WY 50,324) and partial agonists (e.g., buspirone and gepirone) elicited a pronounced antinociception. However, antagonists (e.g., (-)-alprenolol and WAY 100,135) also induced antinociception and, at lower (inactive) doses, failed to modify the action of agonists. In addition, the separation between doses required for induction of antinociception as compared to those required for induction of ataxia (in the rotarod test) was variable and low for both agonists (median: 1.9) and partial agonists (median: 1.3), although it was somewhat greater for antagonists (> or = 3.3). In the hot-plate test, only certain agonists (e.g., 8-OH-DPAT) and partial agonists (e.g., gepirone) elicited antinociception and their actions were not attenuated by 5-HT1A antagonists which, themselves, were inactive in this paradigm. The 5-HT1C/2 antagonist, ritanserin, the 5-HT3 antagonist, ondansetron, the dopamine D2 receptor antagonist, raclopride, and the alpha 1-adrenoceptor antagonist, prazosin, were also ineffective in modifying the antinociception evoked by 5-HT1A agonists and partial agonists in the hot-plate test. In contrast, their actions were strongly attenuated by the alpha 2-adrenoceptor antagonist, idazoxan. In the tail-flick tests to noxious heat and noxious pressure, 5-HT1A receptor agonists, partial agonists and antagonists generally failed to induce antinociception. Moreover, modulation of stimulus intensity (from very weak to very intense) did not reveal any influence upon the latency to respond. In conclusion, in the writhing test, the data provide no evidence for a specific antinociceptive effect of the activation of 5-HT1A receptors. Further, in the hot-plate test, for those 5-HT1A agonists and partial agonists which induce antinociception, alpha 2-adrenoceptors rather than 5-HT1A receptors are implicated in their actions. Finally, in reflexive tests, irrespective of stimulus quality or intensity, 5-HT1A agonists and partial agonists do not mediate antinociception. These data suggest that the activation of 5-HT1A receptors does not, under these conditions of acute noxious stimulation, elicit antinociception.
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PMID:Serotonin and pain: evidence that activation of 5-HT1A receptors does not elicit antinociception against noxious thermal, mechanical and chemical stimuli in mice. 797 Aug 39

Interpretation of studies using single gene mutants is complicated by possible epistatic interactions with genetic background. Dopamine D2 receptor (Drd2) knockout mice on a C57BL/6 (B6) background show decreased basal locomotion, ethanol preference and ethanol-induced ataxia. Epistatic interactions were studied by examining the effect of this null mutation on several traits on a B6 or 129S6 x 129S2 (129) background. Modification of the null mutant effect on ethanol preference by ethanol-induced locomotor sensitization was also examined in B6 background mice. B6 knockout mice exhibited enhanced ethanol-induced locomotor stimulation and sensitization. The reduced ethanol consumption observed in ethanol-naive B6 Drd2 knockout mice was absent in ethanol-sensitized knockout mice. Ethanol-induced locomotor stimulation was not enhanced in 129 knockout mice, and locomotor sensitization was only modestly increased. However, 129 null mutant mice exhibited reduced basal locomotion and diminished ethanol-induced ataxia, similar to our previous results in B6 mice. The impact of the Drd2 null mutation on a subset of ethanol-related behavioral traits is subject to epistatic influences.
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PMID:Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis. 1283 20

We present single photon emission computed tomography (SPECT) studies using 123IFP-CIT (DAT scan) and 123I-IBZM imaging, performed on four members of a family with genetically proven spinocerebellar ataxia type 3 (SCA-3). DAT scan showed significant asymmetric decreased binding in the striatum in the two members with predominant parkinsonian phenotype, with mild and symmetric decreased binding in the member with the cerebellar phenotype, and normal in the asymptomatic member. The IBZM SPECT studies showed mild and asymmetrical reduction of the striatal dopamine D2 receptor density (parkinsonian members). SCA-3 can present with a levodopa responsive parkinsonism phenotype, and an abnormal DAT scan showing predominant impairment of presynaptic dopamine function.
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PMID:Striatal dopamine function in a family with multiple SCA-3 phenotypes. 2080 46

Most movement disorders in psychiatric patients are induced by neuroleptic antipsychotic medications, all of which are dopamine D2 receptor blocking drugs. These include: acute onset disorders: dystonic reactions, akathisia and the neuroleptic malignant syndrome (NMS); non-acute onset parkinsonism; and the tardive syndromes. However, many other medications, when used at recommended doses, also induce movement disorders, with tremor being the most common. With the exception of serotonin syndrome, they are rarely as severe or disabling as the neuroleptic extrapyramidal syndromes may be. The serotonin reuptake inhibiting (SSRI) drugs are associated with the serotonin syndrome, a life-threatening disorder, but may also cause tremor and akathisia. While SSRI's have been thought to occasionally cause a tardive dyskinesia-like syndrome, this almost never occurs without prior or concurrent neuroleptic exposure as well. There also are few reliable data to support an association between antidepressants and parkinsonism. Valproic acid has been shown to cause parkinsonism, and lithium may as well, in addition to both having the well-known side effect of tremors. Myoclonus and asterixis are usually induced by toxic levels of medications but may appear with therapeutic levels, particularly with anticonvulsant mood stabilizers, and clozapine. Ataxia rarely occurs with non-toxic levels of drug, particularly anticonvulsants, benzodiazepines and lithium.
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PMID:Movement disorders induced by psychiatric drugs that do not block dopamine receptors. 3287 38