INT26408

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Context Info
Confidence 0.18
First Reported 1989
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 36
Total Number 43
Disease Relevance 13.46
Pain Relevance 20.32

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

Anatomy Link Frequency
striatum 4
neuron 1
STN 1
muscle 1
brain 1
da (Mus musculus)
Pain Link Frequency Relevance Heat
Dopamine 6482 100.00 Very High Very High Very High
midbrain 209 99.98 Very High Very High Very High
antagonist 82 99.96 Very High Very High Very High
Opioid 4 99.74 Very High Very High Very High
narcan 3 99.30 Very High Very High Very High
addiction 91 99.18 Very High Very High Very High
nMDA receptor antagonist 35 98.48 Very High Very High Very High
Eae 160 96.88 Very High Very High Very High
Glutamate 84 95.96 Very High Very High Very High
Serotonin 101 95.56 Very High Very High Very High
Disease Link Frequency Relevance Heat
Parkinson's Disease 1392 99.84 Very High Very High Very High
Disease 704 99.84 Very High Very High Very High
Aging 120 99.40 Very High Very High Very High
Stress 120 98.54 Very High Very High Very High
Tremor 320 98.40 Very High Very High Very High
Neurologic Manifestations 32 97.40 Very High Very High Very High
Neurodegenerative Disease 112 97.28 Very High Very High Very High
Death 72 96.44 Very High Very High Very High
Pathologic Processes 64 95.96 Very High Very High Very High
Muscle Hypertonia 32 94.72 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Furthermore, a blockade of D1/D2 DA receptors was ineffective in preventing the locomotor stimulating action of (+)-MDMA.
Negative_regulation (blockade) of D2 DA associated with dopamine
1) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.15 Pain Relevance 0.61
Thus, in a normal animal, complete depletion of striatal DA is unachievable by TH inhibition alone, and additional depletion of vesicular DA by VMAT2 inhibitors, such as reserpine is required [33,47–49].
Negative_regulation (depletion) of DA associated with dopamine
2) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.22 Pain Relevance 0.63
MT is sufficient to induce profound depletion of DA [12,13,37].
Negative_regulation (depletion) of DA associated with dopamine
3) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.07 Pain Relevance 0.58
To explore this phenomenon in detail, we first measured the time-course of striatal DA depletion in DAT-KO and control mice following treatment with ?
Negative_regulation (depletion) of DA associated with dopamine
4) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.06 Pain Relevance 0.59
First, mice lacking the DAT display dramatically decreased (20-fold) striatal tissue DA content, that mostly represents intraneuronal DA concentrations.
Negative_regulation (decreased) of DA associated with dopamine
5) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.13 Pain Relevance 0.78
MT results only in a relatively slow and partial depletion of DA in brain tissues that is not sufficient for generation of PD-like symptoms [29,45,46].
Negative_regulation (depletion) of DA in brain associated with parkinson's disease and dopamine
6) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.32 Pain Relevance 0.57
Thus, in a normal animal, complete depletion of striatal DA is unachievable by TH inhibition alone, and additional depletion of vesicular DA by VMAT2 inhibitors, such as reserpine is required [33,47–49].
Negative_regulation (depletion) of DA associated with dopamine
7) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.22 Pain Relevance 0.65
Severe depletion of DA in ?
Negative_regulation (depletion) of DA associated with dopamine
8) Confidence 0.18 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.20 Pain Relevance 0.46
This selective depletion of DA in dopaminergic terminals of DAT-KO mice, as well as analogous depletion observed in mice lacking NET [51] or serotonin transporter [52] with NE and serotonin (5-HT), respectively, reflects the critical role of transporter-mediated recycling in the maintenance of intracellular storage pools [13].
Negative_regulation (depletion) of DA associated with dopamine and serotonin
9) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.15 Pain Relevance 0.70
However, in rodents, the prolonged absence of DA is not compatible with life [3,7,8], and animals with chronic severe DA depletion are generally not available for routine experimentation.
Negative_regulation (depletion) of DA associated with dopamine
10) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.53 Pain Relevance 0.57
A number of animal models of DA deficiency, based on pharmacologic, neurotoxic, or genetic approaches, have been developed to understand basic pathological processes leading to PD and/or to search for novel principles of therapy [29–36].
Negative_regulation (deficiency) of DA associated with parkinson's disease, pathologic processes and dopamine
11) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.78 Pain Relevance 0.44
Major motor manifestations of DA deficiency in PD include, but are not limited to, resting tremor (tremor occurring in the absence of voluntary movement), rigidity (tonically increased muscle tone), bradykinesia/akinesia (slowness/difficulty in initiating movement), gait disturbance and postural instability, facial masking, and decreased eye-blinking [18].
Negative_regulation (deficiency) of DA in muscle associated with tremor, parkinson's disease, muscle hypertonia, dopamine and hypokinesia
12) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.88 Pain Relevance 0.55
Other manifestations associated with DA deficiency as described in Figure 3 were also essentially completely reversed (data not shown).
Negative_regulation (deficiency) of DA associated with dopamine
13) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0 Pain Relevance 0.56
We, therefore, tested several non-dopaminergic compounds that potentially could reverse the consequences of severe DA deficiency in DDD mice (see Table 1).
Negative_regulation (deficiency) of DA associated with dopamine
14) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.26 Pain Relevance 0.47
Furthermore, several treatments, although not inducing forward locomotion per se, were, nevertheless, somewhat effective in reversing other manifestations of DA deficiency.
Negative_regulation (deficiency) of DA associated with dopamine
15) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.35 Pain Relevance 0.24
These models either recapitulate the loss of DA through pharmacologic or genetic manipulation, or recapitulate the neurodegenerative process through administration of selective neurotoxins and, recently, through mutations of specific proteins.
Negative_regulation (loss) of DA associated with dopamine and neurodegenerative disease
16) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.66 Pain Relevance 0.43
Although it is likely that the lack of locomotor effects of these drugs in DDD mice is related to an unprecedented level of DA depletion in these mice, it should be emphasized that in our studies only a few doses or combinations of drugs were tested.
Negative_regulation (depletion) of DA associated with dopamine
17) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.29 Pain Relevance 0.32
Furthermore, pharmacologic studies have shown that significant DA depletion may occur after administration of DAT inhibitors, particularly after chronic drug treatment [13].
Negative_regulation (depletion) of DA associated with dopamine
18) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.09 Pain Relevance 0.78
Thus, the lack of DA combined with the striking and highly reproducible behavioral phenotype in these mice can be used as an excellent tool to evaluate the potential of drugs that can affect locomotion in a DA-independent manner.
Negative_regulation (lack) of DA associated with dopamine
19) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.33 Pain Relevance 0.65
By using a combination of genetic and pharmacologic approaches we have developed a novel acute mouse model of severe DA deficiency, DDD mice.
Negative_regulation (deficiency) of DA associated with dopamine
20) Confidence 0.13 Published 2005 Journal PLoS Biology Section Body Doc Link PMC1181539 Disease Relevance 0.14 Pain Relevance 0.71

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