View Full Version : Rescuing cocaine-induced PFC hypoactivity prevents compulsive drug seeking


SB_UK
06-18-13, 05:22 AM
Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking (http://www.nature.com/nature/journal/v496/n7445/full/nature12024.html)

Great stuff again - read in seconds so may have read incorrectly - to read in more detail soon:

Compulsive cocaine seeking (motivation,addiction,reward circuitry activation) <-> PFC hypoactivity (cf ADHD - rescued with dexedrine)

Stress -> stress relief (activation of reward circuitry)

Stress -> stress relief (eg compulsive cocaine seeking (motivation,addiction,reward circuitry activation)) <-> PFC hypoactivity (cf ADHD - rescued with dexedrine)

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Stress underlies PFC hypoactivity (in ADHD) mediated by stress relief (reward system activation by cocaine, blood glucose elevation eg carbs/sugar).

Correction - stress elimination first, second dietary modification.

SB_UK
06-18-13, 05:40 AM
VERY INTERESTING PAPER ON MANY LEVELS !!

Optogenetics mentioned:
only ever heard of it here:
http://www.addforums.com/forums/showthread.php?t=146452

Furthermore, compensating for hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking
Photostimulation decreased earned cocaine infusionsPlaying currently on the earphones:
http://www.youtube.com/watch?v=tySZppRS8hg

Have noticed severe appetite suppression when in the sun - ref. shared mechanism cocaine and blood glucose elevation activation of the primitive/chemical (potentially addictive) reward system.

Sun (optogenetics principle) -> reward system activation via a mechansims (non-chemical) which doesn't apply to the primitive/chemical (potentially addictive) reward system.

Lifting us away from a reward mechanism which results in addiction (see paper) - if cranked particularly under stress.

Connection to idea from previously of stress relief seeking (drugs,alcohol,high GI carbs and animal protein) intake promoted by stress.

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Summary
Conditional on a proper reading of the paper.

Incredible overlap between the ADHD story and the story of drug addiction.
This paper may bring the two paradigms together.
We behave (eg in our need for stimulant medication) - very similarly to the the compulsive drug seeking animal studied in this paper.
But but but - we're not addicts - why're we behaving like it ?
In both paradigms we've PFC hypoactivity - why have we PFC hypoactivity.
Solution - increased sensitivity resulting in increased need for stress relief (at its root through blood glucose elevation - the stimulant (dexedrine) must stimulate through blood glucose elvation).
Chronic exposure to stress is the equivalent of chronically taking drug (eg cocaine) - results (now moving back to the paper) - in a vicious cycle between cocaine seeking and PFC hypoactivity.

So - this paper offers a mechanistic understanding of ADHD from the perspective of cocaine usage - where our 'cocaine' is stress sensitivity in an insensitive world.

The ability to rescue PFC hypoactivity with 'light' is fascinating - and an insight is offered into this idea - I think by the pattern I've noticed of appetite suppression (cf blood glucose elevation/reduction) in sunlight.

Also - note the incredible importance of the melanocortin system in appetite regulation - to:
Exposure to UV-B radiation causes an increased melanogenesis.

The sensitive phenotype of ADDers in focus.
Relative to naive and shock-sensitive neurons, shock-resistant neurons required almost twice as much current to elicit an action potential and exhibited significantly smaller input resistance. Thus, the ability of prelimbic cortex neurons to rapidly generate an action potential was compromised in shock-resistant rats. It's not good to be sensitive in an insensitive world.

SB_UK
06-18-13, 06:06 AM
This is a great paper!

2013 is the year we collapse ALL disease.

SB_UK
06-18-13, 06:11 AM
Figure 1 - Prolonged cocaine self-administration induces compulsive cocaine seeking in a subpopulation of rats.Materialism (which exerts itself along the same basic pathway as cocaine/blood glucose elevation) drives addiction - and it's not a lovely fluffy addiction - there's no such thing as fluffy addiction - addiction is *bad*.

SB_UK
06-18-13, 06:29 AM
http://www.ncbi.nlm.nih.gov/pubmed/23137723
Although crude analyses revealed that inattention, hyperactivity, and impulsivity symptoms significantly predicted deficits in short-term memory ... ...Simply this is a statement:
"inattention, hyperactivity, and impulsivity symptoms" <- ADHD [DISORDER COMPONENT] IS A HEIGHTENED REACTION TO STRESS
->- leads to ->-
"deficits in short term memory"

... ... or - the fairly uncontraversial idea that memory is disrupted by stress.

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From 'genetics of dyslexia' -> visuo-spatial and verbal reasoning are the two aspects tested in an IQ test.

Effects in ADHD eg:
"Therefore, our findings suggest that earlier inattention symptoms are associated with impaired verbal and visuo-spatial short-term memory at a later development stage."-*-

The paper in the OP:hypoactive prelimbic cortex neuronsand:
http://www.ncbi.nlm.nih.gov/pubmed/21044660
However, stress impaired retrieval of extinction assessed 24 h later, and this was accompanied by alterations in neuronal activity in both prelimbic and infralimbic cortex. -*-

Sensitivity to stress -> deranges two components of intelligence (visuo-spatial, verbal) and memory -> particularly noteworthy at the level of the prelimbic cortical neurones -> and then returning to the paper in the OP -> PFC:

PFC hypoactivity (cf ADHD - rescued with dexedrine) <-> Compulsive cocaine seeking (motivation,addiction,reward circuitry activation)
We need a world without stress (without social hierarchy in aspects of the material world eg money,power,materialism).

SB_UK
06-18-13, 06:37 AM
https://en.wikipedia.org/wiki/Impulsivity

Lesions of the anterior cingulate cortex have been shown to increase impulsive responding, and lesions to the prelimbic cortex impair attentional performance.

Anterior cingulate cortex - 'social' reward <- lesion equivalent through life in a vicious, competitive world.
Prelimbic cortex - fear <- lesion equivalent through life in a vicious, competitive world.

SB_UK
06-18-13, 07:08 AM
https://en.wikipedia.org/wiki/Impulsivity

Lesions of the anterior cingulate cortex have been shown to increase impulsive responding, and lesions to the prelimbic cortex impair attentional performance.

Anterior cingulate cortex - 'social' reward <- lesion equivalent through life in a vicious, competitive world.
Prelimbic cortex - fear <- lesion equivalent through life in a vicious, competitive world.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783626/
In contrast to IL, microstimulation of PL increased the expression of conditioned fear
IL -- infralimbic cortex
PL -- prelimbic cortex

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So - the model is of a deep relationship between anterior insular cortex, anterior cingulate cortex, prefrontal cortex
- and infralimbic and prelimbic cortex within the prefrontal cortex

SB_UK
06-18-13, 07:15 AM
'fear' is at the root of all of society's woes.

Transduces itself through the PFC into 'mental' derangement and stress relieving (addictive) pursuits ... ... which kill us (collectively) off ... before our time.

Back round to the Mount Athos epi. study - where none of the diseases of Western living are seen, very long lives are lived without succumbing to disease for more than a little while before dying ... ... and people are :-) happy.

That's all.