YM-14673, a thyrotropin-releasing hormone analogue, injected into the nucleus accumbens and the striatum produces repetitive jaw movements in rats

Miwa, Yasuhiro; Koshikawa, Noriaki; Miyata, Nobuo; Koshida, Yoko; Kobayashi, Masafumi; Cools, Alexander R.

doi:10.1016/0014-2999(95)00066-t

Cited by 7 publications

(4 citation statements)

References 36 publications

(27 reference statements)

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“…Particularly relevant to the findings we report here are experiments suggesting that the behavioral patterns stimulated by increased intrastriatal TRH in intact non-primate mammals are akin to human dyskinesia [57], [58], [59], [60], [61], [62], [63]. Studies have suggested that the behavioral effects of TRH are exerted via the stimulation of striatal dopamine release [64], and that they can be antagonized by both D1-class and D2-class dopamine receptor antagonists [57], [58], [59].…”

Section: Discussionsupporting

confidence: 54%

“…Studies have suggested that the behavioral effects of TRH are exerted via the stimulation of striatal dopamine release [64], and that they can be antagonized by both D1-class and D2-class dopamine receptor antagonists [57], [58], [59]. In turn, striatal dopamine levels have also been shown to modulate the release of TRH within the rat striatum [61], [62], with higher levels of dopamine correlating with higher levels of intrastriatal TRH.…”

Section: Discussionmentioning

confidence: 99%

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Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

et al. 2010

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BackgroundDyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition.Methodology/Principal FindingsQuantitative real-time polymerase chain reaction (PCR) was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH) was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes.Conclusions/SignificanceTRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

et al. 2010

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“…The beneficial effect maintained for as long as 8 h, which was in consistency with the long half-life of Taltirelin ( Kinoshita et al, 1998 ). Besides, animals exhibited involuntary shaking and repeated jaws action after the injection of Taltirelin above 5 mg/kg ( Supplementary video ), which may be related to the stimulation of 5-HT system ( Miwa et al, 1995 ) by Taltirelin during high dose use. We also examined and found that Taltirelin (>5 mg/kg) elevated serum level of TT3, TT4, FT3, and FT4 in PD rats (Supplementary Figure S5 ).…”

Section: Discussionmentioning

confidence: 99%

TRH Analog, Taltirelin Improves Motor Function of Hemi-PD Rats Without Inducing Dyskinesia via Sustained Dopamine Stimulating Effect

Zheng

Chen

Tan

et al. 2018

Front. Cell. Neurosci.

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Thyrotropin-releasing hormone (TRH) and its analogs are able to stimulate the release of the endogenic dopamine (DA) in the central nervous system. However, this effect has not been tested in the Parkinson’s disease (PD), which is characterized by the DA deficiency due to the dopaminergic neurons loss in the substantia nigra. Here, we investigated the therapeutic effect of Taltirelin, a long-acting TRH analog on 6-hydroxydopamine-lesioned hemi-Parkinsonian rat model. 1–10 mg/kg Taltirelin i.p. administration significantly improved the locomotor function and halted the electrophysiological abnormities of PD animals without inducing dyskinesia even with high-dose for 7 days treatment. Microdialysis showed that Taltirelin gently and persistently promoted DA release in the cortex and striatum, while L-DOPA induced a sharp rise of DA especially in the cortex. The DA-releasing effect of Taltirelin was alleviated by reserpine, vanoxerine (GBR12909) or AMPT, indicating a mechanism involving vesicular monoamine transporter-2 (VMAT-2), dopamine transporter (DAT) and tyrosine hydroxylase (TH). The in vivo and in vitro experiments further supported that Taltirelin affected the regulation of TH expression in striatal neurons, which was mediated by p-ERK1/2. Together, this study demonstrated that Taltirelin improved motor function of hemi-PD rats without inducing dyskinesia, thus supporting a further exploration of Taltirelin for PD treatment.

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“…It has also been shown that the nucleus accumbens play a role in jaw movements elicited by YM-14673 (1). Since the response to YM-14673 was attenuated by the dopamine D1/D2 receptor antagonist cis-(Z)-flupentixol (1), it is suggested that YM-14673 directly or indirectly enhanced the dopamine activity at the level of dopamine D1/D2 receptors.…”

Section: Drugsmentioning

confidence: 99%

Effects of YM-14673, a thyrotropin-releasing hormone analogue, injected into the shell and the core of the nucleus accumbens on production of repetitive jaw movements in rats: Comparison with the effects of a dopamine D1 and D2 receptor agonist combination.

Adachi

Hirose

Fujioka

et al. 1997

The Journal of Nihon University School of Dentistry

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YM-14673, a thyrotropin-releasing hormone analogue, injected into the nucleus accumbens and the striatum produces repetitive jaw movements in rats

Abstract: receptors may at least partly contribute to these effects. Anyhow, these mechanisms differ from that underlying the ability of YM-14673 and TRH to elicit wet-dog shakes, a mechanism that is known to involve serotonergic processes.

Cited by 7 publications

References 36 publications

Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

TRH Analog, Taltirelin Improves Motor Function of Hemi-PD Rats Without Inducing Dyskinesia via Sustained Dopamine Stimulating Effect

Effects of YM-14673, a thyrotropin-releasing hormone analogue, injected into the shell and the core of the nucleus accumbens on production of repetitive jaw movements in rats: Comparison with the effects of a dopamine D1 and D2 receptor agonist combination.

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