Receptor upregulation, possible?

[brickhouse50]

Most drugs may cause receptor downregulation (such as MDMA, amphetamines, etc).

Are there any substances which cause receptor upregulation? Would this work in theory? What if you lower your level of neurotransmitters available; would the receptors up-regulate to compensate?

 

[kyanite]

Doesn't caffeine upregulate adenosine receptors. And then when people with high tolerance stop taking it, they become sensitive to adenosine and get low blood pressure and what not. At least thats what wiki says.

 

[Dr.Heckyll]

Some drugs up-regulate receptors:

J Neurochem. 2006 Oct 5;

Up-regulation of dopamine D(2)L mRNA levels in the ventral tegmental area and dorsal striatum of amphetamine-sensitized C57BL/6 mice: role of Ca(v)1.3 L-type Ca(2+) channels.Giordano TP 3rd, Satpute SS, Striessnig J, Kosofsky BE, Rajadhyaksha AM.
Laboratory of Molecular and Developmental Neuroscience and Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

Dopamine D(2) long (D(2)L) and D(2) short (D(2)S) isoforms of the D(2) receptor play an important role in psychostimulant-induced neuronal adaptations. In this study, we used quantitative real-time PCR to specifically amplify these two splice variants to examine their mRNA expression in the dorsal striatum (dStr), nucleus accumbens (NAc) and the ventral tegmental area (VTA) of amphetamine-sensitized C57BL/6 mice. We found a significant increase in D(2)L mRNA in the VTA and dStr of amphetamine-treated mice that positively correlated with the sensitized locomotor response. We also found a significant increase in D(2)S mRNA in the VTA. We further examined the role of the Ca(v)1.3 subtype of L-type Ca(2+) channels in up-regulation of D(2)L and D(2)S mRNA in the VTA. Amphetamine-pretreated Ca(v)1.3 wild-type (Ca(v)1.3(+/+)) mice exhibited sensitized behavior and a significant increase in D(2)L and D(2)S mRNA compared with saline-pretreated mice Amphetamine-pretreated homozygous Ca(v)1.3 knockout (Ca(v)1.3(-/-)) mice did not exhibit sensitized behavior. There was a significant increase in D(2)S mRNA, but not D(2)L mRNA. In conclusion, our results find that amphetamine increases D(2)L mRNA expression in the dStr and the VTA, an adaptation that correlates with expression of sensitized behavior and dependence on Ca(v)1.3 Ca(2+) channels.

PMID: 17026527

 

[brickhouse50]

Would up-regulating receptors such as serotonin and dopamine receptors stand a chance in reversing drug-induced depression/amotivation, and perhaps even in reversing tolerance to amphetamines/MDMA/other drugs, thus giving stronger highs?

 

[Helios.]

Receptor Upregulation.

I have heard of the term 'reverse tolerance' being used to describe this phenomenon; however, I am not aware of many--if any--drugs that fit the bill.

The only example I can think of is smoked cannabis in the drug naive subject sometimes requiring several smoking sessions before a high is achieved, and that phenomenon generally only occurs once per individual and may or may not be a strict example of receptor upregulation / reverse tolerance.

Receptor downregulation leading to tolerance is the rule of thumb in the drugs of abuse/recreation/enlightenment world.

 

[DadeMurphy]

Upregulation + sensitization can also occur as a response to some sort of injury that leads to chronically low levels of neurotransmitter. The best example I can think of is in the somatic nervous system, when a nerve is severed and ceases to function, the tissues it innervated may become sensitized, meaning if stimulated artificially there is a much stronger response than normally. This aids in the repair of that nerve's funtion.