Who said ACTH, prolactin, cortisol and heart rate response are psychological response?Well, I guess they were dettermined from blood samples and not from intraspinall liquid or whatever connected with brains.
I agree with Lily, the physiological tolerance for DMT does not necessarily mean the receptors get internalized. As the psychoactivity remains the same I would say it is proof enough that doesn’t happen. Actually, if for example, the 5-HT1A serotonin autoreceptors are more sensitive for the desensitization we could expect an even stronger effects after continuous exposure. That would really be a funny phenomenon.
Besides if somebees would read at least the abstracts of the papers Rhodium cited they would already find the answer. It does seam that the 5-HT2A R gets desensitized also at short exposures, but trough a different mechanism (which is obviously only short lived). However they do not get internalized. There are other much more temporary desensitization mechanisms known. For example, if I remember correctly, the nicotinic receptors can be temporarily desensitized by phosphorylation on the intracellular side if too much of the agonist sticks around for more than just a moment.
This is from the abstract of the first ref in the first post of this thread!
Mechanisms of Ligand-Induced Desensitization of the 5-HT2A Receptor. JPET 300 (2002) 468-477. (
http://jpet.aspetjournals.org/cgi/content/abstract/300/2/468
)
5-HT-induced desensitization of the 5-HT2A receptor involved receptor internalization through a clathrin- and dynamin-dependent process because it was prevented by concanavalin A, monodansylcadaverine, and by expression of the dominant negative mutants betta-arrestin (319–418) and dynamin K44A. Although short-term (i.e., 10 min) 5-HT and ketanserin exposure resulted in the same degree of desensitization, ketanserin-induced desensitization was not prevented by these agents and did not involve receptor internalization. In contrast, prolonged ketanserin exposure (i.e., 2 h) resulted in 5-HT2A receptor internalization through a clathrinand dynamin-dependent process, as was observed after agonist treatment.