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)

The influence of cholecystokinin (CCK), bilaterally injected into the rostral nucleus accumbens, on the EEG and behavioural effects induced by phencyclidine (PCP) has been studied in rats. CCK (10 ng) significantly inhibited PCP-induced EEG effects (increase of spectral power with respect to pre-drug tracing; increase of relative power distribution in the slowest frequency bands), and behavioural effects (circling and ataxia). The inhibitory effects of CCK were completely antagonized by 1 ng PD 135-158, a selective CCKB receptor antagonist, but not by lorglumide (1 microgram), a selective CCKA receptor antagonist. Since the effects induced by PCP in rodents have been proposed to be an experimental correlate of the psychotic symptoms it induces in humans, these results indicate that CCK may act as a neuroleptic. They also suggest that CCKB receptors located in the rostral nucleus accumbens may be involved in the neuroleptic-like activity of CCK.
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PMID:The stimulation of cholecystokinin receptors in the rostral nucleus accumbens significantly antagonizes the EEG and behavioural effects induced by phencyclidine in rats. 748 May 47

We studied the aggressive behaviour induced by repeated treatment with apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats. The first signs of defensive aggressiveness appeared on the third day of apomorphine treatment and were generally seen on the 7th day. Aggressiveness induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg i.p., dizocilpine even accelerated the appearance of apomorphine-induced aggressive behaviour, which manifested on the 3rd day in all rats. In a separate study, a 7-day treatment with dizocilpine (0.25-1 mg/kg i.p.) of rats, sensitized by a prior 10-day apomorphine treatment, did not reverse the established aggressive behaviour. The coadministration of apomorphine and cholecystokinin (CCK) -A or -B antagonists, devazepide or L-365,260 (0.01-2.5 mg/kg i.p.) respectively, neither affected development of apomorphine-induced aggressive behaviour nor intensity of aggressiveness in the sensitized rats. In binding studies neither density nor affinity of striatal dopamine D2 receptors was changed by acute or chronic apomorphine treatment. The number of [3H]pCCK-8 binding sites in the frontal cortex increased already after a single injection of apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats. 763 Apr 27

Changes in immunoreactive somatostatin (SOM) and cholecystokinin (CCK-8) levels in the cerebellum and cerebrum were investigated in three types of genetically-determined ataxic mutant mice: rolling mouse Nagoya (RMN), weaver, and Purkinje cell degeneration (PCD) mice. The cerebellar pathology in each of these types differs. The concentration of both SOM and CCK-8 (ng/mg weight) was significantly higher in the cerebellum and the cerebrum of the three types of ataxic mutant mice than in these regions in the respective controls. SOM and CCK-8 content (ng/organ) was significantly higher in PCD and RMN than in controls but this was not in the weaver mice. The possible involvement of both peptides in manifestations of ataxia is discussed.
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PMID:Levels of somatostatin and cholecystokinin in the brain of ataxic mutant mice. 810 Sep 81

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.
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PMID:Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum. 987 55

SCA1, a fatal neurodegenerative disorder, is caused by a CAG expansion encoding a polyglutamine stretch in the protein ATXN1. We used RNA sequencing to profile cerebellar gene expression in Pcp2-ATXN1[82Q] mice with ataxia and progressive pathology and Pcp2-ATXN1[30Q]D776 animals having ataxia in absence of Purkinje cell progressive pathology. Weighted Gene Coexpression Network Analysis of the cerebellar expression data revealed two gene networks that significantly correlated with disease and have an expression profile correlating with disease progression in ATXN1[82Q] Purkinje cells. The Magenta Module provides a signature of suppressed transcriptional programs reflecting disease progression in Purkinje cells, while the Lt Yellow Module reflects transcriptional programs activated in response to disease in Purkinje cells as well as other cerebellar cell types. Furthermore, we found that upregulation of cholecystokinin (Cck) and subsequent interaction with the Cck1 receptor likely underlies the lack of progressive Purkinje cell pathology in Pcp2-ATXN1[30Q]D776 mice.
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PMID:Cerebellar Transcriptome Profiles of ATXN1 Transgenic Mice Reveal SCA1 Disease Progression and Protection Pathways. 2694 90