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Re: Why GABA works undopaminergic

Posted by linkadge on June 21, 2020, at 8:25:41

In reply to Re: Why GABA works, posted by undopaminergic on June 20, 2020, at 5:29:46

This hypothesis has been around for a while. Originally the anticholinergic properties of TCAs were thought to be side effects. More recently (with the confirmation of the antidepressant effect of scopolamine) it is apparent that blocking acetylcholine can itself have antidepressant properties. For example, mice lacking m1 and/or m2 receptors are a 'depression resistant' phenotype. Modulating acetylcholine can produce many of the sleep changes associated with depression (i.e. early entry in to REM sleep and increased REM duration). Increased REM may contribute to (or be the consequence of) increased emotional processing. There are some that theorize that even SSRIs work by modulating acetylcholine levels (in the form of increased cholinesterase expression over time).

https://www.bbrfoundation.org/content/potential-root-cause-depression-discovered-narsad-grantee

In animal models, increasing stress leads to an increased sensitivity of muscarinic receptors. This may be an adaptive mechanism (i.e. increased cholinergic output to try and understand / process the stressor). The 'flinders sensitive line' of mice also appears to be supersensitive to acetylcholine. Acetylcholine agonists (and cholinsterase inhibitors) can result in depression. They may also be anti-manic (by reducing dopamine release). Farmers that routinely apply cholinesterase inhibiting pesticides are at greater risk of depression.

Increasing monoamines, can counteract the effects of high acetylcholine, so it may be more of a complimentary theory. As you mention too, cholinergic agonists can be convulsant / produce muscle tension (and anticholinergics can block this). For me, depression is when my thinking becomes trapped. I tend to overthink, and/or think way too 'big picture'. The future seems hopeless and and cannot find any moments of peace. I bough some belladonna extract (tincture). You have to be VERY careful with this stuff. ONE drop needs to be diluted!! But, basically if I get to a place where I simply become incapacitated, I use this. It seems to dramatically reduce the 'emotional overtone', to where I return to being 'here'.

I sometimes use it with marijuanna (which too can be anticholinergic), but again, you need to be very careful. You can get very try mouth and tachycardia.

Linkadge



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poster:linkadge thread:1110736
URL: http://www.dr-bob.org/babble/20200511/msgs/1110905.html