Autoreceptor

An autoreceptor is a type of receptor located on the presynaptic neuron that is activated by the same neurotransmitter released by that neuron. Autoreceptors provide a negative feedback mechanism that regulates neurotransmitter release and synthesis, helping to stabilize synaptic transmission. Most autoreceptors are G protein–coupled receptors that, when activated, inhibit adenylyl cyclase and reduce cAMP levels, or modulate ion channels to decrease calcium influx and increase potassium efflux. The result is a reduction in neurotransmitter release, and in some cases a downregulation of the synthetic pathway.

Autoreceptors occur at presynaptic terminals (terminal autoreceptors) and in somatodendritic regions, where they can influence neuronal firing and transmitter production. They are typically specific to the transmitter they sense, and common examples include alpha-2 adrenergic autoreceptors in noradrenergic neurons, 5-HT1B/1D autoreceptors in serotonergic neurons, D2 autoreceptors in dopaminergic neurons, and GABA_B autoreceptors on GABAergic neurons. Autoreceptors are contrasted with heteroreceptors, which regulate the release of other neurons’ transmitters.

Pharmacologically, autoreceptors are targets for drugs that aim to alter transmitter availability. Antagonists of autoreceptors can increase release, while agonists can decrease it. Chronic exposure can lead to desensitization or downregulation, influencing tolerance and signaling. Understanding autoreceptors helps explain mechanisms of synaptic control, neuromodulation, and the effects of various neuropsychiatric therapies.