Physiological basis underlying antidepressant-induced activation of TrkB receptors
bioRxiv August 31, 2021 O. Alitalo, S. Kohtala, Marko Rosenholm et al. preprint
Both pharmacological and non-pharmacological treatments for depression activate TrkB receptors—a known antidepressant target—by inducing a physiological response linked to sedation. Rapid-acting antidepressants trigger TrkB signaling by evoking a state characterized by electroencephalographic slow-wave activity, behavioral immobility, reduced cerebral glucose utilization, and lowered body temperature. This signaling was not impaired in animals with reduced activity-dependent BDNF release but was diminished by maintaining animals in a warm ambient temperature. Preventing the hypothermic response attenuated the behavioral effects of the rapid-acting antidepressant nitrous oxide. The findings suggest that changes in energy expenditure and thermoregulation are essential, but not sufficient, for antidepressant responses, challenging pharmacology-centric hypotheses and highlighting the role of bioenergetics and thermoregulation.