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 effects of the administration of L-triiodothyronine (T3) On the function of 5-HT in the CNS and its influence on the actions of electroconvulsive shock have been examined in mice. A single injection of T3 (100 micrograms/kg) had no effect 24 hr later on either 5-HT1A-mediated hypothermia, induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5 mg/kg) or the 5-HT1B-mediated locomotor response to 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl) 1-H-indole (RU 24969; 50 ng i.c.v.). This treatment increased 5-HT2-induced head-twitches, produced by 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT; 2 mg/kg), but did not alter 5-HT2 receptors in the frontal cortex, suggesting that this potentiation was mediated indirectly through a modulatory neurotransmitter. One injection of T3 had no effect on the concentration of 5-HT in the forebrain or mid/hindbrain, but increased 5-HIAA in the latter region. Daily injections of T3 for 10 days attenuated the responses to both 8-OH-DPAT and RU 24969. Furthermore, 5-MeODMT-induced head-twitches returned to control values and this was accompanied by a 10% decrease in 5-HT2 receptors in the cortex. Repeated administration of T3 increased levels of 5-HT in mid/hindbrain and concentrations of 5-HIAA both here and in forebrain. Hence, treatment with T3 attenuated the function of 5-HT1A and 5-HT1B receptors, but increased 5-HT2-mediated responses, although the time-courses for these effects were different. Triiodothyronine also enhanced the synthesis and turnover of 5-HT in the brain of the mouse. Repeated electroconvulsive shock (90 V, 1 sec) decreased the hypothermia induced by 8-OH-DPAT. However, 5-MeODMT-induced head-twitches were enhanced by acute and repeated electroconvulsive shock. Administration of T3 together with electroconvulsive shock did not alter the effects of electroconvulsive shock on 5-HT1A-mediated hypothermia, but markedly potentiated its actions on 5-HT2-mediated responses. These findings provide possible pharmacological evidence for the suggested antidepressant effects of T3 and the potentiation of antidepressant therapy by this thyroid hormone.
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PMID:The effects of acute and repeated administration of T3 to mice on 5-HT1 and 5-HT2 function in the brain and its influence on the actions of repeated electroconvulsive shock. 297 27

A superfusion system employed to measure the K+-stimulated release of [3H]5-hydroxytryptamine [(3H]5-HT, [3H]serotonin) from a synaptosomal-rich spinal cord tissue preparation was carefully characterized, then used to examine the regulation of spinal 5-HT release. Spinal 5-HT release is apparently modulated by an autoreceptor. Exogenous 5-HT depressed, in a concentration-dependent manner, the K+-stimulated release of [3H]5-HT. Similarly, lysergic acid diethylamide (LSD) produced a concentration-dependent decrease in [3H]5-HT release. Methiothepin and quipazine blocked the inhibition of release induced by exogenous 5-HT. The 5-HT2 receptor antagonists spiperone and ketanserin failed to alter the action of 5-HT at the spinal 5-HT autoreceptor. Spiperone and ketanserin were shown, however, to alter the storage of [3H]5-HT. When used in concentrations greater than 10 nM, the drugs evoked increases in basal [3H]5-HT and [3H]5-hydroxyindoleacetic acid ( [3H]5-HIAA) effluxes which were independent of the presence of calcium ions. A good agreement existed between the potencies of drugs for modifying autoreceptor function and their abilities to compete for high-affinity [3H]5-HT binding in the spinal cord (designated 5-HT1). Furthermore quipazine, in concentrations that preferentially interact with the 5-HT1B subtype, antagonized the actions of exogenous 5-HT on K+-stimulated release. Spiperone, in a concentration that approximated the affinity constant of 5-HT1A sites for the drug, was ineffective in altering the ability of exogenous 5-HT to modulate K+-stimulated [3H]5-HT release. These results suggest that 5-HT1B sites are associated with serotonergic autoreceptor function in the spinal cord.
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PMID:Demonstration of an autoreceptor modulating the release of [3H]5-hydroxytryptamine from a synaptosomal-rich spinal cord tissue preparation. 387 46

Fmtheta is a distinct theta activity in the frontal midline area that appears during performance of mental tasks. It is suggested that relief from anxiety might be reflected in the appearance of Fmtheta. In the present study, the anxiolytic effects of buspirone were investigated using 24 male university students with (Fmtheta group, n = 12) and without (non-Fmtheta group, n = 12) Fmtheta. The subjects were given placebo, buspirone 5 mg and 15 mg in a double-blind, crossover design. Blood samples were obtained, scores were made on the State Trait Anxiety Inventory (STAI), and EEGs were recorded before and during performance of an arithmetic addition. The test was repeated twice: before and 1 h after drug administration. In the Fmtheta group, buspirone dose-dependently produced a decrease in plasma 5-HT and 5-HIAA concentrations and in state anxiety scores and an increase in Fmtheta amounts. In the non-Fmtheta group, however, there were no differences in these items except for 5-HT concentration before and after buspirone administration. These results suggest that anxiety in the Fmtheta group is mainly correlated with 5-HT1A receptor function, and that buspirone may have anxiolytic effects in patients with reactive anxiety but not those with endogenous anxiety.
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PMID:Characteristics of the anxiolytic effects of buspirone in high- and low-anxious normal humans assessed by frontal midline theta activity. 751 2

The present study investigates the role of serotonergic systems in anabolic steroid-induced aggression. An animal model of aggressive dominance was used to assess the chronic effects of testosterone propionate. When rats that had become dominant following administration of testosterone propionate received serotonergic agonists with selectivity for the 5-HT1A receptor (8-OH-DPAT, buspirone, gepirone), the 5-H1B receptor (eltoprazine, TFMPP), or the 5-HT2A/2C receptor (DOM), a dose-dependent decrease in dominance was demonstrated. Pretreatment with three serotonergic antagonists (pizotyline, pirenpirone, and pindolol) blocked agonist-induced reductions in dominance in varying degrees. Nonserotonergic agonists with CNS depressant effects were also tested in dominant animals. The benzodiazepine, chlordiazepoxide, did not reduce dominance except at doses that interfered with motor behavior. The opioid agonist, morphine, dose dependently decreased dominance, but this effect was reversible with administration of the serotonergic antagonist, pirenpirone, suggesting the antidominant effect of morphine had a serotonergic component. Biochemical experiments demonstrated that following chronic testosterone propionate, there was a decrease in levels of 5-HT and 5-HIAA in the hippocampus but not in the striatum or the frontal cortex. Chronic testosterone propionate also caused an increase in the affinity of [3H]8-OH-DPAT for the 5-HT1A receptor but no corresponding change in the density of 5-HT1A binding sites in the hippocampus. There was also no change in the properties of the 5-HT2 receptor in the frontal cortex following chronic testosterone propionate. These data suggest that serotonergic systems may play an important role in the control of anabolic steroid-induced aggressive dominance.
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PMID:Serotonergic control of androgen-induced dominance. 752 25

The activity of tianeptine (2.5 and 5.0 mg/kg twice daily, i.p.) and of sertraline (5.0 mg/kg, twice daily, i.p.) were assessed in three animal models of depression. In the Behavioural Despair Test, acute treatment with sertraline or tianeptine (5.0 mg/kg) significantly reduced the immobility time. In the olfactory bulbectomized (OB) rat model, chronic treatment with tianeptine (2.5 and 5.0 mg/kg) or sertraline (5.0 mg/kg) antagonized the lesion-induced hyperactivity in the "open field" apparatus. The hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.15 mg/kg, s.c.) was significantly attenuated after chronic setraline treatment, whereas tianeptine was inactive at the 2 doses tested. Neither drug affected the hypersection of corticosterone that occurs at the light:dark interface. A reduction in the serotonin metabolite 5-HIAA was found in the hypothalamus of sertraline-treated sham rats. It can be concluded that although the neurochemical properties of sertraline and tianeptine differ, they demonstrate similar antidepressant-like activities in the Behavioural Despair and OB rat models. The lack of effect of tianeptine on the 8-OH-DPAT-induced hypothermic effect indicates that it does not induce 5-HT1A subsensitivity, contrary to most antidepressants.
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PMID:The effect of tianeptine and sertraline in three animal models of depression. 753

Administration of various doses of DOI (a 5-HT2A/5-HT2C agonist) produced hyperthermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Similarly, administration of various doses of ipsapirone (a 5-HT1A agonist) produced hypothermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Furthermore, m-CPP (a 5-HT agonist)-induced increases in growth hormone levels were also significantly less in the FH rat strain relative to the Wistar rat strain. There was no significant difference in the levels of either 5-HT or 5-HIAA between the two rat strains in the frontal cortex, hippocampus, hypothalamus, and striatum. In the brain stem, however, both 5-HT and 5-HIAA levels were significantly lower in the FH rat strain relative to the Wistar rat strain. On the other hand, 5-HT turnover rate was significantly higher in the hypothalamus and striatum and significantly lower in the hippocampus in the FH rat strain relative to the Wistar rat strain. These findings provide further evidence for altered serotonergic function in the FH rat strain and, in addition, suggest that the FH rat strain may prove to be a useful genetic model for some neuropsychiatric disorders with possible abnormalities in serotonergic function such as depression, obsessive-compulsive disorder, and the eating disorders.
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PMID:Functional and biochemical evidence for altered serotonergic function in the fawn-hooded rat strain. 753 10

Intrastriatal administration of ipsapirone (IPSA, 0.5 and 1 mM), an agonist of 5-HT1A serotonergic receptors, enhanced in a dose-dependent manner DA release in the rat striatum, without affecting levels of the DA metabolites DOPAC and HVA. The IPSA evoked-enhancement of DA release was followed by a decrease in 5-HIAA concentration. The effects of intrastriatal administration of IPSA were mimicked by 8-OH-DPAT (0.5 mM), another agonist of 5-HT1A receptors, and were antagonized by the peripheral administration of metergoline (5 mg/kg ip) and intrastriatal administration of NAN-190 (0.5 mM). IPSA given peripherally (10 mg/kg ip) also enhanced DA release; that effect was accompanied by an increase in DOPAC and HVA levels. It is postulated that IPSA increases the release of DA from nigrostriatal terminals via activation of striatal 5-HT1A receptors in a manner independent of the activation of 5-HT1A receptors in the dorsal raphe nuclei.
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PMID:Enhancement by ipsapirone of dopamine release in the rat striatum. 769 36

In mixed-sex rat groups consistent asymmetries in offensive and defensive behaviors of male dyads are associated with the development of dominance hierarchies. Subordinate males can be differentiated from dominants on the basis of both agonistic and non-agonistic behaviors, wound patterns, weight changes. Their behavior changes suggest chronic defensiveness and are also broadly isomorphic to many of the symptoms of depression; their voluntary alcohol consumption increases, and their life-spans are shortened. Both subordinate and dominant males tend to show organ change compared to non-grouped controls, with adrenal and spleen enlargement and thymus reduction. However, these changes appear to be more marked in subordinates, and only subordinates show reduced testes weights. Basal corticosterone (CORT) levels were sharply higher, and plasma testosterone (T) sharply lower, in subordinates compared to both dominants and controls, and reduced corticosterone binding globulin further enhanced free CORT for subordinates particularly. Many subordinates failed to show a normal CORT response to restraint stress. Subordinates also appear to show widespread changes in serotonin systems, with increased 5-HIAA/5-HT ratios in a number of brain areas, and alterations of 5-HT1A receptor binding at some sites. These changes suggest that subordination, a common and consistent feature of life for many animals living in social groups, may be a particularly relevant model for investigating the behavioral, neural and endocrine correlates of chronic stress.
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PMID:Subordination stress: behavioral, brain, and neuroendocrine correlates. 813 39

SR 57746A (1-[2-(naphth-2-yl) ethyl]-4-(3-trifluoromethylphenyl)-1, 2, 5, 6 tetra-hydropyridine hydrochloride) binds competitively, and with high affinity (Ki = 2.0 +/- 0.7 nM) to 5-HT1A receptors from rat hippocampus in vitro, but has much less affinity for other 5-HT receptor subtypes (IC50 > 650 nM). SR 57746A produces a concentration-dependent inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal homogenates, with a maximal effect identical to that of 8-OH-DPAT, suggesting that SR 57746A behaves as a full agonist in this experimental model. SR 57746A potently displaces [3H]8-OH-DPAT binding to rat hippocampal membranes ex vivo, with an ID50 of 11.1 mg/kg po, 30 min after administration, and 2.8 mg/kg po, 2 h after administration. This effect of SR 57746A is long-lasting (at least 24 hours at 10 mg/kg po). SR 57746A does not modify the levels of 5-HT or DA in various brain areas, but decreases the concentrations of 5-HIAA, and increases those of DOPAC, HVA and 3-MT. Following i.v. administration, SR 57746A (0.095 to 0.25 mg/kg) inhibits the spontaneous firing of dorsal raphe neurones, but does not modify the activity of DA neurones in the substantia nigra or ventral tegmental area. Thus, SR 57746A is a potent, selective and full agonist at 5-HT1A receptors in vitro and vivo.
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PMID:Biochemical and electrophysiological properties of SR 57746A, a new, potent 5-HT1A receptor agonist. 831 96

The effects of partial 5-HT1A receptor agonists buspirone (0.010-4.0 mg/kg), ipsapirone (0.010-6.0 mg/kg), and gepirone (0.025-4.0 mg/kg) on sleep and waking were studied in vehicle-treated and 5,7-dihydroxytryptamine (5,7-DHT)-injected rats. 5,7-DHT-treated animals showed a marked and significant serotonin and 5-HIAA depletion in the raphe regions of the pons and upper brain stem, cerebral cortex, hippocampus, and striatum. Subcutaneous administration of the partial agonists to both the vehicle-infused and the 5,7-DHT-treated animals significantly increased waking (W) and reduced light sleep (LS), slow-wave sleep (SWS), and REM sleep (REMS). Pretreatment with (-)pindolol (2.0 mg/kg) reversed the effects of buspirone and gepirone on W and non-REM sleep (LS + SWS) whereas REMS remained suppressed. (-)-Pindolol failed to reverse the effects of ipsapirone on sleep and W. The present results tend to indicate that increased W after acute administration of buspirone, ipsapirone, or gepirone depends upon the activation of postsynaptic 5-HT1A receptors. The well-known anxiolytic action observed after chronic administration of the azapirones seems to be related to mechanisms other that these involved in their stimulant effect.
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PMID:Sleep and waking in 5,7-DHT-lesioned or (-)-pindolol-pretreated rats after administration of buspirone, ipsapirone, or gepirone. 857 95


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