Receptor up/down regulation

[dr_ee_greg]

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Hi,

Has anyone seen any good articles on how long it takes receptors to up and down regulate,
particularity for gaba and dopamine receptors when exposed to different drugs and after the drug is discontinued.

Thanks,
Greg

BTW I am not an MD but have a PhD in electrical engineering and specialize in developing software models for physical systems (differential equation solvers etc).

 

[FlowRate]

I've found it difficult in the past to get kinetics data, whether for quantitative phys or computational biology. I suspect this is because, although I'm an MD and have a computational background, I have no clue what to actually search for to get access to such data.

I had a professor here who was versed in PDE's/Multivariate Calc and was willing to give extra tutoring in quantitative renal physio, but alas I found that overwhelming on top of the rest of med school...

If I needed to do this sort of thing, I'd either consult a research librarian or a local computational biology department. Maybe you could find a friendly grad student or post-doc to help you out.

 

[smalltownpsych]

I’m not sure exactly how we would get at the data. Do we have the technology to measure the receptors that well? Even if we could look at the receptors, there are so many other variables at play, how would we interpret it? The presence or absence of neurotransmitters and how they act at a specific synapse is a relatively small part of the picture when we are looking at trying to correlate with grosser measures of neurological function such as mood states, emotional responses, or behavior.

I am thinking this question is likely in reference to the rewards system and addiction so it is a good question to ask. I tell patients that the best thing to do is continue to associate newer and healthier behaviors to the reward system and that it is a gradual process and it takes about a year for it to start to functioning more normally based on my observations and extrapolating from other data on neurological functioning after discontinuation of substances. Age, substances, duration and severity of use all play a role in that.

 

[tr]

Yes you can use PET imaging to obtain this type of information, and there is plenty of it available in the addiction literature. Try searching something like ''dopamine receptor regulation addiction PET.". The below study is classic, it was done in monkeys as human data are typically messier since it isn't considered ethical to impose addiction on humans in order to study it.
There are some good imaging studies of human dopamine receptor recovery after abstinence, will see if I can dig up later when I'm on be a computer. It does take years for full recovery if I recall correctly.


PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys
Michael A Nader, Drake Morgan, H Donald Gage, Susan H Nader, Tonya L Calhoun, Nancy Buchheimer, Richard Ehrenkaufer, Robert H Mach
Nature neuroscience 9 (8), 1050, 2006

 

[okokok]

Yes you can use PET imaging to obtain this type of information, and there is plenty of it available in the addiction literature. Try searching something like ''dopamine receptor regulation addiction PET.". The below study is classic, it was done in monkeys as human data are typically messier since it isn't considered ethical to impose addiction on humans in order to study it.
There are some good imaging studies of human dopamine receptor recovery after abstinence, will see if I can dig up later when I'm on be a computer. It does take years for full recovery if I recall correctly.


PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys
Michael A Nader, Drake Morgan, H Donald Gage, Susan H Nader, Tonya L Calhoun, Nancy Buchheimer, Richard Ehrenkaufer, Robert H Mach
Nature neuroscience 9 (8), 1050, 2006

Thanks for the paper recommendation - I've also tried to find the answers to the OP's question. I'd be interested in the other papers you'd recommend if you have time to find them.

 

[tr]

Sure, try these:

Volkow et al., 2001, Association of Dopamine Transporter Reduction With Psychomotor Impairment in Methamphetamine Abusers
https://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.158.3.377

Volkow et al. 2001, Loss of Dopamine Transporters in Methamphetamine Abusers Recovers with Protracted Abstinence
Loss of Dopamine Transporters in Methamphetamine Abusers Recovers with Protracted Abstinence


I'm not as familiar with the alcohol/GABA receptor literature but I found this after a quick search:

Lingford-Hughes et al., Reduced levels of GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy
Reduced levels of GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy | The British Journal of Psychiatry | Cambridge Core