Monoamine mediation of the morphine‐induced activation of mice

Article date: September 1972

By: BERNARD J. CARROLL, PETER T. SHARP in Volume 46, Issue 1, pages 124-139

. The dose‐response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established.

. The activation response can be modified by drugs which affect either catecholamines or indoleamines.

. The monoamine precursors l‐DOPA and 5‐hydroxytryptophan potentiate the response.

. The monoamine synthesis inhibitors α‐methyl‐p‐tyrosine and p‐chlorophenylalanine reduce the response.

. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation.

. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine.

. Blockade of α‐adrenoceptors with phentolamine or phenoxybenzamine reduced the response.

. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response.

. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard.

. The tricyclic antidepressant drug imipramine potentiated the response.

. The morphine antagonist nalorphine completely prevented the response.

. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response.

. 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.

. The dose‐response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established.

. The activation response can be modified by drugs which affect either catecholamines or indoleamines.

. The monoamine precursors l‐DOPA and 5‐hydroxytryptophan potentiate the response.

. The monoamine synthesis inhibitors α‐methyl‐p‐tyrosine and p‐chlorophenylalanine reduce the response.

. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation.

. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine.

. Blockade of α‐adrenoceptors with phentolamine or phenoxybenzamine reduced the response.

. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response.

. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard.

. The tricyclic antidepressant drug imipramine potentiated the response.

. The morphine antagonist nalorphine completely prevented the response.

. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response.

. 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.

DOI: 10.1111/j.1476-5381.1972.tb06855.x

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