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

Previous studies have established that a complex behavioral syndrome--consisting of tremor, rigidity, hindlimb abduction. Straub tail, lateral head weaving and reciprocal forepaw treading--is a specific reflection of the activity of central serotonin receptors. This syndrome was utilized in the present study to test for supersensitivity in the central serotonergic system. Specific destruction of central serotonin nerve terminals by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT, 50 mug) in adult male rats pretreated with a catecholamine uptake blocking agent resulted in marked supersensitivity to serotonin precursors and agonists. The greatest degree of supersensitivity was observed in response to L-5-hydroxytryptophan, for which the ED50 for elicitation of the syndrome was 20% of the value for control rats. A lesser degree of supersensitivity was seen in response to L-tryptophan (following monoamine oxidase inhibition) and the direct-acting serotonin agonist, 5-methoxy-N,N-dimethyltryptamine, for which the ED50 was approximately 50% of the control value in both cases. Supersensitivity begins to develop within 24 hours and is relatively complete by 96 hours after 5,7-DHT. A marked subsensitivity to the serotonin releasing agent, fenfluramine, was found in 5,7-DHT-treated rats. In contrast to the marked supersensitivity to serotonin precursors and agonists which occurs following 5,7-DHT, chronic administration of a serotonin synthesis inhibitor, p-chlorophenylalanine (400 mg/kg every 3 days for a total of 24 days), did not produce supersensitivity to L-5-hydroxytryptophan or 5-methoxy-N,N-dimethyltryptamine. Possible pre- and postsynaptic mechanisms for the development of supersensitivity are discussed.
 ...
PMID:Behavioral evidence for supersensitivity following destruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine. 13 25

The serotonin precursor, 5-hydroxytryptophan (5-HTP), can induce a behavioral syndrome characterized by rigidity, splayed feet, tremor, head weaving, salivation and forepaw treading. This response to 5-HTP was markedly potentiated in adult rats treated intracisternally with 5,7-dihydroxytryptamine (5,7-DHT) during development. Prevention of the 5,7-DHT-induced reduction of brain norepinephrine with pargyline or desipramine did not diminish the potentiation of 5-HTP, suggesting that noradrenergic fibers are not contributing to the altered 5-HTP response. It was also found that treatments with 5,7-DHT potentiated the release of prolactin and the disruption of responding in a fixed-ratio operant task induced by 5-HTP. Other experiments indicated that 5,7-DHT treatments potentiated 5-HTP without affecting the action of L-dihydroxyphenylalanine. In addition, administration of the decarboxylase inhibitor, R0-4-4602, at a dose that inhibits enzyme activity in brain, blocked the 5-HTP-induced behavioral syndrome in 5,7-DHT-treated rats, indicating that 5-HTP must be converted to serotonin for 5-HTP to alter behavior. Thus, the present studies indicate that destruction of serotonergic fibers during development can produce permanent changes in central serotonergic mechanisms.
 ...
PMID:Behavioral and prolactin responses to 5-hydroxytryptophan in rats treated during development with 5,7-dihydroxytryptamine. 30 87

Intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) following treatment with desmethylimipramine induced development of behavioral supersensitivity to the intraperitoneally administered serotonin precursor 5-hydroxytryptophan (5-HTP) in the mouse. This behavioral syndrome, characterized by tremor and muscle twitches (myoclonus), showed a clear dose-response relationship with 5,7-DHT as well as with 5-HTP. Mice lesioned with a low dose of 5,7-DHT (20 micrograms) or a placebo were treated repeatedly with a protein synthesis inhibitor, sycloheximide (45 mg/kg, s.c., every 12 h for up to 10 days). This treatment resulted in a reversible decrease of cerebral protein synthesis varying between 70 and 20% with time between treatments. The myoclonic response to 5-HTP in animals pretreated with 5,7-DHT and by cycloheximide showed a decrease in intensity within 24 h when evaluated quantitatively by an electronic activity monitor, the results of which were confirmed by direct observation. Cycloheximide also exerted a similar, though smaller, effect following full development of sensitivity to 5-HTP over 10 days. These effects may de mediated by inhibition of rapidly turning over serotonin receptor proteins, although their interpretation is somewhat obscured by possible toxic effects of cycloheximide.
 ...
PMID:Inhibition of 5,7-dihydroxytryptamine-induced supersensitivity to 5-hydroxytryptophan in mice by treatment with cycloheximide. 31 Mar 31

The administration of veratramine produced generalized tremor, myoclonus, hindlimb abduction, backward gait and Straub tail, similar to the "5-hydroxytryptamine (5-HT) syndrome", in mice. Pretreatment with metergoline, methysergide, mainserin or cyproheptadine ameliorated veratramine-induced myoclonus and tremor. For suppression of other symptoms, mianserin and cyproheptadine were effective. Metergoline improved hindlimb abduction and Straub tail, but did not inhibit backward gait. Methysergide was ineffective for the remaining symptoms. 5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) enhanced all these symptoms except for Straub tail. 8-Hydroxy-2-[di-n-propylamino] tetralin hydrobromide (8-OH-DPAT) augmented tremor, hindlimb abduction and backward gait, but did not influence myoclonus and Straub tail. 5-Methoxy-3[1,2,3,6-tetrahydropyridin-4-yl] 1H-indole (RU 24969) did not modify the symptoms. Destruction of 5-HT neurons using 5,6-dihydroxytryptamine (5,6-DHT) resulted in suppression of the syndrome. The denervation supersensitivity caused by 5,6-DHT did not increase the response to veratramine. These findings indicate that part of the site of action of veratramine may be the presynaptic 5-HT neurons.
 ...
PMID:Veratramine-induced behavior associated with serotonergic hyperfunction in mice. 171 Feb 97

To study the involvement of serotonin (5-HT) receptor subtypes in behavioral supersensitivity following neonatal 5,7-dihydroxytryptamine (5,7-DHT) lesions, we measured acute behavioral responses to a single dose of selective 5-HT1A (8-OH-DPAT) or 5-HT2,1C (DOI) agonist compared to 5-hydroxytryptophan (5-HTP) in rats injected with 5,7-DHT intraperitoneally or intracisternally 14 weeks earlier. Only intraperitoneal 5,7-DHT injection resulted in brainstem 5-HT hyperinnervation, but cortical 5-HT depletions were also less. Effects of DOI, such as shaking behavior and forepaw myoclonus, were enhanced by 5,7-DHT lesions made intracisternally not intraperitoneally, whereas 8-OH-DPAT-evoked behaviors, such as forepaw myoclonus and head weaving, were enhanced more by the intraperitoneal route. The main consequence of intraperitoneal compared to intracisternal 5,7-DHT injection on supersensitivity to 5-HT agonists was increased presynaptic 5-HT1A responses and decreased 5-HT2,1C responses. In contrast, 5-HTP evoked more shaking behavior and less of the serotonin syndrome with the intraperitoneal compared to the intracisternal route of 5,7-DHT injection. Behavioral supersensitivity to 5-HTP, which was attributable to 5-HT1A, 5-HT2,1C, and possibly to other 5-HT receptors, was orders of magnitude greater than that elicited by direct receptor agonists and more clearly differentiated between rats with 5,7-DHT lesions and their controls, and between routes of 5,7-DHT injections, than responses to 5-HT agonists at the dose studied. 5,7-DHT induced dysregulation of 5-HT receptors, including both presynaptic and postsynaptic changes and altered interactions between receptor subtypes, better explains these data than postsynaptic changes alone.
 ...
PMID:The functional significance of neonatal 5,7-dihydroxytryptamine lesions in the rat: response to selective 5-HT1A and 5-HT2,1C agonists. 214 15

Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5-HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences.
 ...
PMID:Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5-hydroxytryptophan in the rat. 258 10

There have been few previous studies of the functional significance of 5,7-dihydroxytryptamine (5,7-DHT) lesions made in neonatal rats. To study the role of serotonin (5-HT) in recovery of function, rat pups and adult rats were injected intracisternally with 5,7-DHT or saline and challenged acutely with the 5-HT precursor 5-hydroxytryptophan (5-HTP) 4 weeks later as a test of behavioral supersensitivity. Compared to 5,7-DHT lesions in adults, neonatal lesions induced significantly greater 5-HT depletions in brainstem, but 5-HT depletions in other regions were not significantly different in the two groups. Rats with early 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP, consisting of all the component myoclonic-serotonergic behaviors seen in rats with 5,7-DHT lesions made as adults. However, there was significantly less 5-HTP-evoked head weaving, truncal myoclonus and shaking behavior in rats treated with 5,7-DHT as neonates. Body weight was reduced both in rats with early and late 5,7-DHT lesions, but reduction persisted in rats with early lesions. These data indicate overall similarity with some differences between neurochemical and behavioral effects of early and late 5,7-DHT lesions made by the intracisternal route. They suggest that recovery mechanisms did not occur or failed to reverse the neurochemical or behavioral consequences of early 5,7-DHT lesions.
 ...
PMID:Intracisternal 5,7-dihydroxytryptamine lesions in neonatal and adult rats: comparison of response to 5-hydroxytryptophan. 278 68

1. The relationship of the behavioral syndromes induced by the co-transmitters thyrotropin releasing hormone (TRH) and serotonin (5-HT) has not been previously studied with drugs selective for 5-HT receptor subtypes. 2. Both the TRH analog MK-771 (in naive rats) and 5-hydroxytryptophan (in rats with 5,7-dihydroxytryptamine [DHT] lesions) evoked reciprocal forepaw tapping, Straub tail, hunching, hindlimb abduction, and shaking behavior. Sniffing and rearing were features of the MK-771 but not the 5-HT syndrome. 3. 5-HTP potentiated MK-771-induced hyperthermia. 4. MK-771 evoked two types of shaking behavior, head shakes (HS) and wet-dog shakes (WDS). Neither independently was dose-related, unlike total shaking behaviors. 5. MK-771-induced shaking behavior was pharmacologically dissociated from other MK-771-evoked behaviors. A 5-HT1A agonist (8-OH-DPAT) blocked WDS, but like putative 5-HT1B (RU 24969) and 5-HT2 (DOI) agonists and the 5-HT antagonists methysergide (non-selective), ritanserin (5-HT2 selective), and l-propranolol (5-HT1 selective), it did not block other antagonists behavioural effects of MK-771. 6. Ipsapirone, a 5-HT1A-active drug purported both as an agonist and as an antagonist, inhibited MK-771-evoked WDS, like 8-OH-DPAT, but did not induce the serotonin syndrome, unlike 8-OH-DPAT. 7. DHT-treated rats were behaviorally supersensitive to 10 mg/kg MK-771 as indicated by a significantly shortened latency of onset of WDS and greater frequency of abnormal forepaw movements. The same rats were also supersensitive to 50 mg/kg 5-HTP to a significantly greater degree. 8. These data suggest behavioral relatedness of the TRH and 5-HT syndromes, but distinctive pharmacologic features and presumed mechanisms of action.
 ...
PMID:The comparative pharmacology of the behavioral syndromes induced by TRH and by 5-HT in the rat. 289 33

Ontogenic evolution of behavioural and electrophysiological responses to the serotonergic agents, quipazine and harmaline, was studied in the maturing rabbit in normal and pretreated conditions. As regards behavioural effects, tremor induced by quipazine was present from the first postnatal day and was antagonized by methysergide, but not by p-chlorophenylalanine (PCPA) or pretreatment with 5,7-dihydroxytryptamine (5,7-DHT). In contrast, tremor induced by harmaline could not be elicited before the second postnatal week and was partially antagonized by methysergide and 5,7-DHT, but not by PCPA. Electrophysiological studies of cell activity in the inferior olivary nucleus revealed a similar dependency on age since rhythmic activation of the inferior olivary nucleus could be registered from the first postnatal day with quipazine and only from the 8th postnatal day with harmaline; drug interactions with methysergide, PCPA and 5,7-DHT were the same as for the behavioural observations. It is suggested that quipazine directly activates serotonin receptors which are already present at birth, whereas harmaline requires the presence of serotonergic fibres for such activation.
 ...
PMID:Drug-induced activation of the inferior olivary nucleus in young rabbits. Differential effects of harmaline and quipazine. 316 Sep 66

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.
 ...
PMID:Changes in nociception after intrathecal administration of 5,6-dihydroxytryptamine in mice. 668 57


1 2 Next >>