Participation of [Met⁵]-enkephalin in the action of antipsychotic drugs

Abstract

Several lines of indirect investigation indicate that the two polypeptides, [Leu⁵] and [Met⁵]-enkephalin which are stored in brain neurons and function as endogenous ligands for opiate receptors may be operative in a number of brain functions including regulation of extrapyramidal motility, reward seeking behavior and responsiveness to aversive stimuli. This notion is consistent with the high content of [Met⁵]-enkephalin in striatum, nucleus accumbens, amygdala and nucleus interpeduncularis (Hong et al., 1977b). In rats, the intraventricular injection of β-endorphin, like that of morphine, decreases spontaneous motor activity, elicits muscular rigidity (Bloom et al., 1977) and reduces the acetylcholine metabolism in hippocampus via a regulation of the trans-synaptic activation taking place in septum (Moroni et al., 1977a, b). Belluzzi and Stein (1977) reported that the pattern of [Met⁵] and [Leu⁵]-enkephalin self-administration in rats is consistent with the hypothesis that [Leu⁵] and [Met⁵]-enkephalin mediate the drive-reducing reward function. Thus, they propose a model in which drive-inducing and drive-reducing reward function are mediated by norepinephrine and [Met⁵]-enkephalin, respectively. Furthermore, recent reports concerning clinical experiments with naloxone (Gunne et al., 1977; Davis et al., 1977; Janowsky et al., 1977) and β-endorphin (Kline et al., 1977) on mental patients encourage the working hypothesis that an abnormality in the function of endogenous opiate peptides may be operative in psychosis.