low dose agonist cause receptor upregulation?

[aspiringchemist]

Im somewhat new to learning about receptor up/down regulation.
Would a daily low dose of amphetamine result in dopamine receptor upregulation? And if so, can someone explain the reason this would occur?

I know that heavy use results in down regulation and understand this moderately.

any information is much appreciated!

 

[Cotcha Yankinov]

I don't believe a low dose of an agonist would cause receptor upregulation, its possible that some preferential action on pre-synaptic autoreceptors would result in a decrease in dopamine release and then a bit of an upregulation of post-synaptic receptors. This is akin to low doses of a dopamine receptor antagonist leading to increases in dopamine release, by virtue of autoreceptor blockade.

 

[Limpet_Chicken]

Selective D2Sh isoform antagonists apparently do seem to possess stimulant properties (D2Sh being the autoreceptor)

https://en.wikipedia.org/wiki/UH-232 (also a weak partial D3 agonist, but reportedly posesses stimulant effects and blocks behavioral actions of cocaine)

And theres oddball neuroleptics like the benzamides, sulpiride and amisulpiride in particular come to mind, whilst at high doses they are classic D2 blocking APs, lower doses reportedly cause an activating effect. Although in this case the waters are muddied somewhat by the GHBr agonist effects, although not sure what sort of dose ranges cause the GHB receptor agonism, and it can't be all THAT powerful as a GHB receptor agonist or we'd be seeing neurotoxicity and seizures everywhere.