Yumi Sugimoto

The behavioural effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in mice

The effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on the behaviour of mice were studied. 8-OH-DPAT given i.v. in doses greater than 1 mg/kg induced the distinct 5-HT syndrome, including head weaving, hindlimb abduction, forepaw treading and tremor. The 8-OH-DPAT-induced behaviour was not affected by the 5-HT depleter, p-chlorophenylalanine. Reserpine, which depletes monoamines, significantly decreased the head weaving elicited by 8-OH-DPAT, although it did not reduce the other components of the behavioural syndrome. The non-specific 5-HT receptor antagonist, metergoline, attenuated the 8-OH-DPAT-induced behaviour, while the 5-HT2 receptor antagonist, ketanserin, was without effect. In addition, the 5-HT1A receptor antagonist, spiperone, inhibited the 5-HT syndrome elicited by 8-OH-DPAT, while the dopamine receptor antagonist, haloperidol, affected only the head weaving. These results suggest that 8-OH-DPAT-induced behaviour in mice is mediated by the postsynaptic 5-HT1A receptor.

Serotonin-induced hypoglycemia and increased serum insulin levels in mice

The effects of serotonin (5-HT) on plasma glucose levels were studied. 5-HT above 20 mg/kg induced apparent hypoglycemia in mice. The hypoglycemic effects of 5-HT were strongly antagonized by methysergide but only partially inhibited by ketanserin. However, ICS 205-930 was without effect. This indicates that the hypoglycemia induced by 5-HT is mediated by both the 5-HT1 and 5-HT2 receptors. 5-HT also produced an increase in serum immunoreactive insulin (IRI) which was completely inhibited by methysergide and partially antagonized by ketanserin. It is suggested that the 5-HT-induced increase in IRI is elicited by the activation of the 5-HT1 and 5-HT2 receptors, which is similar to the results obtained with plasma glucose. These results indicate that the 5-HT receptors may regulate blood glucose levels by modifying the release of insulin.

Simultaneous determination of tryptophan and its metabolites in mouse brain by high-performance liquid chromatography with fluorometric detection

A new method for the determination of tryptophan and its metabolites in a single mouse brain using high-performance liquid chromatography (HPLC) with fluorometric detection is described. Tryptophan, serotonin, 5-hydroxyindoleacetic acid, indoleacetic acid, and tryptophol were clearly separated by a C8 reverse-phase column. Tissue preparation is performed only to centrifuge homogenates of brain prior to the injection to HPLC. The sensitivity is in the range from 10 to 15 pg.

Activation of peripheral serotonin2 receptors induces hypothermia in mice

The effects of peripherally administered serotonin (5-HT) on the rectal temperature were investigated. 5-HT i.p. induced a dose-dependent hypothermia in mice. The hypothermic effects of 5-HT were strongly antagonized by the 5-HT1 and 5-HT2 receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin. However, the 5-HT1 receptor antagonist pindolol and the 5-HT3 receptor antagonist ICS 205-930 were without effect. In addition, the peripheral 5-HT2 receptor antagonist xylamidine strongly reduced 5-HT-induced hypothermia. These results indicate that the activation of the peripheral 5-HT2 receptors induces hypothermia, although the central 5-HT2 receptors have been suggested to relate to hyperthermia.

The behavioural effects of intravenously administered tryptamine in mice

The behavioural effects of intravenously administered tryptamine were examined in mice. Tryptamine in a dose greater than 15 mg/kg induced distinct head-weaving and hindlimb abduction. These behavioural syndromes appeared immediately after the injection and disappeared within 3 min. The changes in time course of the behaviour induced by tryptamine were consistent with those of the levels of tryptamine in the brain. Pretreatment with p-chlorophenylalanine, a depleter of 5-hydroxytryptamine (5-HT), failed to alter the effects of tryptamine on head-weaving or hindlimb abduction but did result in head-twitches which were never seen after tryptamine alone. Metergoline strongly antagonized the behavior induced by tryptamine. Pirenperone and haloperidol inhibited the behavioural syndrome, antagonizing the head-weaving in particular. alpha-Methyl-p-tyrosine, a depleter of dopamine, reduced the head-weaving without affecting the hindlimb abduction. These results indicate that the 5-HT syndrome induced by intravenous administration of tryptamine is due to the direct effect of tryptamine on the 5-HT receptor. Tryptamine-induced behaviour, especially head-weaving, seems to be linked with dopaminergic neurones.

Pharmacological analysis of the variation in behavioural responses to tryptamine in five strains of mice

The effects of tryptamine on behaviour were studied in five strains of mice. There were significant strain differences in the intensity of the 5-HT syndrome (head weaving and hindlimb abduction) and head twitch responses. The intensity of the 5-HT syndrome correlated significantly with the brain tryptamine content, although the occurrence of head twitch was unrelated. The 5-HT2 receptor antagonist, ketanserin, antagonized the head twitch responses elicited by tryptamine without affecting the head weaving or hindlimb abduction. Metergoline, an antagonist of both the 5-HT1 and 5-HT2 receptors, strongly inhibited both the 5-HT syndrome and the head twitch responses in all five strains. [3H]5-HT and [3H]ketanserin binding in the frontal cortex of the five strains of mice was also studied. The number of [3H]5-HT binding sites did not differ among the five strains of mice although there was a noticeable difference in the number of [3H]ketanserin binding sites. These results suggest that the 5-HT syndrome and the head twitch responses induced by tryptamine are linked separately with the 5-HT1 and 5-HT2 receptors, respectively. The strain differences in the tryptamine-induced 5-HT syndrome can be explained by the different levels of brain tryptamine. The differences in the head twitch responses in the mice are probably derived from the differences in the 5-HT2 receptor binding sites in the brain and the content of brain tryptamine.

The activation of serotonin receptors by tryptamine induces hyperinsulinemia in mice.

The effects of tryptamine on serum insulin levels were investigated. Tryptamine induced an apparent increase in serum insulin levels in mice. The elevation in insulin elicited by tryptamine was potently antagonized by the 5-HT1 and 5-HT2 receptor antagonist, methysergide, but partially reduced by the 5-HT2 receptor antagonist, ketanserin. However, the 5-HT3 receptor antagonist, ICS 205-930, was without effect. These results indicate that both 5-HT1 and 5-HT2 receptors are involved in the tryptamine-induced increase in insulin levels.

Effects of tryptamine on plasma glucagon levels in mice.

Our previous study indicated that tryptamine induces a dose-related incresae in plasma glucagon levels of mice and that this effect is mediated by the peripheral serotonin2 (5-HT2) receptor. The present paper further investigated the involvement of serotonergic and catecholaminergic systems in hyperglucagonemia elicited by tryptamine. An inhibitor of 5-HT synthesis, p-chlorophenylalanine, did not affect tryptamine-induced increases in plasma glucagon levels. Tryptamine-induced hyperglucagonemia was not inhibited by adrenalectomy or by an inhibition of catecholamine synthesis by α-methyl-p-tyrosine. These findings indicate that tryptamine-induced hyperglucagonemia is elicited by its direct activation of 5-HT2 receptors and is not mediated by levels of endogenous 5-HT and catecholamines. The results further suggest that the peripheral 5-HT2 receptor has a possible role in the release of glucagon.

The involvement of insulin in tryptamine-induced hypoglycemia in mice

The effects of tryptamine on plasma glucose and serum insulin levels were studied in mice. Tryptamine elicited dose-dependent hypoglycemia and hyperinsulinemia in intact mice. In streptozotocin-diabetic mice, tryptamine did not change plasma glucose nor serum insulin levels. Tryptamine significantly inhibited glucose-induced hyperglycemia and enhanced insulin release elicited by glucose. These results indicate that tryptamine-induced hypoglycemia is brought on by its releasing effects of insulin.

The hypoglycemic effects of tryptamine in mice: mediation by 5-HT receptors

The effects of tryptamine on blood glucose levels were studied. Tryptamine induced significant hypoglycemia in mice. The hypoglycemia elicited by tryptamine was strongly antagonized by methysergide, an antagonist of both 5-HT1 and 5-HT2 receptors. A 5-HT2 receptor antagonist, ketanserin, partially inhibited the tryptamine-induced hypoglycemia. These results suggest that tryptamine-induced hypoglycemia is mediated by 5-HT1 and 5-HT2 receptors.