The Brain Epinephrine-α1-Adrenoceptor System in Behavioral Activation and Depression

Disabling behavioral inactivity is a prominent symptom of a number of psychiatric disorders, most notably, major depressive illness. The neurobiology of these inactive states is currently believed to involve alterations in central serotonergic, noradrenergic or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain α1-adrenoceptors stimulated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems and plays a critical role in behavioral activation and depression. The present review covers the evidence for this system and includes findings that brain α1-adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This “EPI-α1 system” may therefore represent a new target system for disabling inactivity.