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Serotonin (5-HT) was identified as a neurotransmitter in the mid-1960s, when several clusters of neurons projecting throughout the cortex from the raphe nuclei in the brainstem were discovered.
It has been shown that the 5-HT2A receptor is most densely localized on the proximal apical dendrites of the cortical (especially layer V) pyramidal cells.
The 5-HT2A receptor, which now seems to be the only shared and clinically important target of hallucinogens, has been found throughout the cortex, and particularly in cortical pyramidal cells (Willins 1997).
It was debated for many years whether the hallucinogens were agonists or antagonists at the 5-HT receptors.
Also, drugs which mimic increased LC activity (methamphetamine) rarely, if ever, cause true hallucinations.
It is possible, however, that the anxiety that can be produced by hallucinogens is in part mediated by their effect on the LC and the increased sensitivity and response to the sensory hallucinations ( Aghajanian and Marek 1999).
Whether the 5-HT2C receptor mediates any of the hallucinogens' truly psychedelic effects is yet to be seen.