# Neurotransmitters and up/downregulation of vesicles/receptors **URL:** \ **Category:** Factual Questions\ **Created:** [February 26, 2016, 5:05pm UTC](https://boards.straightdope.com/t/neurotransmitters-and-up-downregulation-of-vesicles-receptors/747218 "2016-02-26T17:05:12Z")\ **Posts on this page:** 1\ **Page:** 1
**Author:** ![MichaelEmouse](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/michaelemouse/32/101_2.png) [@MichaelEmouse](https://boards.straightdope.com/u/MichaelEmouse)\ **Post date:** [February 26, 2016, 5:05pm UTC](https://boards.straightdope.com/t/neurotransmitters-and-up-downregulation-of-vesicles-receptors/747218/1 "2016-02-26T17:05:12Z")
I’m aware that the current base of knowledge on neurochemistry is hardly comprehensive so I’m looking for what the evidence and educated guesses suggest. 1. I was under the impression that the antagonists of a given post-synaptic receptor will result in its downregulation and agonists in its upregulation. The consensus seems to be that: “Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked by chronic administration of selective serotonin reuptake inhibitors (SSRIs) and classical antipsychotics. Deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These findings suggest that post-synaptic 5-HT2A overdensity is involved in the pathogenesis of depression.” [5-HT2A receptor - Wikipedia](https://en.wikipedia.org/wiki/5-HT2A_receptor) “An overactivity of 5-HT2C receptors may contribute to depressive and anxiety symptoms in a certain population of patients. Activation of 5-HT2C by serotonin is responsible for many of the negative side effects of SSRI and SNRI medications, such as sertraline, paroxetine, venlafaxine, and others. Some of the initial anxiety caused by SSRIs is due to excessive signalling at 5-HT2C. Over a period of 1–2 weeks, the receptor begins to downregulate, along with the downregulation of 5-HT2A, 5-HT1A, and other serotonin receptors. This downregulation parallels the onset of the clinical benefits of SSRIs.” > **[5-HT2C receptor](https://en.wikipedia.org/wiki/5-HT2C_receptor)** > > 3358 15560 n/a ENSMUSG00000041380 Antidepressants and antipsychotics are nearly always antagonists of 5-HT2A and 5-HT2C, correct? This would suggest that 5-HT1A, 5-HT2A and 5-HT2C antagonists cause downregulation of those receptors which would then cause in anxiolytic and antidepressant effects. The following may be accurate or a mistake from an overenthusiastic contributor: “There is cross tolerance among psilocin, mescaline, LSD,[8] and other 5-HT2A, 5-HT2C, and 5-HT1A agonists due to down-regulation of these receptors.” > **[Psilocin](https://en.wikipedia.org/wiki/Psilocin)** > > Psilocin (also known as 4-HO-DMT, 4-hydroxy DMT, psilocine, psilocyn, or psilotsin) is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the 5-HT2A receptors, psilocin modulates the production and reuptake of serotonin. The mind-altering effects of psilocin are highly variabl Psilocin... So, do those substances result in downregulation of those receptors? Is the cross tolerance due to a different effect? Do those substances result in upregulation of those receptors? If so, what might explain their therapeutic potential\*? 1. I’ve gotten the impression that psychotropic substances whose effective dose is close to the neurotoxic dose are often releasing agents. Is this accurate? If so, why? Can releasing agents result in upregulation of synaptic vesicles? \*[Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles - PMC](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104707/)