INT13989

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Context Info
Confidence 0.24
First Reported 1985
Last Reported 2011
Negated 2
Speculated 1
Reported most in Body
Documents 27
Total Number 31
Disease Relevance 5.34
Pain Relevance 16.76

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

transport (Slc3a1) plasma membrane (Slc3a1) carbohydrate metabolic process (Slc3a1)
Anatomy Link Frequency
brain 2
brainstem 2
nucleus accumbens 2
striatum 1
midbrain 1
Slc3a1 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Dopamine 985 100.00 Very High Very High Very High
Enkephalin 58 100.00 Very High Very High Very High
agonist 88 99.96 Very High Very High Very High
dopamine receptor 39 99.96 Very High Very High Very High
Glutamate 115 99.84 Very High Very High Very High
opioid receptor 20 99.80 Very High Very High Very High
mu opioid receptor 4 99.74 Very High Very High Very High
cocaine 21 99.68 Very High Very High Very High
withdrawal 12 99.36 Very High Very High Very High
Nucleus accumbens 22 99.12 Very High Very High Very High
Disease Link Frequency Relevance Heat
Targeted Disruption 17 99.52 Very High Very High Very High
Catalepsy 18 98.44 Very High Very High Very High
Attention Deficit Hyperactivity Disorder 19 98.36 Very High Very High Very High
Depression 182 96.28 Very High Very High Very High
Stress 27 94.92 High High
Bradycardia 3 93.16 High High
Increased Venous Pressure Under Development 32 91.48 High High
Recurrence 8 91.00 High High
Congenital Anomalies 2 87.92 High High
Neurodegenerative Disease 13 83.04 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
OBJECTIVES: The effect of blocking dopamine D1, D2, mu-opiate or delta-opiate receptors in the nucleus accumbens on the intravenous self-administration of combined heroin and cocaine was examined in rats.
Negative_regulation (blocking) of D2 in nucleus accumbens
1) Confidence 0.24 Published 2005 Journal Psychopharmacology (Berl.) Section Body Doc Link 15682301 Disease Relevance 0 Pain Relevance 0
Proenkephalin and the D2-receptor mRNAs were not altered during cocaine abstinence, though proenkephalin was elevated following acute but not repeated cocaine administration.
Neg (not) Negative_regulation (altered) of D2 associated with cocaine
2) Confidence 0.22 Published 1998 Journal Brain Res. Mol. Brain Res. Section Abstract Doc Link 9602109 Disease Relevance 0 Pain Relevance 0.74
In bilaterally ovariectomized rats, blocking the cholinergic system on D1 or D2 resulted in higher testosterone serum levels than those observed in castrated rats (both ovaries removed).
Negative_regulation (blocking) of D2 in ovaries
3) Confidence 0.15 Published 2006 Journal Reprod Biol Endocrinol Section Body Doc Link PMC1448196 Disease Relevance 0 Pain Relevance 0
These data suggest that the cyclic AMP production induced in rat neostriatum by simultaneous D-1 and D-2 dopamine receptor activation may be inhibited through mu-opioid receptors, whereas on blockade of D-2 dopamine receptors both mu- and delta-opioid receptors may be linked to adenylate cyclase in an inhibitory fashion.
Negative_regulation (blockade) of D-2 associated with dopamine receptor, mu opioid receptor and delta opioid receptors
4) Confidence 0.15 Published 1985 Journal Eur. J. Pharmacol. Section Abstract Doc Link 2417870 Disease Relevance 0 Pain Relevance 1.04
Furthermore, [D-Ala2, D-Leu5]enkephalin inhibition of glutamate-evoked acetylcholine release was prevented by D2 antagonists in a concentration-dependent manner.
Negative_regulation (inhibition) of D-Ala2 associated with glutamate, antagonist and enkephalin
5) Confidence 0.13 Published 1991 Journal Neuroscience Section Abstract Doc Link 1683474 Disease Relevance 0 Pain Relevance 1.91
Indeed, haloperidol does not induce catalepsy in D2 knockout mice [32], demonstrating that EPS are specifically due to the blockade of D2 receptors.
Negative_regulation (blockade) of D2 associated with targeted disruption and catalepsy
6) Confidence 0.11 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2704377 Disease Relevance 0.47 Pain Relevance 0.09
Although ethanol withdrawal is associated with enhanced sensitivity to dopamine in animals and humans, only minor changes in the striatal density of dopamine D2 receptors have been found in humans, and animals show a small reduction in striatal D2 receptors.
Negative_regulation (reduction) of D2 associated with dopamine and withdrawal
7) Confidence 0.09 Published 2004 Journal Synapse Section Abstract Doc Link 15034913 Disease Relevance 0.41 Pain Relevance 0.68
The dopaminergic suppression of synaptic transmission is therefore mediated by a D2 receptor-dependent reduction in transmitter release, and a D1 receptor-dependent increase in a K+ conductance.
Negative_regulation (reduction) of D2
8) Confidence 0.08 Published 2008 Journal Neural Plasticity Section Abstract Doc Link PMC2519792 Disease Relevance 0 Pain Relevance 0.23
However, blockade of D2 receptors with
Negative_regulation (blockade) of D2
9) Confidence 0.08 Published 2008 Journal Neural Plasticity Section Body Doc Link PMC2519792 Disease Relevance 0 Pain Relevance 0.54
is still possible that dopamine may reduce spiking via a D2 receptor-mediated reduction in INaP [71].


Negative_regulation (reduction) of D2 associated with dopamine
10) Confidence 0.08 Published 2008 Journal Neural Plasticity Section Body Doc Link PMC2519792 Disease Relevance 0 Pain Relevance 0.24
D2 receptors have also
Negative_regulation (receptors) of D2
11) Confidence 0.08 Published 2008 Journal Neural Plasticity Section Body Doc Link PMC2519792 Disease Relevance 0 Pain Relevance 0.42
Blockade of D2-like receptors greatly reduced the suppression of EPSPs.
Negative_regulation (Blockade) of D2
12) Confidence 0.08 Published 2008 Journal Neural Plasticity Section Abstract Doc Link PMC2519792 Disease Relevance 0 Pain Relevance 0.26
Whereas the effects of beta-endorphin, DAGO and [D-Ala2,D-Leu5]enkephalin could be reduced by the mu-preferential antagonist naloxone, the effects of ethylketocyclazocine and U-50488 were not changed.
Negative_regulation (reduced) of D-Ala2 associated with antagonist, narcan and enkephalin
13) Confidence 0.07 Published 1987 Journal Naunyn Schmiedebergs Arch. Pharmacol. Section Abstract Doc Link 3037389 Disease Relevance 0.12 Pain Relevance 1.23
prevented by blockade of D1, but not D2, receptors,
Negative_regulation (blockade) of D2
14) Confidence 0.07 Published 2008 Journal Neural Plasticity Section Body Doc Link PMC2519792 Disease Relevance 0 Pain Relevance 0.33
It can therefore be inferred that the loss of D2 postsynaptic and presynaptic inhibition in the striatum and GPe would result in hyperactivity of the striatopallidal neurons, resulting in inhibition (presumably GABA-mediated) of the GPe neurons, which would then result in increased arousal.
Negative_regulation (inhibition) of D2 in neurons associated with gaba and attention deficit hyperactivity disorder
15) Confidence 0.07 Published 2010 Journal Frontiers in Neuroanatomy Section Body Doc Link PMC2996256 Disease Relevance 0.17 Pain Relevance 0.38
But how can dopamine-related functions be increased in ethanol withdrawal in the face of an unchanged or reduced density of dopamine D2 receptors?
Neg (unchanged) Negative_regulation (reduced) of D2 in face associated with dopamine and withdrawal
16) Confidence 0.06 Published 2004 Journal Synapse Section Abstract Doc Link 15034913 Disease Relevance 0.39 Pain Relevance 0.71
Since our model predicts that the loss of D2 receptors in the BG may result in an increase in wakefulness, the reduced wakefulness in D2 knockout mice may be due to the absence of functional D2 receptors in the extra-BG sites, such as the cerebral cortex, BF, LH, and other wake-promoting cell groups in the brainstem and caudal hypothalamus (Figure 2B).
Negative_regulation (absence) of D2 in brainstem associated with targeted disruption, medulla and cerebral cortex
17) Confidence 0.06 Published 2010 Journal Frontiers in Neuroanatomy Section Body Doc Link PMC2996256 Disease Relevance 0.34 Pain Relevance 0.26
D1 and D2 dopaminergic receptors are abundantly expressed in the cerebral cortex while D1, D2, D3, and D5 receptors are expressed in the striatum and D2, D3, and D5 receptors are expressed in the GPe.
Negative_regulation (receptors) of D2 in striatum associated with cerebral cortex
18) Confidence 0.06 Published 2010 Journal Frontiers in Neuroanatomy Section Body Doc Link PMC2996256 Disease Relevance 0 Pain Relevance 0.36
Since our model predicts that the loss of D2 receptors in the BG may result in an increase in wakefulness, the reduced wakefulness in D2 knockout mice may be due to the absence of functional D2 receptors in the extra-BG sites, such as the cerebral cortex, BF, LH, and other wake-promoting cell groups in the brainstem and caudal hypothalamus (Figure 2B).
Negative_regulation (loss) of D2 in brainstem associated with targeted disruption, medulla and cerebral cortex
19) Confidence 0.06 Published 2010 Journal Frontiers in Neuroanatomy Section Body Doc Link PMC2996256 Disease Relevance 0.35 Pain Relevance 0.28
Otherwise it is difficult to integrate anatomical studies indicating that MSNs project sequentially rather than in parallel to their major target areas [32,33], with physiological studies showing D2 inhibition of MSN projections to pallidal neurons [28] and D1 facilitation on projections to the ventral midbrain [25], and data showing extensive co-expression of D1 and D2-like receptors in MSNs [29,31,62].
Spec (like) Negative_regulation (inhibition) of D2 in midbrain associated with midbrain
20) Confidence 0.05 Published 2006 Journal BMC Neurosci Section Body Doc Link PMC1538613 Disease Relevance 0.14 Pain Relevance 0.17

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