Neuroanatomical focus for morphine and enkaphalin-induced hypermotility


OPIATE receptors, through which all opiate alkaloids and peptides produce their pharmacological effects, are distributed heterogeneously in the mammalian brain1–3. The highest receptor densities seem to be associated with a number of limbic midbrain and forebrain structures that have been implicated in regulating motivation and emotionality. Although the limbic midbrain region (periven-tricular-periaqueductal grey matter) is a critical focus for the analgesic4–7 and depressant (A.P. and C.S., in preparation) effects of morphine and enkephalin8, nothing is known about the functional significance of opiate receptors in the forebrain. Significantly, the nucleus accumbens (NA) in the limbic forebrain contains a relatively high concentration of opiate receptors2 (C. B. Pert, personal communication). As this structure has a role in motility9,10, an attempt has been made to ascertain whether it is an important focus for the excitatory effects11,12 of opiates on behaviour. We report here that direct injections of morphine. D-Ala4-enkephalin-amide (an enzyme-resistant enkephalin)7,12 and apomorphine (a dopamine agonist) into the nucleus accumbens increased spontaneous motor activity in rats. The excitatory effects of morphine were antagonised by naloxone (an opiate antagonist) and not by haloperidol (a dopaminergic antagonist). Conversely, apomorphine was antagonised by haloperidol and not by naloxone.

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PERT, A., SIVIT, C. Neuroanatomical focus for morphine and enkaphalin-induced hypermotility. Nature 265, 645–647 (1977).

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