Hypothalamo-neurohypophyseal neuropeptides and experimental drug addiction.

Oxytocin, a hypothalamo-neurohypophyseal neuropeptide was found to attenuate the development of tolerance to the analgesic action of morphine, heroin, beta-endorphin or D-Pro2-Met5-enkephalinamide. The effect of oxytocin on morphine tolerance was prevented by N alpha-acetyl-(2-0-methyltyrosine)-oxytocin or penicillamine1-(2-0-methyltyrosine)-lysine8-vasopressin, which are antagonists of oxytocin receptors. Oxytocin dose-dependently attenuated various signs of precipitated morphine withdrawal (e.g., stereotyped jumpings, hypothermia, body weight loss). The neuropeptide diminished intravenous self-administration of heroin in heroin-tolerant rats. It is concluded that brain oxytocin interferes with adaptive components of experimental drug addiction.