Serotonin Autoreceptors

As for NE neurons, 5HT neurons are endowed with cell body and terminal autoreceptors that exert a negative feedback influence on neuronal firing and release, respectively. The somatodendritic ones that inhibit firing rate are of the 5HT1A subtype, and the ones located on terminals are mainly of the 5HT1B subtype. The former subtypes of auto-receptors play a crucial role in the antidepressant effect of 5HT reuptake blockers and monoamine oxidase inhibitors because they desensitize after 2 to 3 weeks of treatment. This permits a recovery of the firing rate of 5HT neurons to normal in the presence of inhibited reuptake or monoamine oxidase inhibition, then producing a net increase in neurotransmission. The time course for this recovery in firing activity is consistent with the onset of the therapeutic action of such drugs in major depression. This observation has recently been put to clinical use by accelerating the anti-depressant response of such drugs with the 5HT1A auto-receptor antagonist pindolol. Eight of the first ten placebo-controlled studies documented a 7- to 14-day acceleration with this strategy.

There are 5HT1D autoreceptors at the level of the cell body of 5HT neurons that exert an inhibitory role on 5HT release in the midbrain and thus, indirectly, on terminal 5HT release through a 5HT1A autoreceptor interaction. Finally, 5HT3 receptor activation, under certain experimental conditions, enhances 5HT release and was prematurely attributed to an autoreceptor function. Subsequent experiments have, however, revealed that these receptors are not located on 5HT neurons and, until proven otherwise, should not be considered autoreceptors.

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Anxiety and Depression 101

Anxiety and Depression 101

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