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ADHD: misbalance between activation of D1 and D2

adhd dopamine add

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#1 ta5

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Posted 24 October 2018 - 02:50 AM


Any comments on this? Anything we could try if this theory is correct? 

 

Front Integr Neurosci. 2018 Oct 5;12:45.

Natsheh JY, Shiflett MW5.
Aside from its clinical symptoms of inattention, impulsivity and hyperactivity, patients with Attention/Deficit-Hyperactivity Disorder (ADHD) display reward and motivational impairments. These impairments may reflect a deficit in action control, that is, an inability to flexibly adapt behavior to changing consequences. We previously showed that spontaneously hypertensive rats (SHR), an inbred rodent model of ADHD, show impairments in goal-directed action control, and instead are predominated by habits. In this study, we examined the effects of specific dopamine receptor sub-type (D1 and D2) agonists and antagonists on goal-directed behavior in SHR and the normotensive inbred control strain Wistar-Kyoto (WKY) rats. Rats acquired an instrumental response for different-flavored food rewards. A selective-satiety outcome devaluation procedure followed by a choice test in extinction revealed outcome-insensitive habitual behavior in SHR rats. Outcome-sensitive goal-directed behavior was restored in SHR rats following injection prior to the choice test of the dopamine D2 receptor agonist Quinpirole or dopamine D1 receptor antagonist SCH23390, whereas WKY rats showed habitual responding following exposure to these drugs. This novel finding indicates that the core behavioral deficit in ADHD might not be a consequence of dopamine hypofunction, but rather is due to a misbalance between activation of dopamine D1 and D2 receptor pathways that govern action control.
PMID: 30344481

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#2 gamesguru

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Posted 25 October 2018 - 03:03 AM

The spontaneously hypertensive rat is not exclusively representative of the "ADHD" phenotype, rather it is a melting pot of anxio-depressive and psychotomimetic effects, one which is hardly reminiscent of a well-controlled anything.  The authors jump from one assumption to the next without drawing any firm connections between.  ADHD is taken as an inflexible response to novelty, this is supposedly modeled by the SHR, which in turn serves as an adequate human model?  Much convincing remains.

 

Anyways, this loosely confirms what we know already.  D1 antagonists modulate motor excitement and hyperactivity, while D2 agonists promote the flowing focus about which school parents are so incredulous.  Without testing more ligands, we can't rush to any broad conclusions.  The D2 agonist in red ginseng may be slightly attenuate Parkinson's disease while making inattention worse.  Meanwhile a lab compound with similar (or perhaps even opposite) bindings may induce a favorable response on both.  And how are we to get to the bottom of that and offer general recommendations?  And how are we to make sense of that?

 

I would take this on an individual basis, and this study may have more relevance for the motivational component than the inattentive one.  Regardless it encourages you to go dosing up on random lab synths and obscure botanicals in the hopes of curing yourself, which I of course must discourage so long as it is purely random.


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#3 graatch

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Posted 06 January 2019 - 03:59 AM

Working memory training appears, according to several separate investigations, to be able to sensitize D1 dopamine receptors in various regions.

 

https://www.ncbi.nlm...pubmed/19197069

 

 

 

Science. 2009 Feb 6;323(5915):800-2. doi: 10.1126/science.1166102.
Changes in cortical dopamine D1 receptor binding associated with cognitive training.
Abstract

Working memory is a key function for human cognition, dependent on adequate dopamine neurotransmission. Here we show that the training of working memory, which improves working memory capacity, is associated with changes in the density of cortical dopamine D1 receptors. Fourteen hours of training over 5 weeks was associated with changes in both prefrontal and parietal D1 binding potential. This plasticity of the dopamine D1 receptor system demonstrates a reciprocal interplay between mental activity and brain biochemistry in vivo.

 

 

 

For some reason they split it into a primary paper and a supplement which contains most of the details. I've attached them.

 

Training:
 
Prior to training the participants were briefed by a psychologist, either by telephone or in person. Each participant installed the training software on their home computer. Each training session included 100-150 trials, (30 to 45 minutes in total). Participants completed on average 23.9 (s.d. 1.8) training sessions during a 5 week period, with no more than one training session per day. 
 
There were 10 different training tasks. An adaptive algorithm was used to adjust the WM load in line with performance, ensuring that participants trained at a level that matched their performance. The tasks were as follows: i) to remember a sequence of dots appearing on a stationary grid, and repeat the sequence in the same order; ii) to remember a sequence of positions appearing on the sides of a cube, and repeat the sequence in the same order; iii) to remember a sequence of dots appearing on a circular rotating grid, and repeat the sequence in the same order; iv) to remember a sequence of dots appearing on a rotating rectangular grid, and repeat the sequence in the same order; v) to remember a sequence of cubes which moved around the screen, and repeat the sequence in the same order; vi) to remember a sequence of dots which appeared at different positions on a circular grid, and a sequence of letters which they heard at the same time as the dots were displayed, and recall both in the same order; vii) to remember a sequence of heard letters, and repeat the sequence in the same order; viii) to remember a sequence of heard syllables, and repeat the sequence in the same order; ix) to remember a sequence of heard numbers, and repeat the sequence in the same order; x) to remember a sequence of visually presented numbers, and repeat the sequence in the reverse order. 
 
Following each training session the results were automatically sent to the psychologist, who monitored progress, and gave feedback during training.

 

 

 

Here's another paper on the matter, they used an n-back task: https://www.ncbi.nlm...les/PMC5540932/

 

And another: https://www.ncbi.nlm...les/PMC4575686/

 

Attached Files


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#4 kurdishfella

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Posted 20 October 2022 - 08:00 PM

 

 

banned so fast for asking elsewhere but inbred rodent model of ADHD, caus..

Are there any benefits to inbreeding? I know in the past they did it to make sure they would incarnate into the same families to retain power. they believed in spirit.


Edited by kurdishfella, 20 October 2022 - 08:00 PM.






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