Serotonin 1A auto-receptors are not sufficient to modulate anxiety in mice.

The neurotransmitter serotonin plays an important role in modulating diverse behavioral traits. Mice lacking the serotonin 1A receptor (Htr1a) show elevated avoidance of novel open spaces, suggesting that it has a role in modulating anxiety behavior. Htr1a is a Gαi -coupled G-protein-coupled receptor expressed on serotonin neurons (auto-receptor), where it mediates negative feedback of serotonin neuron firing.

Impaired chemosensitivity of mouse dorsal raphe serotonergic neurons overexpressing serotonin 1A (Htr1a) receptors.

Background: Serotonergic system participates in a wide range of physiological processes and behaviors, but its role is generally considered as modulatory and noncrucial, especially concerning life-sustaining functions. We recently created a transgenic mouse line in which a functional deficit in serotonin homeostasis due to excessive serotonin autoinhibition was produced by inducing serotonin 1A receptor (Htr1a) overexpression selectively in serotonergic neurons (Htr1a raphe-overexpressing or Htr1a(RO) mice). Htr1a(RO) mice exhibit episodes of autonomic dysregulation, cardiovascular crises and death, resembling those of sudden infant death syndrome (SIDS) and revealing a life-supporting role of serotonergic system in autonomic control.