Endogenous Enkephalins, Depression and Antidepressants

Abstract

A series of clinical and experimental observations support the notion that cerebral opioid peptides may play a role in mood regulation and could be involved in the pathophysiology of affective disorders and the action of antimanic and anti-depressant treatments. The oldest evidence for this hypothesis is that for many years, before the advent of tricyclic antidepressants, the ‘opium cure’ was used with some beneficial effect in the treatment of depressed patients in spite of obvious side-effects. Indeed, the three families of opioid peptides and their receptors are particularly abundant in several limbic structures believed to be involved in mood regulation (Cuello, 1983). Stimulation of these receptors by opiates has been known for centuries to have hedonic actions in humans, eliciting a dream-like euphoria, for which presumably they have been self-administered. It has even been hypothetised that opiate-dependent individuals become addicted because opiates relieve their depressive symptoms (McLellan et al., 1982). A slight antidepressant activity of morphine has been reported (Extein et al., 1981). Also, buprenorphine, a partial agonist at opiate receptors, was recently shown to ameliorate symptoms in depressed patients (Emrich et al., 1982). Similar observations were made following the intravenous administration of β-endorphin (Kline et al., 1977; Angst et al., 1977; Gerner et al., 1980) but could not be replicated in another study (Pickar et al., 1981).