Monoamine mediation of the morphine‐induced activation of mice

Summary1 . The dose‐response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established. 2 . The activation response can be modified by drugs which affect either catecholamines or indoleamines. 3 . The monoamine precursors l ‐DOPA and 5‐hydroxytryptophan potentiate the response. 4 . The monoamine synthesis inhibitors α‐methyl‐ p ‐tyrosine and p ‐chlorophenylalanine reduce the response. 5 . Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation. 6 . Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine. 7 . Blockade of α‐adrenoceptors with phentolamine or phenoxybenzamine reduced the response. 8 . Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response. 9 . The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard. 10 . The tricyclic antidepressant drug imipramine potentiated the response. 11 . The morphine antagonist nalorphine completely prevented the response. 12 . The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response. 13 . We conclude that dopamine, noradrenaline and 5‐hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance.