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Effects of Pro‐Leu‐Gly‐NH2 (MIF) on the antinociceptive and thermoregulatory actions of morphine and oxotremorine

Some neurohypophyseal hormones, including MIF (Pro-Leu-Gly-NH,), and analogues modify morphine's pharmacological actions. MIF prevents morphine catalepsy in rats (Chiu & Mishra 1979) and affects the development of tolerance and physical dependence (Van Ree & De Wied 1976). Other central actions of MIF include oxotremorine antagonism (Plotnikoff & Kastin 1975), although this is disputed (Bjorkman et al 1980). Most work with MIF in rats has involved single doses and it was shown that the acute pretreatment times can influence the results (Turnbull & Wheeler 1980). Recently, it was shown that MIF has a very short half life in rat plasma, although it is remarkably persistent in human plasma (Witter et al 1980). Thus, problems in demonstrating MIF's pharmacological actions in rats may arise because of its rapid metabolism. Recently, we demonstrated that MIF antagonizes morphine's antinociceptive action when given chronically to rats (Dickinson & Slater 1980). We now present more data on chronic MIF and morphine's thermoregulatory and antinociceptive actions. The specificity of MIF's anti-morphine action was investigated by examining its effects on oxotremorine-induced hypothermia and analgesia in mice.