Im not sure if this is in the correct forum, i am new here. Basically my first question is about the desensitization of receptors, namely dopamine. Now, when overstimulated by substances such as stimulants, desensitization occurs. Is this effect permanent? My thought is no. So if not permanent, how do these receptor sites get back to "normal"? How does the "healing" process differ when recovering from different strenght stimulants (caffien, adderall (d-amphetamine salts), cocain, etc.) and what other details would affect the "healing" process? Length of use? Dosages used?

To me, logically the answers would be that the more powerfull the stimulant, the higher the dose, and the longer it was used for would all contribute to a longer recovery period.

Thank you.

Interesting question. Off the top of my head, I would expect that kinases and phosphatases play a role.

even looking up the definitions did not help me understand the response. maybe i should clarify that i am very inexperienced in neurobiology and just begining my interest in it now in my early years of college.

Could you provide a simpler response either confirming or denying my assumption that if a receptor site does desensitize, it goes back to normal once the action that caused the overstimulation is stopped.

http://www.ncbi.nlm.nih.gov/entrez/query.f...xt%20Word%5D%29


phosphorylation (attaching phosphate residues to proteins) is a common means to regulate the activity of proteins. My expectation is that dopamine receptors may become desensitized when they become phosphorylated. The link above supports that, but searching more through Pubmed would yield more info.

Kinases are proteins that phosphorylate other proteins, whereas phosphatases dephosphorylate other proteins. See http://en.wikipedia.org/wiki/Kinase and http://en.wikipedia.org/wiki/Phosphatase

Again, i do apologize for the simplicity of the questions. I am not reffering to how the receptors may beome desensitized, but as to whether or not they can go back to normal, or to the sensetivity they were at before they were overstimulated. OR is there permanent damage in desensitizing receptors.

thank you.

to my knowledge, desensitization is a temporary phenomena. However, there are physiological responses that may seem like desensitization but are really something else, and are longer lasting. I guess the question is, is desensitization attributed solely to phosphorylation/dephosphorylation, or is it meant as a catch-all term for a decrease in physiological or psychological sensitivity to something? For example, some drugs will produce a response only the first few times when tried, and then fail to elicit a similar response even if not taken for months or years. Is this due to desensitization of receptors (through phosphorylation or dephosphorylation), to up- or down-regulation of receptors, or some more permanent alteration in neurochemistry or even neural circuitry? I don't know. In terms of recovering from drugs, this can take months to get back to normal. Regarding the underlying reason, it very likely is not just desensitization, but something more prolonged like altered receptor clustering and the expression of certain genes that mediate a prolonged cascade of responses to counter the effect produced by the drug.

Usually it is temporary, although it really depends on where you are talking about as well. If you experience very little physical pain in your life, then you will be more sensitive to pain. If you go through alot of physical pain, your receptors will be less sensitive to it.

Its really just your body adapting to your environment. You can pretty much change neuron sensitivity either way, making it more or less sensitive. Its a matter of adaptation.

thanks for the replys, i have more questions regarding effects of adderall (D salt amphetamine combination) specifically which i will address in a new thread.

pokerpro,
At a single receptor level desensitization is a temporary phenomenon. It has nothing to do with the dose of the "stimulant" but may have to do with its "strength" and duration of stimulation. It is important to understand that desensitization refers to the inactivity of the receptor protein despite the continued presence of the agonist ("stimulant"). For example, many receptors open and allow current through once an agonist binds to them; such receptors will often close after some time even though the agonist is still bound. That is desensitization. Receptor proteins may fluctuate between the desensitized (non-conductive) state and the open state or the agonist may unbind leading to an inactive closed state of the receptor. Once the agonist leaves the receptor, higher dose affects desensitization only in the sense that there are more new molecules to bind the vacant agonist binding sites on the receptor and create another opportunity for that receptor to desensitize. However, I think you are using "desensitization" to describe the lack of the response of a receptor to a "stimulant" when it has previously responded to it. This could be due to a number of factors including downregulation of the receptor expression (receptors are not there anymore to respond to an agonist) and reduced sensitivity of the receptor to an agonist (due, for example, to phosphorylation events). I hope this helps.

Desensitization as far as amphetamines go actually refers to a positive effect of the brain reacting in a more favorable way to the amp over time. A sort of bizzare anti-tolerance that for some reason occurs only with amphetamine (cocaine is claimed to hold this property also but i doubt it). The effect has something to do with how amp forces DAT to dump dopamine into the neuronal cleft, the only drug i know of that does anything even close to similar is MDMA which of course was engineered with that exact purpose in mind only working on serotonin transporters.