Gentle reader,
I am happy to announce our recent open-access publication Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN-NBOH in Mice. In this paper we use 25CN-NBOH (see figure), a newly developed tool of pharmacology, and describe it in terms of its basic behavioural dynamics.
Gaining insights into the mechanism of action of serotonergic hallucinogens is difficult because most of the representatives of this class of drugs have the tendency to bind to various target proteins within the brain. Serotonergic hallucinogens bind to these so-called "receptor" proteins located in the membrane of the brain cells, and thereby affect the cells' communication patterns. Given their structural similarity to brain inherent monoaminergic neurotransmitters (which represent the "dialects" neurons use to communicate), serotonergic hallucinogens show a particular preference for receptors belonging to the monoamine neurotransmitter family (most notably those of serotonin, dopamine, and noradrenaline).
Although all binding to the individual receptors is likely to affect the brain in one or another way, not all of the receptors are thought to be primarily involved in the psychedelic action of serotonergic hallucinogens. Instead, a specific member of the serotonin receptor family, namely the 5-HT2A receptor, seems to play a predominate role. With all the noise created by the other receptors, though, it remains an unabated challenge of science to actually tell apart what is 5-HT2A, and what it is that marks this protein out and makes it so peculiar when it comes to conscious experience and the mechanism of action of serotonergic hallucinogens.
25CN-NBOH is a newly developed drug that bypasses a multitude of non5-HT2 receptors and selectively addresses 5-HT2A receptors. Characterising the behavioural and physiological profile of this drug, and tracing it back to its very origins in the brain might therefore help and write a new chapter in the delineation of serotonin as to one of the key narrators of consciousness.
Best, Tobias
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