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)

Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defecation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P less than 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of ipsapirone (0.5 and 1 mg/kg, i.p.). However, ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by ipsapirone. However, the ACTH response to CER was significantly (P less than 0.01) inhibited by all doses of ipsapirone and the highest dose of ipsapirone attenuated the renin response. In contrast with the hormonal responses, ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to ipsapirone, while corticosterone and prolactin were the least sensitive to ipsapirone.
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PMID:Comparison of neuroendocrine and behavioral effects of ipsapirone, a 5-HT1A agonist, in three stress paradigms: immobilization, forced swim and conditioned fear. 135 56

The present study investigated whether there is any difference between the effects of benzodiazepine and non-benzodiazepine anxiolytics on agonistic behavior in male mice, using an ethopharmacological technique. Agonistic behavior was evoked using a resident-intruder paradigm. The effects of four doses of the following drugs were assessed in either resident or intruder mice: diazepam (vehicle, 1, 2.5 and 5 mg/kg, p.o.) and tandospirone (vehicle, 2.5, 5 and 10 mg/kg, p.o.). Residents and intruders were drugged on alternate test days, and all animals received different sequences of each of the drug conditions according to a random schedule. The injection-test interval was 30 min. When a resident mice were treated with either diazepam or tandospirone, the frequency of attack bite was suppressed significantly in a dose-dependent manner. When intruder mice were treated with diazepam, attack bites by untreated residents were significantly increased, whereas tandospirone was ineffective. Although diazepam caused a significant decrease in both locomotion and rearing, tandospirone did not cause motor dysfunction. These evidence indicate that tandospirone, a 5-HT1A receptor agonist, has different pharmacological properties from diazepam.
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PMID:[Comparison of the effects of benzodiazepine and non-benzodiazepine anxiolytics on agonistic behavior in male mice]. 135 30

To clarify which 5-HT1A receptors, autoreceptors located in the raphe nuclei or post-synaptic receptors in the forebrain areas receiving a 5-HT input, mediate the anticonflict action of tandospirone (a 5-HT1A receptor-related anxiolytics), the behavioral effects of tandospirone were studied in 5,7-dihydroxytryptamine (5,7-DHT) treated rats. By measuring both monoamines and their metabolite levels and densities of [3H]8-OH-DPAT binding in 5,7-DHT-treated rat brain, we confirmed that pretreatment with 5,7-DHT destroyed 5-HT neurons selectively without affecting postsynaptic 5-HT1A receptors located on the postsynaptic neurons. This selective destruction produced no significant changes in the drinking behavior of rats in either punished or unpunished sessions of the Vogel conflict test. Furthermore, this destruction altered neither the effect of tandospirone on punished responding in this procedure nor the potency of tandospirone to induce a flat body posture in rats, which is known as the "serotonin behavioral syndrome". These results suggested that the anticonflict action of tandospirone may be produced, at least in part, by binding to postsynaptic 5-HT1A receptors and activating them as agonists, and not to 5-HT1A autoreceptors located on the cell bodies of 5-HT neurons.
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PMID:Serotonergic mechanisms in anxiolytic effect of tandospirone in the Vogel conflict test. 135 71

Cognitive activation in conjunction with pharmacological challenge was used to demonstrate neuromodulation in man. Using positron emission tomography (PET), measurements of regional cerebral blood flow were made during the performance of memory tasks, before and after the administration of apomorphine (dopamine agonist), buspirone (5-HT1A partial agonist) or placebo. Drug effects on memory-induced increases in regional cerebral blood flow were assessed, on a voxel-by-voxel basis, using statistical parametric mapping. Increases of regional cerebral blood flow in response to the memory challenge were attenuated by apomorphine in the dorsolateral prefrontal cortex and augmented in the retrosplenial region of the posterior cingulate. Conversely, buspirone attenuated blood flow increases in the retrosplenial region. These interactions between drugs and a cognitive challenge can best be interpreted as neuromodulatory effects.
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PMID:Measuring the neuromodulatory effects of drugs in man with positron emission tomography. 135 45

Tandospirone is a novel non-benzodiazepine compound possessing potent anxiolytic properties in a water lick conflict paradigm in rats and a high affinity for central 5-HT1A receptors. In the present study, tandospirone was evaluated for anxiolytic activity in a modified Geller-Seifter conflict paradigm in rats. Tandospirone produced significant increases in the punished responding at doses of 1.25, 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o., although it decreased unpunished responding at doses of 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o. Likewise, diazepam was also effective after i.p.-administration in this test, and its minimum effective dose was slightly higher than that of tandospirone. This suggests that tandospirone might be as effective in the treatment of anxiety as diazepam. The anticonflict action of tandospirone was not inhibited by Ro-15-1788, a benzodiazepine antagonist, although that of diazepam was completely inhibited. 8-OH-DPAT, a full agonist of 5-HT1A receptors, was also effective in this test with a high potency. Therefore, the possibility exists that the anticonflict action of tandospirone is related to its agonist action on 5-HT1A receptors, not on benzodiazepine receptors.
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PMID:Anticonflict action of tandospirone in a modified Geller-Seifter conflict test in rats. 135 47

At present the dominant position among anti-anxiety medications has changed from meprobamate to the benzodiazepine derivatives. In order to avoid benzodiazepine's (BZ) undesirable side effects such as impairment of psycho-motor function, memory impairment, low dose dependence and withdrawal symptoms, a third generation anxiolytic agent, buspirone, the focus of the aryl-piperazine group of anti-anxiety agents, has been introduced recently. Aryl-piperazine derivatives work as 5-HT1A receptor partial agonists and are known as serotonin normalizers. Therefore, they are expected to have not only an anxiolytic function but also an anti-depressant effect as well. A characteristic of the aryl-piperazine derivatives is that they have no sedative and muscle relaxant effects, and they do not have BZ's undesirable side-effects, especially in regard to withdrawal symptoms. However they have a rather weak anxiolytic action and a slow onset of action. Aryl-piperazine derivatives will not take the place of BZ, but the use of BZ and buspirone as bridge medications, making the most of the strong points of both, can be proposed as a way to compensate for their respective clisadvantages.
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PMID:The future of 5-HT1A receptor agonists. (Aryl-piperazine derivatives). 135 1

The effects of electric footshock stress(EFS) and conditioned fear stress(CFS) on dopamine(DA) and serotonin(5-HT) metabolism in seven various brain regions of the rat were studied by measuring dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(5-HIAA). EFS for 30 min increased DOPAC and HVA levels in all seven brain regions and increased 5-HIAA levels in the medial prefrontal cortex(mPFC), nucleus accumbens and amygdala. CFS(exposure to an environment paired previously with footshock) increased plasma corticosterone levels and defecation, and induced freezing behavior. It also increased DOPAC levels in the mPFC, paraventricular nucleus of the hypothalamus and lateral hypothalamus, increased HVA levels in the mPFC and amygdala, and increased the 5-HIAA level in the mPFC. In contrast to EFS, which increased DA and 5-HT metabolism in several other brain regions, increased metabolism of both DA and 5-HT was especially marked in the mPFC after CFS. In this model, two classes of anxiolytics were examined for effects on freezing behavior. The benzodiazepine diazepam, a classical anxiolytic, reduced the freezing response. The new anxiolytic ipsapirone, a selective 5-HT1A agonist, also reduced the freezing response. These findings suggest the usefulness of this model for detecting the anxiolytic potential of drugs and examining the relation between 5-HT and anxiety.
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PMID:[From a standpoint of psychiatry: effects of conditioned fear stress on monoaminergic systems in the rat brain]. 135 72

Plasma epinephrine (E), norepinephrine (NE), and corticosterone (CORT) concentrations were determined in the rat before, during, and after a 15-min exposure to a nonelectrified probe on day after receiving electric shock (1.5 mA) through a probe mounted on the wall of the home cage. Rats displayed burying (active coping) if sawdust was provided on the floor and immobility (passive coping) if bedding was absent both during training and testing. The conditioned burying was accompanied by high plasma NE but low E and CORT concentrations, whereas immobility was associated with high CORT and low NE levels. A forced switch from the active to passive coping (training with and testing without sawdust) led to the highest rise in E concentration. The 5-HT1A agonist ipsapirone, with anxiolytic properties, dose-dependently (0.5 and 2.5 mg/kg, IV) reduced defensive burying behavior and increased the amount of time spent on feeding behavior in the presence of bedding material. Both plasma E and CORT levels were further elevated by the higher dose of ipsapirone. In the absence of bedding material, ipsapirone failed to affect immobility behavior, but it dose-dependently elevated the stress-induced increase in E, NE, and CORT concentrations. Accordingly, the behavioral anxiolytic action of the 5-HT1A agonist ipsapirone was restricted to active coping, whereas neuroendocrine activation by the drug was present in all conditions. It is suggested that the effects of ipsapirone on behavioral coping and neuroendocrine regulation are produced by different populations of 5-HT1A receptors in the brain.
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PMID:Neuroendocrine and behavioral responses during conditioned active and passive behavior in the defensive burying/probe avoidance paradigm: effects of ipsapirone. 135 19

Administration of various doses of clonidine increased plasma growth hormone levels. Pretreatment with the alpha 2 adrenergic antagonists, yohimbine and 1-(2-pyrimidyl)piperazine, completely blocked clonidine's effect on growth hormone levels. Pretreatment with the 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL-72222, the 5-HT1A/5-HT2 antagonist, spiperone, and the mixed beta adrenergic/5-HT1B antagonists, l-propranolol and CGP361A, did not attenuate clonidine-induced increases in growth hormone levels. In contrast, pretreatment with the non-selective 5-HT1/2 antagonist, metergoline, and the 5-HT1C/5-HT2-selective antagonist, mesulergine, reduced clonidine-induced increases in growth hormone levels 81 to 87% without affecting clonidine-induced decreases in locomotor activity. Two other 5-HT1C/5-HT2 antagonists, ritanserin and mianserin, also attenuated (47%) clonidine-induced increases in growth hormone levels. Pretreatment with the noradrenergic neurotoxin, DSP4, did not block clonidine's effect on growth hormone levels. Clonidine administration decreased locomotor activity in both the Fawn-Hooded and the Wistar rat strains to the same extent. On the other hand, clonidine administration failed to increase growth hormone levels in the Fawn-Hooded rat strain. These findings suggest that clonidine stimulates growth hormone secretion by activation of alpha 2 adrenergic heteroreceptors present on 5-HT nerve terminals which, in turn, enhance 5-HT activity via stimulation of postsynaptic 5-HT1C receptors to promote growth hormone releasing factor. Furthermore, either 5-HT1C receptors or alpha 2 adrenergic heteroreceptors or both are functionally sub-sensitive in the Fawn-Hooded rat strain relative to the Wistar rat strain.
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PMID:Functional subsensitivity of 5-hydroxytryptamine1C or alpha 2 adrenergic heteroreceptors mediating clonidine-induced growth hormone release in the Fawn-Hooded rat strain relative to the Wistar rat strain. 135 49

The effects of microinfusing L-glutamate, serotonin (5-HT), (+-)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH DPAT; a 5-HT1A agonist), and muscimol (a GABAA agonist) into the dorsal raphe nucleus on the extracellular levels of 5-HT, dopamine (DA) and their metabolites in the nucleus accumbens were studied in unanesthetized, freely moving, adult male Wistar rats, using the technique of microdialysis coupled with small-bore HPLC. Administration of 0.75 micrograms L-glutamate produced a 25-50% increase (P less than 0.05) in the extracellular levels of both 5-HT and DA. On the other hand, infusion of 8-OH DPAT and, to a lesser extent, 5-HT produced a significant (P less than 0.05) decrease in the extracellular levels of both 5-HT and DA. Muscimol (0.25 or 0.50 microgram) had little effect on the extracellular concentrations of 5-HT or DA following its administration. In general, the extracellular levels of the major metabolites of 5-HT and DA in the nucleus accumbens were not altered by microinfusion of any of the agents. The data indicate that (a) the 5-HT neurons projecting to the nucleus accumbens from the dorsal raphe nucleus can be activated by excitatory amino acid receptors and inhibited by stimulation of 5-HT1A autoreceptors, and (b) the dorsal raphe nucleus 5-HT neuronal system may regulate the ventral tegmental area DA projection to the nucleus accumbens.
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PMID:Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat. 135 41


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