The effects of
glycine on
morphine-induced hyperactivity, reverse tolerance and postsynaptic
dopamine receptor supersensitivity in mice was examined. A single administration of
morphine (10 mg/kg, s.c.) induced hyperactivity as measured in mice. The
morphine-induced hyperactivity was inhibited by pretreatment with
glycine (100, 200 and 400 mg/kg, i.p.). In addition, it was found repeated administration of
morphine (10 mg/kg, s.c.) to mice daily for 6 days caused an increase in motor activity which could be induced by a subsequent
morphine dose, an effect known as reverse tolerance or sensitization.
Glycine (100, 200 and 400 mg/kg, i.p.) also inhibited
morphine-induced reverse tolerance. Mice that had received 7 daily repeated administrations of
morphine also developed postsynaptic
dopamine receptor supersensitivity, as shown by enhanced ambulatory activity after administration of
apomorphine (2 mg/kg, s.c.).
Glycine inhibited the development of postsynaptic
dopamine receptor supersensitivity induced by repeated administration of
morphine. It is suggested that the inhibitory effects of
glycine might be mediated by dopaminergic (DAergic) transmission. Accordingly, the inhibition by
glycine of the
morphine-induced hyperactivity, reverse tolerance and
dopamine receptor supersensitivity suggests that
glycine might be useful for the treatment of
morphine addiction.