Posted by linkadge on December 10, 2019, at 15:36:19
In reply to Re: What do TRD patients take without an MAIO » linkadge, posted by undopaminergic on December 10, 2019, at 12:12:24
>As I understand it, it is through one of the trace >amine receptors that amph. (and PEA) reduce the >spontaneous firing of the presynaptic neuron.
Yes, it may be a dopamine autoreceptor agonist (or functionally interact via TAAR1). Again, amphetamine can have this property too (within a certain dose range, I believe).
>Do TAARs interact with the autoreceptor system, >or do these receptors produce their effect >independently of each other?
I'm not sure. TAAR1 agonist have antidepressant and antipsychotic properties. So, in some ways, amphetamine may counteract some of its psychotomimetic effects.
https://www.ncbi.nlm.nih.gov/pubmed/29636691
"In general, TAAR1 agonists specifically inhibited the rewarding and reinforcing effects of drugs of abuse and drug-abuse related behaviors. Details of the mechanism of TAAR1 remain elusive; however, it is thought to be regulated by its interactions with D2 receptors."
https://www.ncbi.nlm.nih.gov/pubmed/29066851
"We show, first, that the full TAAR1 agonist, RO5256390, dose-dependently blocked cocaine-induced inhibition of DA clearance in slices of the nucleus accumbens."
"Second, subthreshold inhibition of PKA or PKC phosphorylation did not prevent TAAR1 suppression of cocaine effects whereas subeffective doses of the DA D2 receptor antagonist, L-741,626, rescued cocaine's ability to produce changes in DA uptake in the presence of full TAAR1 activation, thus indicating that TAAR1 modulation of cocaine effects requires simultaneous DA D2 receptor activation."
It seems that taar1 agonist somehow interact with (likely?) presynaptic d2 receptors to inhibit dopamine release (?). It suggested that there is an interaction between TAAR1 and gsk-3. Gsk-3 inhibitors (like lithium) have mood stabilizing and (in some cases) antipsychotic qualities and also seems to regulate dopamine systems.
LSD inhibits dopamine firing via TAAR1 receptors.
https://www.ncbi.nlm.nih.gov/pubmed/27544651
I've often wondered if cannabis interacts with TAAR1 in some way. I know that CB2 receptor agonists also inhibit dopamine firing and can prevent sensitization from drugs like cocaine.
"Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1."
https://www.ncbi.nlm.nih.gov/pubmed/25721394
Hence it seems that TAAR1 receptors also regulate post synaptic d2 receptor sensitivity (as do GSK3 inhibitors like lithium / valproate).
There are case reports of amphetamine calming mania. This could be via taar1 agonism. Perhaps some manics have supersentive TAAR1 receptors, leading to an increased sensitivity to this target of amphetamine.
"Low phenethylamine levels and low activation of TAAR1 can cause attention deficit hyperactivity disorder."
https://www.bocsci.com/tag/trace-amine-associated-receptor-1-taar1-430.html
" Methamphetamine is a psychostimulant that is known to exhibit moderate affinity for sigma-1 receptors (σ-1R) expressed in most neuronal cells "
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0250-7
Linkadge
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thread:1106750
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