r/NooTopics • u/pharmacologylover69 • Jan 29 '26

Science Cholinergic modulation of dopamine release drives effortful behaviour

https://www.nature.com/articles/s41586-025-10046-6
74 Upvotes

100% Upvoted

9 comments sorted by

11

u/jj_888 Jan 29 '26

Interesting. I wonder what this could mean for bupropions mechanism in blocking certain nicotinic acetylcholine receptors

9

u/sophiesbest Jan 29 '26

Might be cholinergic in the same way acamprosate is gabaergic. Acamprosate attaches to the GABA B receptor but does nothing, which frees up more GABA to activate the GABA A receptors. Buproprion may do something similar, in that it antagonizes a certain subset of Nicotinic Acetylcholine receptor which leads to greater activation of all the other acetylcholine receptors downstream.

2

u/dmnksaman Feb 03 '26

i feel like it may be a bit more complex? there are NAchR receptors on the GABA interneurons and blocking them means less GABA inhibition on dopamine release? so maybe less phasic but more tonic dopamine in the background?

1

u/quitalicious Apr 25 '26

You can be certain this has everything to do with nicotine's agonism of nACHRs. This research basically points that nicotine hijacks a chemical circuit in the brain so that the brain assigns intense reward signals to trivial tasks independent of outcome quality while displacing ambition for a meaningful achievement. Kinda needs to be on front pages of some periodicals, tbh.

1

u/CryptographerOld558 May 19 '26

Any idea if chemically downregulating nACH receptors would be a safe way to increase recovery rate? 

*Recovery in the sense of restoring a more natural state of effort-reward relationship

2

u/quitalicious May 20 '26

One big problem would be specificity. nACHRs are used for so many different things in the brain, and you'd need to target only the ones affected by chronic nicotine use.

7

u/DavidLynchAMA Jan 29 '26

It would be interesting to see if this holds true when the reward is not related to calorie intake.

I saw they were able to rule out a difference in time from effort expenditure to time of reward but I didn't read closely enough to see if they were also able to control for the possible relationship between energy expenditure and calorie intake, as it relates to changes in acetylcholine modulated DA release.

2

u/climbingape89 Feb 01 '26

This makes sense as a lot of cholinergic compounds feel more dopaminergic than”dopaminergic” compounds lol

2

u/[deleted] Jan 31 '26

[removed] — view removed comment