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 present electrophysiological experiments were undertaken to investigate the effect of desipramine and d-amphetamine on noradrenergic neurotransmission in the rat central nervous system. The effectiveness of electrical stimulation of the locus coeruleus and of microiontophoretic application of norepinephrine (NE) in suppressing the firing activity of CA3 pyramidal neurons was studied in the dorsal hippocampus. Desipramine (0.5 and 5 mg/kg i.v.) and d-amphetamine (0.25 and 5 mg/kg i.v.) decreased the effectiveness of locus coeruleus stimulation and prolonged the effect of microiontophoretically applied NE on the same pyramidal neurons. Subsequent i.v. administration of idazoxan, an alpha 2-adrenoceptor antagonist, reversed the effects of desipramine and d-amphetamine on the effectiveness of locus coeruleus stimulation and decreased that of microiontophoretically applied NE. In addition, idazoxan prevented the effect of subsequent administration of desipramine (5 mg/kg i.v.) on the effectiveness of locus coeruleus stimulation. High doses of d-amphetamine (5 and 10 mg/kg i.v.) decreased the firing activity of hippocampus pyramidal neurons by 70 and 98%, respectively, whereas low doses of desipramine (0.5 mg/kg i.v.) or of d-amphetamine (0.25 mg/kg i.v.) were without effect. After lesioning of NE projections with 6-hydroxydopamine, the effect of the 5 mg/kg dose of d-amphetamine on the firing activity of hippocampus pyramidal neurons was markedly reduced, whereas the cumulative 10 mg/kg dose of d-amphetamine completely suppressed, as in control rats, the firing activity of these neurons. This effect of d-amphetamine in 6-hydroxydopamine-pretreated rats was reversed by the administration of the 5-HT1A receptor antagonist BMY 7378. These data provide evidence that acute administration of desipramine and d-amphetamine decreases the effectiveness of locus coeruleus stimulation by increasing the activation of terminal alpha 2-adrenoceptor autoreceptors. In addition, acute administration of high doses of d-amphetamine decreases the firing rate of hippocampus pyramidal neurons by increasing NE and serotonin release.
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PMID:Effect of desipramine and amphetamine on noradrenergic neurotransmission: electrophysiological studies in the rat brain. 133 78

5-hydroxytryptamine (5-HT) hyperpolarizes hippocampal pyramidal cells in both areas CA1 and CA3 through an increase in potassium conductance. The receptor mediating the hyperpolarization in CA1 has been characterized as the 5-HT1A receptor, but has not been identified in area CA3. Intracellular recording techniques were used to record from CA1 and CA3 pyramidal cells in a hippocampal slice preparation. 5-HT agonists and antagonists were applied in known concentrations by bath perfusion. Antagonists were tested alone and for their ability to block the hyperpolarization elicited by 5-HT. The 5-HT1 agonist 5-carboxyamidotryptamine and 5-HT were full agonists and the 5-HT1A-selective ligand 8-hydroxydipropyl-aminotetralin hydrobromide was a partial agonist in both CA3 and CA1. The rank order potency was 5-carboxyamidotryptamine > 8-hydroxydipropyl-aminotetralin hydrobromide > 5-HT for both regions. The agonists were a half-log unit less potent and the maximum response elicited by 5-carboxyamidotryptamine and 5-HT was greater in area CA3 than in area CA1. The selective 5-HT1A antagonist BMY 7378 and the 5-HT1A/2 antagonist spiperone were competitive in area CA1, but insurmountable in area CA3. Other 5-HT antagonists that were not effective in blocking the 5-HT-mediated hyperpolarization included ketanserin, odansetron and BRL 24924. Based on these results, we conclude that the hyperpolarization elicited by 5-HT in areas CA1 and CA3 is mediated by the 5-HT1A receptor. However, there are significant differences in the nature of the 5-HT1A receptor-mediated hyperpolarization that may be attributed to differences in receptor-effector number, receptor-effector coupling and/or the structure of the recognition site.
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PMID:Comparison of 5-hydroxytryptamine1A-mediated hyperpolarization in CA1 and CA3 hippocampal pyramidal cells. 140 96

Quantitative autoradiography was used to evaluate the effects of adrenalectomy (ADX) and corticosterone (CORT) on binding at 5-HT1A and 5-HT1B receptors in the dorsal hippocampus and cortex of the rat. ADX increased binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin at 5-HT1A receptors in the oriens and lacunosum moleculare layers of CA2 and CA3, in the lacunosum moleculare layer of CA4 region, and in the dentate gyrus. In restraint-stressed ADX rats, binding was increased only in the oriens and lacunosum moleculare layers of CA2. Restoration of baseline levels of CORT reversed the effects of ADX on 5-HT1A receptors in the hippocampus, while high levels of CORT decreased binding at 5-HT1A receptors in the dentate gyrus. No treatment affected binding at 5-HT1A receptors in the CA1 region of the hippocampus or in the cortex. ADX increased binding of [125I]iodocyanopindolol at 5-HT1B receptors in the infrapyramidal dentate, but this effect was not observed in ADX rats that were restrained. CORT treatment in both ADX and SHAM (adrenally intact) rats resulted in binding at 5-HT1B receptors that was lower than that in untreated ADX and SHAM rats in the infrapyramidal dentate, and lower than that in ADX rats in the suprapyramidal dentate and CA4. In ADX and SHAM rats, CORT also reduced binding at 5-HT1B receptors in area 2 of the cortex. It is suggested that decreases in binding at 5-HT1A and 5-HT1B/1D receptors resulting from chronic exposure to high levels of CORT may also occur in animals that fail to adapt to chronic severe stress. Such changes in binding may play important roles in the etiology of depression.
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PMID:Autoradiographic analyses of the effects of adrenalectomy and corticosterone on 5-HT1A and 5-HT1B receptors in the dorsal hippocampus and cortex of the rat. 153 16

The acute and long-term effects of the antidepressant/anxiolytic selective 5-HT1A receptor ligand, tandospirone (SM-3997) on 5-HT neurotransmission were assessed using single-cell extracellular recording in chloral hydrate-anaesthetized rats. The acute intravenous administration of tandospirone decreased the firing rate of 5-HT neurones of the dorsal raphe (ED50 = 9.1 +/- 1.1 micrograms/kg). A treatment with tandospirone for 2 days (10 mg/kg/day, s.c.), markedly reduced the firing activity of 5-HT neurones of the dorsal raphe; this was followed by a partial recovery after 7 days and by complete recovery after 14 days of administration of tandospirone. After treatment with tandospirone for 14 days (10 mg/kg/day, s.c.), the responsiveness of 5-HT neurones to the intravenous administration of LSD was reduced, suggesting that somatodendritic 5-HT autoreceptors had desensitized. The depressant effects of microiontophoretically-applied tandospirone and 5-HT, on the firing activity of CA3 pyramidal neurones in the hippocampus were blocked by the intravenous injection of the 5-HT1A receptor antagonist, BMY-7378. The depressant effect of microiontophoretically-applied 5-HT onto these same neurones was markedly reduced during concurrent background application of tandospirone, suggesting that the latter acted as a partial agonist at postsynaptic 5-HT1A receptors. The sustained administration of tandospirone for 14 days (10 mg/kg/day, s.c.) altered neither the effectiveness of microiontophoretically-applied 5-HT and tandospirone nor that of endogenous 5-HT, released by the electrical simulation of the afferent 5-HT pathway, in suppressing the firing activity of pyramidal neurones in the hippocampus, suggesting that postsynaptic 5-HT1A receptors had not desensitized. Furthermore, long-term treatment with tandospirone did not alter the sensitivity of the terminal 5-HT autoreceptor. It is thus concluded that desensitization of somatodendritic 5-HT autoreceptors permits 5-HT neurones to regain their physiological rate of firing during long-term treatment with tandospirone and, consequently, to release a normal amount of 5-HT into the synaptic cleft. This, combined with the sustained activation of normosensitive postsynaptic 5-HT1A receptors by tandospirone, during such a treatment, should result in an enhanced tonic activation of postsynaptic 5-HT1A receptors.
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PMID:Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--I. Effects of acute and long-term administration of tandospirone on serotonin neurotransmission. 168 46

1-(2-Pyrimidinyl)-piperazine (1-PP) is a common metabolite of the antidepressant/anxiolytic 5-HT1A agonists, tandospirone (SM-3997), gepirone, buspirone and ipsapirone. The present electrophysiological studies were undertaken to characterize in vivo the effect of 1-PP on noradrenergic (NE) neurotransmission in rat brain. At small doses, 1-PP (ED50 = 80 micrograms/kg, i.v.) reversed the depressant effect of the alpha 2-adrenoceptor agonist, clonidine (20 micrograms/kg, i.v.) on the firing activity of NE neurones of the locus coeruleus. After long-term treatment with tandospirone (10 mg/kg/day, s.c. x 14 days), the responsiveness of these NE neurones to intravenous administration of clonidine was decreased but their mean firing frequency remained within the control range. The effect of 1-PP on the postsynaptic alpha 2-adrenoceptor of pyramidal neurones in the hippocampus was investigated: intravenous administration of 1-PP (2-8 mg/kg, i.v.) reduced the effect of microiontophoretically-applied NE on CA3 pyramidal neurones of the dorsal hippocampus, without affecting their responsiveness to GABA and 5-HT. The effect of the electrical stimulation of NE neurones of the locus coeruleus in reducing firing activity of pyramidal neurones, which is mediated by postsynaptic alpha 1-adrenoceptors, was increased by 47% after acute administration of 1-PP (4 mg/kg, i.v.), presumably as a result of blockade of terminal alpha 2-autoreceptors. The effectiveness of these stimulations remained unchanged after long-term treatment with tandospirone. Furthermore, the decrease in the effectiveness of stimulation of the locus coeruleus, obtained by increasing the frequency from 1 to 5 Hz, a phenomenon due to an increased activation of terminal alpha 2-adrenergic autoreceptors by endogenous NE, remained unaltered after long-term treatment with tandospirone. In addition to the initial depressant effect, stimulation of the locus coeruleus induces a late activation of these neurones which is mediated by a beta-adrenoceptor. The degree of activation induced by stimulation of the locus coeruleus was similar in controls and in long-term tandospirone-treated rats. It is concluded that 1-PP acts as an antagonist at somatodendritic and terminal alpha 2-adrenergic autoreceptors, as well as at postsynaptic alpha 2-adrenoceptors, in the central nervous system of the rat. However, the levels of 1-PP attained after long-term administration of tandospirone were not sufficient to modify NE neurotransmission.
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PMID:Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--II. Effects of acute administration of 1-PP and long-term administration of tandospirone on noradrenergic neurotransmission. 168 47

The present study examined the comparative distribution of 5-HT1A receptor mRNA and 5-HT1A receptors in rat brain using a combination of in situ hybridisation histochemistry and in vitro receptor autoradiography. 5-HT1A mRNA was visualized using a 910 bp cRNA probe synthesised from a BalI-PvuII fragment of the rat 5-HT1A reetor gene, while 5-HT1A receptors were labelled with the 5-HT1A-selective ligand 8-OH-DPAT. In general terms, there was a complementary distribution of cells expressing 5-HT1A receptor mRNA and 5-HT1A receptor sites. High levels of both 5-HT1A mRNA and 5-HT1A receptors were evident in the hippocampal formation (CA1, CA3, dentate gyrus), entorhinal cortex, and raphe nuclei and lower levels in neocortex and thalamus. Although 5-HT1A mRNA was not expressed in any regions which did not also exhibit 5-HT1A receptors, within both the diagonal band and the medial septal nucleus mRNA levels were proportionately higher than 5-HT1A receptor levels, possibly reflecting receptor transport or a heterogeneity in 5-HT1A receptor turnover mechanisms. 5-HT1A receptor mRNA and 5-HT1A binding sites were undetectable in caudate/putamen and cerebellar regions. The present data indicate the synthesis of 5-HT1A receptors both in raphe serotonergic cells and anatomically specific serotonergic projection areas, further supporting both a presynaptic autoregulatory and postsynaptic modulatory role for this receptor in serotonergic transmission.
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PMID:Comparative anatomical distribution of 5-HT1A receptor mRNA and 5-HT1A binding in rat brain--a combined in situ hybridisation/in vitro receptor autoradiographic study. 179 49

The neurobiologic mechanisms whereby the long-term administration of different antidepressant treatments enhance the efficacy of 5-HT synaptic transmission was investigated using an electrophysiologic paradigm in chloral hydrate anesthetized rats. Repeated electroconvulsive shocks (ECS; administered every other day for 14 days) as well as the sustained 21-day administration of the tricyclic antidepressant imipramine (10 mg/kg/day) and of the selective 5-hydroxytryptamine (5-HT) reuptake blocker paroxetine (5 mg/kg/day), increased the suppressant effect of the electrical stimulation of the afferent 5-HT pathway on the firing activity of CA3 hippocampus pyramidal neurons. The long-term treatments with imipramine and ECS, but not with paroxetine, increased the responsiveness of postsynaptic CA3 hippocampus pyramidal neurons to the microiontophoretic application of 5-HT and to that of the selective 5-HT1A receptor ligand 8-OH-DPAT. In contrast, the long-term treatment with paroxetine, but not with imipramine or ECS, attenuated the negative feedback exerted by terminal 5-HT autoreceptors on 5-HT release. This was indicated by two series of experiments. First, the capacity of the acute intravenous injection of the terminal 5-HT autoreceptor antagonist methiothepin to increase the efficacy of the stimulation was abolished in paroxetine-treated rats. Second, the decreased suppressant effect on pyramidal neuron firing activity usually obtained by increasing the frequency of the stimulation from 1 to 5 Hz (shown to be due to an increase in terminal 5-HT autoreceptor activation at the higher frequency) was also reduced in paroxetine-treated rats. The present data confirm and extend those of previous electrophysiologic studies showing that an enhanced 5-HT synaptic transmission is a common end result of long-term administration of various types of antidepressant treatments. Furthermore, they suggest that the mechanisms underlying this enhanced synaptic transmission differ according to the type of treatment administered. Tricyclic antidepressants and ECS enhance 5-HT synaptic transmission by increasing the sensitivity of postsynaptic 5-HT1A receptors, whereas selective 5-HT reuptake blockers produce this effect by reducing the function of terminal 5-HT autoreceptors, thereby increasing the amount of 5-HT released per stimulation-triggered action potential.
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PMID:Presynaptic and postsynaptic modifications of the serotonin system by long-term administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. 2654 64

There have been few studies investigating the effect of treatments that alter serotonergic neurotransmission on the density of serotonin1A (5-hydroxytryptamine1A [5-HT1A]) receptors, even though lesioning serotonergic neurons has been reported to enhance certain responses thought to be due to activation of 5-HT1A receptors and repeated treatment of rats with different types of antidepressants can diminish 5-HT1A-mediated responses. Consequently, the binding of 3H-8-hydroxy-2-(di-n-propylamino)-tetralin (DPAT) to 5-HT1A receptors in serotonergic cell body and terminal field areas of rat brain was measured by quantitative autoradiography following either the lesioning of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT), or after chronic administration of monoamine oxidase inhibitors (MAOIs) (clorgyline, phenelzine, or tranylcypromine) or inhibitors of 5-HT uptake (citalopram or sertraline). Treatment of rats with 5,7-DHT did not cause any significant increase in binding of 3H-DPAT to 5-HT1A receptors in any area of the brain examined. There was no significant reduction in the binding of 3H-DPAT in terminal field areas of serotonergic innervation in rats treated with 5,7-DHT except in the CA2/CA3 region of the hippocampus (33% to 35% reduction). In the dorsal and median raphe nuclei, the specific binding of 3H-DPAT was reduced by treatment of rats with 5,7-DHT. In lesioned rats, the binding of 3H-cyanoimipramine (3H-CN-IMI) to uptake sites for serotonin was essentially eliminated in all terminal field areas examined, as well as in the dorsal and median raphe nuclei. Repeated administration of clorgyline, phenelzine, tranylcypromine, citalopram, or sertraline produced an attenuation of the hypothermic response of rats to acute subcutaneous injection of the 5-HT1A-receptor-agonist DPAT. In spite of this change in 5-HT1A responsivity, these treatments caused in the same animals no consistent change in the binding of 3H-DPAT in either serotonergic cell body or terminal field areas. Of the five drugs studied that diminished DPAT-induced hypothermia, only phenelzine and clorgyline significantly reduced the binding of 3H-DPAT, and even then in only a few of the 12 areas of brain measured. As a result of treatment of rats with tranylcypromine there was a significant increase in the binding of 3H-DPAT in the CA2/CA3 region of the hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A quantitative autoradiographic study of serotonin1A receptor regulation. Effect of 5,7-dihydroxytryptamine and antidepressant treatments. 202 79

In the present electrophysiological studies the effects of the activation of putative presynaptic benzodiazepine receptors (BZR) in modulating serotonergic (5-HT) transmission in dorsal hippocampus were investigated in chloral hydrate-anesthetized rats. The effectiveness of the electrical stimulation of the ascending 5-HT pathway on the firing activity of CA3 hippocampus pyramidal neurons was modulated by the intravenous administration of BZR ligands. The BZR agonists, diazepam, lorazepam and CL 218,872, dose-dependently enhanced the effectiveness of the stimulation. In contrast, the BZR inverse agonist, FG 7142, dose-dependently decreased it. The effects of agonist and inverse agonist BZR ligands were blocked by the specific BZR antagonist flumazenil. Diazepam and FG 7142 did not modify the efficacy of microiontophoretic applications of gamma-aminobutyric acid and 5-HT onto hippocampal CA3 neurons. BMY 7378, a 5-HT1A receptor antagonist which blocks the effect of the endogenous 5-HT released by the electrical stimulation of 5-HT fibers in this paradigm, also blocked the enhancing action of diazepam on the effectiveness of the stimulation. These results indicate that the activation of BZR of type I modulates 5-HT neurotransmission, presumably through a presynaptic regulatory mechanism.
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PMID:Benzodiazepine receptors modulate 5-hydroxytryptamine neurotransmission in the rat hippocampus: in vivo electrophysiological evidence. 216 98

Chronic injection of iminodipropionitrile (IDPN) to rats causes persistent motor abnormalities such as hyperactivity, lateral and vertical dyskinesia of the neck, and random circling. These behavioral changes are very similar to those observed after the acute administration of serotonin (5-HT) agonists in rodents. Moreover, some aspects of this syndrome are reproduced by stimulation of 5-HT1A receptors. The present quantitative autoradiographic study revealed a number of changes in 8-hydroxy-2-[di-n-propylamino-3H]tetralin (8-OH[3H]DPAT)-labeled 5-HT1A receptors in the brains of IDPN-treated rats. There were significant increases of 8-OH[3H]DPAT binding in the frontal cortex and in the caudate-putamen. In contrast, there were significant decreases in the interpeduncular nucleus, the pyramidal layer of the CA3 field of hippocampus, the superior colliculus and the pars reticulata of the substantia nigra. These results provide further evidence for the involvement of the 5-HT system in the development of the IDPN-induced dyskinetic syndrome.
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PMID:Regional changes in brain 5-HT1A serotonin receptors in the rat model of persistent spasmodic dyskinesias induced by iminodipropionitrile. 253 54


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