Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The behavioural effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in mice. 297 71

Alaproclate (10-60 mg/kg) injected i.p. into male mice potentiated and prolonged the oxotremorine and physostigmine-induced tremor in a dose-dependent manner. Atropine completely blocked the tremor caused by oxotremorine or physostigmine both in the presence and absence of alaproclate. Pretreatment with the 5-HT receptor antagonist metitepine completely blocked the enhancement of oxotremorine-induced tremor caused by alaproclate. Biochemical studies indicated that the above effects cannot be explained by assuming that alaproclate a) acts as a cholinergic agonist, b) inhibits the acetylcholine esterase, c) interferes with choline uptake or acetylcholine synthesis, or d) directly potentiates the release of acetylcholine. In ligand binding studies alaproclate was found to be a weak competitive inhibitor of muscarinic antagonist binding to membranes from the rat cerebral cortex, rat striatum, human cerebral cortex and human striatum. (Ki approximately 28-40 microM in all four tissues). The present results suggest that alaproclate may potentiate muscarinic responses by a mechanism involving serotonergic receptor mechanisms rather than by a direct interaction with the muscarinic cholinergic receptors.
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PMID:In vivo and in vitro studies on the potentiation of muscarinic receptor stimulation by alaproclate, a selective 5-HT uptake blocker. 298 30

Brain 5-HT receptors are reported to play an important role in the therapeutic effect of Li in manic-depressive illness. In the present study we examined the effect of Li on 5-HT syndrome which is postulated to be the physiological response of 5-HT1 receptors. Intraperitoneal injection of the 5-HT receptor agonist 5-MeODMT elicited 5-HT syndrome in a dose-dependent manner. Then the incidence of 5-HT syndrome elicited by 2 mg/kg of 5-MeODMT was measured in animals under long-term Li treatment. Four out of six abnormal behaviors of the 5-HT syndrome, i.e. forepaw treading, resting tremor, rigidity, and head weaving, were significantly increased by the 9-day treatment with Li. On the 17th day of Li treatment, the incidence of all six behaviors, including hindlimb abduction and straub tail, were significantly enhanced. This Li-induced supersensitivity of 5-HT1 receptor-mediated behaviors inconsistent with the previous reports of the down-regulation of 5-HT1 receptors measured by receptor binding assay. The reason for this discrepancy is obscure. Further examination of the effect of Li on the signal-transduction system from the receptor to the behavior will be necessary.
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PMID:[Effect of long-term lithium treatment on serotonin syndrome in rats]. 309 11

The effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on head shaking behavior induced by L-5-HTP and behavioral symptoms induced with 5-methoxy-N,N,-dimethyltryptamine (5-MeODMT) in rats was evaluated. Both drugs dose-dependently reduced L-5-HTP-induced head shaking but were at least 600 times less potent than pirenperone and ketanserin and at least 50 times less potent than methysergide. ICS 205-930 and MDL 72222 were more than 1000 times less potent than pirenperone or methysergide and 100 times less potent than ketanserin in blocking 5-MeODMT-induced forepaw treading and tremor. Since it appears that head shakes induced by L-5-HTP are mediated by 5-HT2 receptors, these data suggest that ICS 205-930 and MDL 72222 do not significantly interact with 5-HT2 receptors in the brain. Furthermore, the data suggest that ICS 205-930 and MDL 72222 lack appreciable antagonistic activity at the 5-HT receptor(s) mediating those behavioral effects induced by 5-MeODMT.
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PMID:Effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on 5-HTP-induced head shaking and behavioral symptoms induced by 5-methoxy-N,N,dimethyltryptamine in rats: comparison with some other 5-HT receptor antagonists. 311 4

The responses of male and female rats to drugs causing the behavioural syndrome induced by 5-hydroxytryptamine (5-HT) were compared. Preliminary experiments showed that females had largely similar responses to the releaser of 5-HT, p-chloroamphetamine (PCA) and the 5-HT receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) at different stages of the oestrus cycle. The behavioural responses to 5-MeODMT (with and without the monoamine oxidase inhibitor pargyline) or to p-chloroamphetamine were not significantly different to those of males except for tremor after p-chloroamphetamine which was more marked in the females. However, concentrations of p-chloroamphetamine in brain in these animals, when killed immediately after behavioural recording were greater in the females. When rats, pretreated with the monoamine oxidase inhibitor, pargyline, were given the precursor of 5-HT, tryptophan, the females showed substantially greater hypothermia and larger scores for components of the 5-HT syndrome than the males. This sex difference may have been due to the moderately but significantly higher levels of 5-HT (and possibly tryptamine) in brain attained by the female rats, than by similarly-treated males. The results as a whole therefore suggest that the greater behavioural response of female rats to pargyline and tryptophan reflects a greater effect of this treatment on the synthesis of indoleamines than that occurring in males.
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PMID:5-Hydroxytryptamine-mediated behaviour in male and female rats. 374 24

The intensity of the head-twitch response and the 5-hydroxytryptamine (5-HT) syndrome (tremor, fore-paw treading, head-weaving and hind-limb abduction) was measured in male CFLP mice following IP injection of 5 mg/kg 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The results of separate experiments carried out at 1.5-h intervals throughout the light-dark cycle showed a clear circadian variation in head-twitch, with highest scores mid-light. No circadian variation in the 5-HT syndrome, or in any individual element of it, was observed. Dose-response curves constructed for 5-MeODMT mid-light and mid-dark over the range 2-64 mg/kg IP confirmed the difference in head-twitch response, showing a parallel shift to the right for mid-dark compared to mid-light up to 32 mg/kg. Again, no difference was seen between the two curves for the 5-HT syndrome. Measurement of the time course of behavioural activity following 5-MeODMT failed to show any differences between mid-light and mid-dark, making it unlikely that pharmacokinetic differences account for the observed circadian variation. It is suggested that the demonstration of a circadian rhythm in the head-twitch response and the failure to show any comparable rhythm in the 5-HT syndrome provides further evidence that these behaviours are mediated by different 5-HT receptor subtypes.
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PMID:Circadian variation in behavioural responses to central 5-HT receptor stimulation in the mouse. 392 60

1 The behavioural responses of drugs known to act through central 5-hydroxytryptamine (5-HT) mechanisms have been investigated in rats receiving a neuroleptic (trifluoperazine) in their drinking water for 4 to 6 months.2 5-Hydroxytryptophan (5-HTP) induced 5-HT-dependent behaviours including head bobbing and lateral head weaving, reciprocal forepaw treading, tremor, backward walking, body writhing and ;wet-dog' shakes. In doses of 50 to 150 mg/kg, 5-HTP induced more intense behavioural effects in neuroleptic-treated rats than in the control animals.3 Similarly the putative 5-HT agonist, quipazine (1 to 20 mg/kg) and the 5-HT releasing drug, fenfluramine (5 to 20 mg/kg), both induced significantly greater motor responses in the chronically neuroleptic-treated rats.4 A 5-HT uptake inhibitor (femoxetine, 2.5 to 10 mg/kg) had little behavioural effect in either control or trifluoperazine-treated rats.5 Total specific high-affinity binding of radiolabelled 5-HT was significantly increased in crude membrane fractions prepared from the cortex, striatum and substantia nigra of neuroleptic-treated rats compared to control animals.6 High-affinity uptake of radiolabelled 5-HT into striatal slices was similar in experimental and control animals.7 Behavioural and biochemical data would indicate that postsynaptic 5-HT mechanisms are enhanced in rats treated chronically with trifluoperazine. Chronic neuroleptic therapy may thereby induce cerebral 5-HT receptor supersensitivity in addition to the well-documented cerebral dopamine receptor supersensitivity.
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PMID:Increased central 5-hydroxytryptamine receptor mechanisms in rats after chronic neuroleptic treatment. 611 11

The present study investigated the involvement of presynaptic serotonergic mechanisms in the sleep suppressant action of fenfluramine, an indirect serotonin (5-HT) receptor agonist. Rats implanted with cerebrocortical and dorsal neck muscle electrodes were pretreated with either fluoxetine, an inhibitor of 5-HT uptake, or p-chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis. Animals were continuously monitored by the EEG for 12 hr after an i.p. injection of 5 mg/kg of dl-fenfluramine hydrochloride. Pretreatment with fluoxetine failed to antagonize the fenfluramine-induced suppression of slow-wave sleep and rapid-eye-movement sleep. However, chemical analyses showed that fluoxetine pretreatment completely prevented the depletion of brain 5-HT produced by fenfluramine, suggesting that fenfluramine did not gain entry into serotonergic neurons. Depletion of brain 5-HT by PCPA also failed to antagonize the sleep suppression caused by fenfluramine as well as that observed after administration of quipazine, a direct 5-HT receptor stimulant. Because administration of fenfluramine to PCPA-pretreated rats produced no additional depletion of 5-HT, it appears that 5-HT was no longer available for release by fenfluramine in these animals. Furthermore, neither pretreatment with fluoxetine nor PCPA antagonized the head-shaking induced by fenfluramine, a behavior associated with activation of central 5-HT receptors. These data indicate that the suppression of sleep produced by fenfluramine is not mediated through release of 5-HT as brain 5-HT concentrations were not related to the behavioral effects of the drug. The sleep suppressant action of fenfluramine may therefore result from a direct action of the drug on postsynaptic 5-HT receptors.
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PMID:Sleep suppressant action of fenfluramine in rats. II. Evidence against the involvement of presynaptic serotonergic mechanism. 622 35

The effects of fenfluramine, an indirect serotonin (5-HT) receptor agonist, on sleep and brain indole- and catecholamines were examined in rats. Animals implanted with cerebrocortical and dorsal neck muscle electrodes were continuously monitored by the EEG for 12 hr after i.p. injections of dl-fenfluramine hydrochloride (1, 5 and 10 mg/kg). Fenfluramine produced a dose-dependent suppression of both slow-wave sleep (SWS) and rapid-eye-movement sleep (REMS). Accompanying these effects was a dose-dependent increase in head-shaking, a behavior associated with activation of central 5-HT receptors. The incidence of head-shaking was inversely related to SWS and REMS time. At doses which significantly suppressed sleep (5 and 10 mg/kg), fenfluramine lowered whole brain 5-HT and 5-hydroxyindoleacetic acid concentrations without affecting brain catecholamines. Pretreatment with metergoline (2.5 and 5.0 mg/kg i.p.), a 5-HT receptor antagonist, 1 hr before the administration of fenfluramine (5 mg/kg) blocked the fenfluramine-induced suppression of SWS in a dose-dependent manner and prevented head-shaking behavior, but failed to prevent the suppression of REMS. In contrast, pretreatment with alpha-flupenthixol (0.2 mg/kg i.p.), a dopamine receptor antagonist, had no effect on the suppression of sleep and the stimulation of head-shaking behavior produced by fenfluramine. These data suggest that the suppression of SWS but not of REMS by fenfluramine is mediated by activation of the serotonergic system. The increase in serotonergic activity produced by fenfluramine may result from the drug-induced release of 5-HT with subsequent stimulation of postsynaptic 5-HT receptors. These findings are consistent with our hypothesis that pharmacological stimulation of 5-HT receptors suppresses sleep in the rat.
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PMID:Sleep suppressant action of fenfluramine in rats. I. Relation to postsynaptic serotonergic stimulation. 668 11

Intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) (5 micrograms) to mice selectively lesioned descending serotonergic pathways, reducing spinal levels of 5-hydroxytryptamine (5-HT) by 80%, without significantly changing the levels of noradrenaline. Increased sensitivity to noxious stimulation, as measured by the tail-flick and hot-plate tests, was observed 2 days after injection of 5,6-DHT. The tail-flick latencies returned to normal on day 6, but were again reduced by administration of the 5-HT receptor blocker metergoline, suggesting that the normalization process involved compensatory mechanisms in the remaining 5-HT system. In the hot-plate test, the latencies both to shaking or kicking of a hindpaw (kick) and to hindpaw lick were recorded, but the time course for the changes of these two responses was found to be different. The latencies to hindpaw lick were normalized within 2 weeks, whereas the hindpaw kick latencies remained reduced throughout the 21 day observation period.
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PMID:Changes in nociception after intrathecal administration of 5,6-dihydroxytryptamine in mice. 668 57


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