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Abstract-The effects of narcotic analgesics on the brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels of rats and mice were investigated in relation to our preceding data on the effect of humoral modulators on morphine induced changes in locomotor activity and body temperature of rodents. The results suggest that morphine accelerates the release of brain 5-HT both in rats and mice, and that neither methadone nor pethidine alters the brain 5-HT and 5-HIAA levels in rats. The morphine-induced increase in brain 5-HT turnover is likely to be involved in the morphine-induced decrease in locomotor activity and hypothermia in rats. The activity-decreasing effects of methadone or pethidine, on the other hand, are mediated by mechanisms different from those which mediate the effects of morphine.In contrast, an increase in brain 5-HT turnover in mice apparently does not play an important role on activity-increasing effects of morphine but rather participates in other pharmaco logical effects of morphine.There have been numerous reports which suggest the participation of 5-hydroxy tryptamine (5-HT, serotonin), a putative neurotransmitter in the brain, in some of the pharmacological effects of narcotic analgesics. There are numerous conflicting reports however, on the relation among narcotics, their pharmacological effects, and serotonin.For example, the acute administration of morphine is reported either to produce an increase in cerebral 5-HT turnover in mice (1) and in rats (2, 3), or not to alter the serotonin turnover in mouse brain (4-6). p-Chlorophenylalanine (p-CPA), a serotonin depletor, is shown either to augment the levorphanol-induced running activity in mice (7), to be ineffective on morphine-stimulated locomotor activity of mice (8) and on levorphanol-induced running activity in mice (9), to reduce the morphine-induced hyperactivity in mice (10), or to reverse the morphine-induced hypoactivity to hyperactivity in rats (6,(11)(12)(13). These discrepancies may not be due to species differences only but also to differences in animal suppliers since it is well known that analgesic doses of morphine produce hyperactivity in mice but hypo activity in rats, the morphine-induced change in cerebral 5-HT turnover is prominently different among mice obtained from different suppliers (14), and morphine-induced changes in body temperature of Wistar rats from the same supplier (hyperthermia) are opposite to those of Wistar rats from another supplier (hypothermia) (15). In an attempt at clarification, we studied the effect of narcotic analgesics on the cerebral 5-HT in rodents as the effect of p-CPA on the morphine-induced changes in locomotor activity and in body temperature has already been reported in these animals (13,(16)(17)(18)(19).

Calcium requirements for electrically-induced release of an endogenous opiate receptor ligand in the myenteric plexus-longitudinal muscle strip of the guinea-pig ileum were studied. The naloxone-reversible depression of the electrically evoked contraction caused by stimulation at 10 Hz in normal Krebs solution was markedly reduced by decreasing the calcium concentration in the solution. The depression was greatly diminished by increasing the magnesium concentration in the solution.These results show that the electrically-induced release of an opiate-like material requires calcium ions.

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