Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antinociceptive effects of the 5-HT1A agonists buspirone [3 mg/kg intraperitoneally (i.p.)], gepirone (3-6 mg/kg i.p.), and 8-OH-DPAT [3-5 mg/kg i.p.; 1-3 micrograms per mouse intracerebroventricularly (i.c.v.)] were examined in mice by using the hot-plate (thermal stimulus) and abdominal constriction (chemical stimulus) tests. Buspirone, gepirone, and 8-OH-DPAT produced significant antinociception, which was prevented by atropine (5 mg/kg i.p.), the ACh depletor hemicholinium-3 (1 microgram per mouse i.c.v.), and the 5-HT1A antagonist NAN 190 (0.5 microgram per mouse i.c.v.), but not by naloxone (1 mg/kg i.p.), the GABAB antagonist CGP 35348 (100 mg/kg i.p.), and pertussis toxin (0.25 microgram per mouse i.c.v.). NAN 190 which totally antagonized buspirone, gepirone, and 8-OH-DPAT antinociception, did not modify the analgesic effect of morphine (5 mg/kg subcutaneously). In the antinociceptive dose range, none of the 5HT1A agonists impaired mouse performance evaluated by rota-rod and hole board tests. On the basis of these data, it can be postulated that buspirone, gepirone, and 8-OH-DPAT exert an antinociceptive effect mediated by a central amplification of cholinergic transmission.
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PMID:5-HT1A agonists induce central cholinergic antinociception. 925 13

The effects of treatment with anxiogenic or anxiolytic agents and exposure to acute restraint stress on emotional behavior in mice were examined using an automatic hole-board apparatus. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e., total locomotor activity, numbers and duration of rearing and head-dipping, and latency to the first head-dipping. The typical benzodiazepine anxiolytics diazepam (0.05-0.5 mg/kg, i.p.) and chlordiazepoxide (0.5-4 mg/kg, i.p.) dose-dependently increased the number and duration of head-dips at doses that did not produce sedation. In contrast with these anxiolytics, the typical anxiogenic drugs N-methyl-beta-carboline-3-carboxamide (FG7142, 0.125-10 mg/kg, i.p.) and methyl-beta-carboline-3-carboxylate (beta-CCM, 0.1-2 mg/kg, i.p.) decreased both the number and duration of head-dips, and increased the latency to head-dipping. Moreover, decreases in the number and duration of head-dips, and an increase in the latency to head-dipping, were also observed in animals that were exposed to acute restraint stress. These effects of acute restraint stress were suppressed by treatment with diazepam at a dose that alone did not produce significant behavioral effects (0.1 mg/kg, i.p.). In addition, non-benzodiazepine anxiolytic flesinoxan (0.1 mg/kg, i.p.), a 5-HT1A receptor agonist, also had an effect on the restraint stress-induced decrease in head-dipping behavior. The present study shows that the changes in several exploratory behaviors could be objectively measured using our automatic hole-board apparatus. Therefore, this system can serve as a useful tool for evaluating the changes in various emotional states of animals. Moreover, we also found that treatment with anxiolytics or anxiogenics and exposure to acute restraint stress affected head-dipping behavior. These results suggest that changes in head-dipping behavior in the hole-board test may reflect the anxiogenic and/or anxiolytic state of animals.
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PMID:Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. 968 10

It has been recently suggested that the central serotonin (5-HT) nervous system may be involved in the modulation of anxiety. Especially, the possible importance of 5-HT1A receptors in anxiety was raised by evidence that the anxiolytic properties of 5-HT1A-receptor agonists have now been confirmed in clinical studies. On the other hand, in preclinical studies using various animal models of anxiety, these novel agents tend to have weak and/or variable effects in some paradigms used to detect the anxiolytic activities of benzodiazepines. These differential patterns of drug effects within various models promote the concept of "multiplicity of anxiety". Recently, a new experimental model called the T-maze was developed in attempts to analyze a different type of anxiety; i.e., conditioned fear and unconditioned fear response. The results of a series of behavioral studies using the T-maze test suggest that distinct 5-HT pathways may modulate the different classes of anxiety. In our recent studies using the hole-board test, apparent differential behavioral effects between benzodiazepine anxiolytics and 5-HT1A agonists on emotionality of stressed mice were also observed. These results suggest that benzodiazepine or 5-HT1A receptors may play a different role in modulating emotionality. These studies may provide new information to investigate the pathophysiological characteristics of various types of anxiety disorders and to develop novel therapeutic agents.
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PMID:[Multiplicity of anxiety and serotonin nervous system]. 1087 13

The effect on memory processes of modulation of 5-HT1A receptor subtype was investigated in the mouse passive avoidance test. The administration of 5-HT1A-receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-2-phthalimmido)butyl]piperazine) and WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide) produced a dose-dependent amnesic effect comparable to that obtained with the well-known amnesic agents scopolamine and dicyclomine. Pretreatment with the 5-HT1A-receptor agonists 8-OH-DPAT ((+/-)-8-hydroxy-dipropylaminotetralin) and 5-CT (5-carboxamidotryptamine) dose-dependently prevented the amnesia induced by 5-HT1A antagonists, scopolamine, dicyclomine and exposure to an hypoxic environment. The antiamnesic effect exerted by 5-HT1A-receptor agonists was comparable to that produced by the nootropic drug piracetam and cholinesterase inhibitor physostigmine. At effective doses, neither 5-HT1A-receptor agonists nor 5-HT1A-receptor antagonists produced any impairment of mouse motor coordination (rota-rod test), spontaneous motility (Animex apparatus) and inspection activity (hole board). These results indicate that modulation of 5-HT1A-receptors appears to play an important role in the regulation of cognitive processes.
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PMID:Role of 5-HT1A receptors in a mouse passive avoidance paradigm. 1120 14

In the present study, the n-hexane extract of Myristica fragrans (MF) seeds, acetone-insoluble part of the n-hexane extract (AIMF) and trimyristin (TM) were assessed for their anxiogenic activity. The MF (10 and 30 mg/kg), AIMF (30, 100, and 300 mg/kg), and TM (10, 30, and 100 mg/kg) administered intraperitoneally exhibited anxiogenic activity in elevated plus-maze (EPM) paradigm. The open-field test and hole-board test were also used to assess anxiogenic activity of AIMF and TM. In the EPM test, MF, AIMF, and TM decreased the time spent by mice in the open arm and the entries in the open arm. Further, the effect of diazepam (1 mg/kg i.p.), serotonin 5-HT3 receptor antagonist, ondansetron (1 mg/kg i.p.), and 5-HT1A receptor agonist, buspirone (1 mg/kg i.p.), on the occupancy in open arm and entries in open arm was significantly reduced by TM. In the open-field test, AIMF as well as TM reduced the number of rearing and locomotion. Both TM and AIMF reduced the number of head pock in the hole-board test. Inhibition of anxiolytic activity of ondansetron (5-HT3 receptor antagonist), buspirone (5-HT1A receptor agonist), and diazepam [acting on gamma-aminobutyric acid (GABAA) receptor] suggests a nonspecific anxiogenic activity of TM and also a link between 5-HT and GABA systems in the anxiogenic activity of TM.
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PMID:Anxiogenic activity of Myristica fragrans seeds. 1181 28

S-100beta is an astroglial-derived protein, which plays a role in brain development and maintenance, and is known to play a specific role in the regulation of growth of the serotonergic neuronal system. In humans, the gene for S-100beta is found on chromosome 21, within the region that is considered important for the phenotype of Down syndrome (DS). Thus, we have been studying a model of DS, the S-100beta transgenic mouse. In the current study, we have examined anxiety and responses to novelty in adolescent (60-90 days) animals, at a time when we have shown the animals to be relatively lacking in serotonin innervation, compared to their CD-1 nontransgenic controls. In a test for approach/avoidance, the light/dark test, the S-100beta transgenic mice animals showed no differences from control CD-1 mice. However, in the hole-board test for exploratory behavior, the S-100beta animals were found to be less responsive to the inhibiting effects of the serotonin receptor 5-HT1A agonist, buspirone. Three tests were used to measure response to novelty. In the open field, the S-100beta animals showed greater activity longer than the control animals, and in the Y-maze test, the S-100beta animals spent more time in the novel arm. In a test for novelty-induced gnawing, the S-100beta animals were also more active than control animals. All of these suggest that the S-100beta transgenic mice are slower to habituate to novelty than control animals. Finally, we tested the animals in a new procedure that we are proposing as a test for harm avoidance. In this apparatus, the S-100beta animals showed more approaches to a novel and potentially harmful object than the control mice did. These results are discussed in reference to the known lack of serotonin in the animals, and to the behavioral phenotype of DS.
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PMID:Harm avoidance, anxiety, and response to novelty in the adolescent S-100beta transgenic mouse: role of serotonin and relevance to Down syndrome. 1288 77

The effects of nociceptin on the exploratory behavior of mice were examined using an automatic hole-board apparatus. A low dose of nociceptin (0.01 nmol, i.c.v.) had an anxiolytic effect, as reflected by an increase in head-dipping behavior. However, high doses of nociceptin (1-5 nmol, i.c.v.) produced a dose-dependent anxiogenic effect, as reflected by a decrease in head-dipping behavior. Both the anxiolytic and anxiogenic effects of nociceptin were antagonized by nocistatin, an opioid receptor-like 1 (ORL1) receptor antagonist. Although a low dose (0.01 nmol, i.c.v.) of nociceptin significantly increased the rate of serotonin (5-hyroxytryptamine, 5-HT) turnover in the hippocampus, a high dose (5 nmol, i.c.v.) of nociceptin significantly decreased this turnover in the amygdala. Furthermore, the anxiolytic effect of nociceptin at a low dose was antagonized by N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide 3HCl (WAY100635), a 5-HT1A receptor antagonist. On the other hand, the anxiogenic effect of nociceptin at a high dose was antagonized by R(+)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT), a 5-HT1A receptor agonist. In conclusion, the results of this study suggest that nociceptin has dose-related anxiolytic and anxiogenic effects as a result of the activation of ORL1 receptors. The present results also suggest that a low dose of nociceptin has an anxiolytic effect via the activation of 5-HT ergic function in the hippocampus, while a high dose of nociceptin has an anxiogenic effect via the inhibition of 5-HT ergic function in the amygdala.
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PMID:Effects of nociceptin on the exploratory behavior of mice in the hole-board test. 1506 58

We examined the effect of Vilazodone, a selective serotonin reuptake inhibitor (SSRI) and serotonin 1A (5-HT(1A)) receptor agonist [Bartoszyk, G.D., Hegenbart, R., Ziegler, H., 1997. EMD 68843, a serotonin reuptake inhibitor with selective presynaptic 5-HT1A receptor agonistic properties. Eur. J. Pharmacol. 322, 147-153.], on change in affect following predator stress. Vilazodone and vehicle injection (intraperitoneal) occurred either 10 min after predator stress (prophylactic testing), or 90 min prior to behavioral testing for the effects of predator stress (therapeutic testing). Predator stress involved unprotected exposure of rats to a domestic cat. Behavioral effects of stress were evaluated with hole board, plus-maze, and acoustic startle tests 1 week after stress. Predator stress increased anxiety-like behavior in the plus-maze and elevated response to acoustic startle. In prophylactic testing, Vilazodone affected stress potentiation of startle at doses above 5 mg/kg. Vilazodone increased stress elevation of startle at 10 mg/kg. Higher doses of Vilazodone (20 and 40 mg/kg) blocked stress potentiation of startle. In contrast, Vilazodone had no effect on stress potentiation of anxiety in the plus-maze. In therapeutic testing, Vilazodone increased stress elevation of startle at all doses. In contrast, therapeutic Vilazodone had no effect on stress potentiation of anxiety in the plus-maze. Taken together, the data suggest a prophylactic potential for Vilazodone in the treatment of changes in hypervigilance following severe stress.
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PMID:Effects of systemic injections of vilazodone, a selective serotonin reuptake inhibitor and serotonin 1A receptor agonist, on anxiety induced by predator stress in rats. 1550 23

The aim of the present study was to examine the effect of yokukansan, a traditional Japanese herbal medicine that is composed of Atractylodis lanceae Rhizoma, Poria, Cnidii Rhizoma, Uncariae Uncis cum Ramulus, Angelicae Radix, Bupleuri Radix and Glycyrrhizae Radix, on the emotional abnormality induced by maladaptation to stress in mice. Mice were exposed to repeated restraint stress for 60 or 240 min/day for 14 days. From the 3rd day of stress exposure, mice were given yokukansan orally (p.o.) or the 5-HT1A receptor agonist flesinoxan intraperitoneally (i.p.) immediately after the daily exposure to restraint stress. After the final exposure to restraint stress, the emotionality of mice was evaluated using an automatic hole-board apparatus. A single exposure to restraint stress for 60 min induced a decrease in head-dipping behavior in the hole-board test. This emotional stress response disappeared in mice that had been exposed to repeated restraint stress for 60 min/day for 14 days, which confirmed the development of stress adaptation. In contrast, mice that were exposed to restraint stress for 240 min/day for 14 days did not develop this stress adaptation, and still showed a decrease in head-dipping behavior. The decreased emotionality observed in stress-maladaptive mice was significantly recovered by chronic treatment with yokukansan (1000 mg/kg, p.o.) as well as flesinoxan (0.25 and 0.5 mg/kg, i.p.) immediately after daily exposure to stress. These findings suggest that yokukansan may have a beneficial effect on stress adaptation and alleviate the emotional abnormality under conditions of excessive stress.
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PMID:Yokukansan, a traditional Japanese herbal medicine, alleviates the emotional abnormality induced by maladaptation to stress in mice. 2412 19