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)

Tandospirone (sedil) is a newly developed anxiolytic drug that has a much higher selective affinity for 5-HT1A than dopamine D2 receptors without the binding affinities with noradrenergic, dopaminergic, cholinergic and GABAergic receptors. This agent binds with 5-HT1A receptors located in both 5-HT neurons in the raphe nucleus and other postsynaptic neurons to induce hyperpolarization of the neurons by opening the K+ channels to eventually inhibit the target neuronal activities. With repeated administrations of tandospirone, a decrease in 5-HT2A receptor population was observed. Behavioral studies in experimental animals have demonstrated that tandospirone inhibits conflict in Vogel methods, aggressive behavior and muricide in manners similar to those of diazepam. In addition, tandospirone showed antistress effects in experimental models and antidepressive effects in forced swimming tests. Unlike diazepam, tandospirone does not produce sedative, sleep-inducing, anticonvulsant, nor muscle relaxant effects at doses effective for conflict tests. Drug dependance, one of the serious problems with bezodiazepine, is not observed with repeated treatment of tandospirone in rats and monkeys. Furthermore, tandospirone has been reported to show a significantly more superior or equipotent effect to diazepam in controlling autonomic disturbances, psychiatric cardiovascular and vegetative syndromes as well as neurosis in double blind clinical studies. These effects are probably due to the selective action of tandospirone on 5-HT1A receptors in the limbic system to eventuate anxiolytic and antidepressant effects. A decrease in 5-HT2A receptor population with repeated treatment of tandospirone may have contributed to the antidepressive effect. Furthermore, 5-HT1A receptors relatively, selectively distributed in the limbic system are not involved in sedation, sleep or muscle relaxation. Such unwanted effects of benzodiazepines are thus not observed with tandospirone treatment.
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PMID:[A new approach to innovating selective anxiolytics: pharmacological profile of a novel 5-HT1A agonist (tandospirone)]. 920 24

In silver foxes significant alterations in the activities of basic enzymes of neurotransmitter serotonin metabolism as well as in the densities of receptors caused by selection for the absence of the aggressive defensive reaction to man were demonstrated. In the midbrain and hypothalamus of animals selected for the absence of aggressive behavior, the activity of tryptophan hydroxylase, the key enzyme of serotonin biosynthesis, was found to be remarkably higher than in animals selected for highly aggressive behavior. Domesticated animals were characterized by low activity of the main enzyme of serotonin catabolism, monoamine oxidase type A, increased Michaelis constant km, and an unchanged maximum reaction rate (Vmax). No changes in the specific binding of [3H]-ketanserin and [3H]-8-OH-DPAT in the frontal cortex of domesticated foxes were revealed; however, in the hypothalamus, the low values of Bmax for the [3H]-8-OH-DPAT specific binding were observed, indicating the decreased density of the 5-HT1A receptors. It is assumed that the transformation of a wild aggressive animal into a domesticated one taking place during directional selection is caused by hereditary alterations favored by artificial selection in the activity of the main enzymes of serotonin metabolism and serotonin receptors.
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PMID:[Effect of domestication of the silver fox on the main enzymes of serotonin metabolism and serotonin receptors]. 924 68

Testosterone (T) and its androgenic and estrogenic metabolites modulate the ability of serotonin (5-HT)1A and 5-HT1B agonists to inhibit intermale aggressive behavior. This study tested whether the lateral septum (LS) and medial preoptic area (MPO), which are part of the neuroanatomical substrate for aggression and contain androgen, estrogen, 5-HT1A and 5-HT1B receptors, represent sites where these modulatory effects occur. Gonadectomized CF-1 male mice were given silastic implants containing diethylstilbestrol (DES, a synthetic estrogen) or dihydrotestosterone (DHT, a nonaromatizable androgen) and implanted bilaterally with guide cannula directed at the LS or MPO. They were microinjected with either CGS12066B, a 5-HT1B agonist (400 microM LS, 200 microM MPO); 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A agonist (10 microM LS, 5 microM MPO); or combined CGS + 8-OH-DPAT treatment and tested for aggression 15 min later. When microinjections were given in the LS, androgen-treated males exhibited significantly reduced attack behavior in response to CGS or to CGS + 8-OH-D PAT. The attack behavior of DES-treated males was not reduced by any of the treatments. In contrast, all agonist treatments decreased aggression when injected into the MPO in both hormone conditions. The findings demonstrate regional variation in the ability of androgens and estrogens to modulate 5-HT1A- and 5-HT1B-agonist mediated reductions in aggression.
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PMID:Serotonin agonist-induced decreases in intermale aggression are dependent on brain region and receptor subtype. 930 Jun 2

Recently published studies have suggested that behavioral and neurochemical changes induced by selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors are potentiated by coadministration of a 5-HT1A receptor antagonist. The potentiating effect is hypothesized to be due to antagonism of somatodendritic 5-HT1A autoreceptors. In the present study the effects of concomitant administration of a selective 5-HT reuptake inhibitor with a 5-HT1A receptor antagonist (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide (WAY 100635) or a beta-adrenoceptor and 5-HT1A/1B receptor antagonist (pindolol or (-)-penbutolol) were studied in isolated aggressive mice. WAY 100635 was inactive, but high doses of WAY 100635 produced a marked anti-aggressive effect when combined with a non-effective dose of citalopram or paroxetine. Low doses of pindolol, but not (-)-penbutolol, produced a minor but significant anti-aggressive effect in combination with citalopram or paroxetine. High doses of pindolol or (-)-penbutolol inhibited aggressive behavior, an effect which was reversed by citalopram or paroxetine. The beta-adrenoceptor antagonist, metoprolol, but not the alpha1-adrenoceptor antagonist, prazosin, facilitated the anti aggressive effect of citalopram. The significance of these findings is discussed relative to the above hypothesis.
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PMID:Interaction studies of 5-HT1A receptor antagonists and selective 5-HT reuptake inhibitors in isolated aggressive mice. 936 40

The purpose of the present study was to analyze the role of somatodendritic autoreceptors and postsynaptic 5-HT1A receptors in the modulation of maternal aggressive behavior. The 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) was microinjected (0.2, 0.5 and 2.0 microg/0.2 microl) in different brain areas of female Wistar rats: median raphe nucleus (MnR); medial septal area (MS); anterior corticomedial amygdaloid nucleus (ACoM); and dorsal periaqueductal gray (DPAG). The behaviors of lactating female rats with pups against a conspecific male intruder were recorded on day 7 post-partum. Results showed that in the median raphe nuclei, in the dorsal periaqueductal gray and in the corticomedial amygdaloid nucleus 8-OH-DPAT decreased maternal aggression; while in the medial septum, the intermediate dose (0.5 microg/0.2 microl) of the 5-HT1A receptor agonist increased the aggressive behavior of the lactating female rat. It is concluded that the main role of the 5-HT1A somatodendritic autoreceptors and the post-synaptic receptors of the brain areas studied is to decrease maternal aggression, however, at a specific dosage, 8-OH-DPAT acting on postsynaptic receptors of the medial septal area can increase aggressiveness.
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PMID:8-OH-DPAT in the median raphe, dorsal periaqueductal gray and corticomedial amygdala nucleus decreases, but in the medial septal area it can increase maternal aggressive behavior in rats. 945 82

The effects of acute and repeated administration of antidepressive drugs on apomorphine-induced aggressive behavior and [3H]citalopram binding were studied. In acute behavioral experiments with apomorphine pretreated (1.0 mg/kg, once daily) animals, desipramine (10 mg/kg) and clomipramine (10 mg/kg) enhanced, buspirone (2.5 and 5.0 mg/kg) completely blocked, but fluoxetine, amitriptyline, imipramine (10 mg/kg), and citalopram (10 and 20 mg/kg) had no effect on the intensity of aggressive behavior. Repeated concomitant apomorphine (1.0 mg/kg) and citalopram (10 mg/kg) administration reduced the affinity (Kd) of the 5-HT transporter binding sites in three brain regions. This finding was confirmed by an additional experiment as the effect of citalopram treatment. Repeated apomorphine (1.0 mg/kg) or apomorphine (1.0 mg/kg) plus desipramine (10 mg/kg) treatment had no unidirectional effect on Kd, the maximal number of apparent binding sties (Bmax) was unchanged in all experiments. Our study indicates that the 5-HT reuptake blockade has no major influence on the apomorphine-induced aggressive behavior, but the 5-HT1A receptor subtype may be involved in the mediation of the aggressive behavior in this paradigm.
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PMID:Apomorphine-induced aggressiveness and [3H]citalopram binding after antidepressant treatment in rats. 951 81

Distribution of 5-HT1A receptors was studied in rats genetically predisposed to two basic defense strategies--passive (freezing) or active (aggression) defensive behavior. Specific [3H]8-OH-DPAT binding was assayed in the brain structures of rat strains bred for 40 generations from Wistar stock for predisposition to freezing (catalepsy), and in wild rats bred for low and high aggression to humans. Considerable changes in [3H]8-OH-DPAT binding were found in the brain of rats with hereditary predisposition to catalepsy. A significant decrease in Bmax of specific receptor binding of [3H]8-OH-DPAT in the frontal cortex, and in the striatum as well as an increase in Kd in the hippocampus of cataleptic rats was shown. A clear-cut tendency to decrease of 5-HT1A receptor density was observed in the midbrain and hypothalamus of these rats. A comparison of wild Norway rats bred for aggressiveness against humans with those bred for the absence of affective aggressiveness showed a Bmax decrease without Kd change in the frontal cortex, hypothalamus, and amygdala of aggressive animals. It is hypothesized that 5-HT1A and probably 5-HT1A-like 5-HT7 serotonin receptors are involved in the mechanisms of both active and passive defense reactions, and the high expression of fear-induced defense is associated with their decrease in the frontal cortex. At the same time, the genetically determined preference for a certain defense behavior strategy depends either on the peculiarities of distribution of these receptor types in the brain regions or on some other types of serotonin receptors.
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PMID:Specific [3H]8-OH-DPAT binding in brain regions of rats genetically predisposed to various defense behavior strategies. 958 33

Alterations induced by social isolation (1 day to 18 weeks) in low- and high-active mice (LAM and HAM) were studied in respect to serotonin metabolism, [3H]-8-OH-DPAT binding of presynaptic (midbrain), postsynaptic (hippocampus) 5-HT1A receptors and [3H]-ketanserin binding of cortical 5-HT2A receptors. Individual housing of mice was associated with reduction of serotonin metabolism, depending on isolation time and brain structure. Whereas a transient decrease in the striatum and cortex was detected between 1 week and 6 weeks, reduction of cerebellar and hippocampal serotonin metabolism was found later (12-18 weeks). Serotonergic systems of HAM were found to be more reactive to environmental disturbances, and their serotonin metabolism was more affected by social isolation. Isolation-induced upregulation of cortical 5-HT2A receptors was measured only in HAM. Densities of postsynaptic 5-HT1A receptors in the hippocampus did differ either in grouped or isolated mice. However, there were significant differences in hippocampal 5-HT1A receptor affinity, especially between 1 day and 3 weeks. Transient downregulation of presynaptic 5-HT1A receptors in the midbrain was found in isolated mice between 3 and 6 weeks. These results are discussed in terms of interactions between serotonergic alterations and isolation-induced aggression.
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PMID:Dynamic alterations of serotonergic metabolism and receptors during social isolation of low- and high-active mice. 958 45

The purpose of this investigation was to elucidate the involvement of the serotonergic 5-HT1A system in the control of aggression. The paradigm was the response of a resident mouse to an intruder into its territory. Three experiments were performed to assess the action of various doses of Gepirone (a partial agonist) and (+)WAY 100135 (a putative antagonist), separately and in combination, on aggression and on rectal body temperature. The most consistent action of Gepirone was an increase in the latency to attack. After initiation of fighting, rates of attack, chase, and tail rattling were reduced in a dose-dependent manner by i.p. administration of 2.5, 5, and 10 mg/kg of Gepirone. There was no evidence of sedation or motor impairment, but autogrooming was decreased. When doses of 2.5, 5, and 10 mg/kg of (+)WAY 100135 (WAY) were given, no effects whatsoever on aggressive or other behaviors were observed. In a third experiment, a two-factor design was followed in which injection of WAY (0, 2.5, and 5 mg/kg) was followed 15 min later by injection of Gepirone (0, 2.5, 5, and 10 mg/kg). WAY decreased attack latency, increased attack rate, and attenuated the marked dose-dependent aggression reducing properties of Gepirone. The test procedure resulted in "stress hyperthermia," which was reduced by Gepirone and increased by WAY. In both behavioral and temperature measures, the larger dose of WAY proved to be less effective than the smaller one. The results support the involvement of the 5-HT1A system in the modulation of some forms of aggression.
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PMID:Combined effects of Gepirone and (+)WAY 100135 on territorial aggression in mice. 971 1

One of the critical mechanisms by which alcohol heightens aggression involves forebrain serotonin (5-HT) systems, possibly via actions on 5-HT1A receptors. The present experiments tested the hypothesis that activating 5-HT1A receptors by selective agonists will block the aggression-heightening effects of ethanol. Initially, the selective antagonist WAY 100635 was used to assess whether or not the changes in aggressive behavior after treatment with 8-OH-DPAT and flesinoxan result from action at the 5-HT1A receptors. Resident male CFW mice engaged in aggressive behavior (i.e. attack bites, sideways threats, tail rattle) during 5-min confrontations with a group-housed intruder male. Quantitative analysis of the behavioral repertoire revealed systematic reductions in all salient elements of aggressive behavior after treatment with 8-OH-DPAT (0.1-0.3 mg/kg, i.p.) or flesinoxan (0.1-1.0 mg/kg, i.p.). The 5-HT1A agonists also reduced motor activities such as walking, rearing and grooming, although to a lesser degree. Pretreatment with the antagonist WAY 100635 (0.1 mg/kg, i.p.) shifted the agonist dose-effect curves for behavioral effects to the right. In a further experiment, oral ethanol (1.0 g/kg, p.o.) increased the frequency of attacks in excess of 2 SD from their mean vehicle level of attacks in 19 out of 76 resident mice. Low doses of 8-OH-DPAT (0.03-0.3 mg/kg) and flesinoxan (0.1, 0.3, 0.6 mg/kg), given before the ethanol treatment, attenuated the alcohol-heightened aggression in a dose-dependent fashion. By contrast, these low 5-HT1A agonist doses affected motor activity in ethanol-treated resident mice to a lesser degree, suggesting behavioral specificity of these anti-aggressive effects. The current results support the hypothesized significant role of 5-HT1A receptors in the aggression-heightening effects of alcohol. If these effects are in fact due to action at somatodendritic 5-HT1A autoreceptors, then the anti-aggressive effects would be associated with decreased 5-HT neurotransmission.
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PMID:Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists. 976 54


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