Regulation of dorsal raphe nucleus function by serotonin autoreceptors: A behavioral perspective

Neurotransmission by serotonin (5-HT) is tightly regulated by several autoreceptors that fine-tune serotonergic neurotransmission through negative feedback inhibition at the cell bodies (predominantly 5-HT1A) or at the axon terminals (predominantly 5-HT1B); however, more subtle roles for 5-HT1D and 5-HT2B autoreceptors have also been detected. This review provides an overview of 5-HT autoreceptors, focusing on their contribution in animal behavioral models of stress and emotion. Experiments targeting 5-HT autoreceptors in awake, behaving animals have generally shown that increasing autoreceptor feedback is anxiolytic and rewarding, while enhanced 5-HT function is aversive and anxiogenic; however, the role of serotonergic activity in behavioral models of helplessness is more complex. The prevailing model suggests that 5-HT autoreceptors become desensitized in response to stress exposure and antidepressant administration, two seemingly opposite manipulations. Thus there are still unresolved questions regarding the role of these receptors—and serotonin in general—in normal and pathological states.

► In this review of serotonin autoreceptors, we primarily cover the role of 5-HT1A and 5-HT1B receptors in regulating behavior. ► Overall, activation of these autoreceptors is rewarding and anxiolytic, but has more complex effects in models of helplessness. ► Both stress and antidepressant treatment appear to desensitize these autoreceptors.