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)

1. We devised a new light/dark transition apparatus, recorded transitions, % time animals spent outside the dark chambers (% time) and locomotor activity, and evaluated this apparatus by testing anxiolytics, non-anxiolytic drugs and putative anxiogenic drugs in mice. 2. Diazepam and alprazolam significantly increased transitions, % time and locomotor activity. The effects of 1 mg/kg (i.p.) diazepam on these parameters in this modified test were blocked by flumazenil, a selective benzodiazepine antagonist. 3. Anxiogenic drugs such as beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and picrotoxin significantly decreased all three parameters. Another anxiogenic drug, yohimbine, also significantly decreased transitions and locomotor activity, but it significantly increased % time at 5 mg/kg (i.p.). 4. Imipramine (5-10 mg/kg, i.p.), an antidepressant, sulpiride (10-25 mg/kg, i.p.), an antipsychotic drug, and scopolamine (0.1-1 mg/kg, i.p.), an anticholinergic drug, had no effect. 5. Buspirone, a partial 5-HT1A receptor agonist, produced parameter changes similar to those induced by anxiolytic benzodiazepines. 8-OH-DPAT, a full 5-HT1A receptor agonist, significantly increased transitions and locomotor activity but not % time. 5-HT3 receptor antagonists, ICS205-930 and MDL72222, did not have any effect on these parameters. 6. Methamphetamine (1-2 mg/kg, i.p.) increased all parameters, while caffeine increased only locomotor activity. 7. The present findings indicate that the modified light/dark transition test is very simple and easy to perform for testing the anxiolytic and anxiogenic effects of drugs.
Gen Pharmacol 1995 Jan
PMID:The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs. 771 61

(S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin, 0.5-4.0 mg/kg i.v.] did not significantly alter the firing rate of 5-hydroxytryptamine (5-HT) containing neurons in the dorsal raphe nucleus (DRN) as a group, although some individual cells were activated whereas others were depressed. However, (S)-UH-301 (2.0 mg/kg i.v.) consistently reversed the inhibition of DRN-5-HT cells produced by the selective 5-HT1A receptor agonist (R)-8-OH-DPAT (0.5 microgram/kg i.v.) and the dose-response curve for this effect of (R)-8-OH-DPAT was markedly shifted to the right by pretreatment with (S)-UH-301 (1.0 mg/kg i.v.). These results support the notion that (S)-UH-301 acts as an antagonist at central 5-HT1A receptors.
J Neural Transm Gen Sect 1994
PMID:The 5-HT1A receptor antagonist (S)-UH-301 blocks the qR)-8-OH-DPAT-induced inhibition of serotonergic dorsal raphe cell firing in the rat. 782 69

In this study, we examined the response of spontaneously active as well as quiescent cells (L-glutamate-activated) in the rat medial prefrontal cortex (mPFc) to the iontophoresis of 2-methylserotonin (2-Me-5-HT, 5-HT3 receptor agonist), (+/-)-2,5-dimethoxy-(4-iodo-phenyl)-2-aminopropane (DOI, 5-HT2A,2C receptor agonist), 8-hydroxy-N,N-di-propylamino tetralin (8-OH-DPAT, 5-HT1A receptor agonist) and gamma-aminobutyric acid (GABA, a non-selective GABA receptor agonist) after the intracerebral administration of pertussis toxin, an inactivator of the Gi/o protein. This was accomplished using the techniques of extracellular single cell recording and iontophoresis. The administration of pertussis toxin (0.5 microgram, 24 hours before the experiment) into the mPFc did not alter the response of mPFc cells to the iontophoresis of DOI, 2-Me-5HT or GABA compared to saline treated controls. However, the response of mPFc cells to the iontophoresis of 8-OH-DPAT was significantly attenuated in the animals pretreated with pertussis toxin compared to controls. These results suggest that the 5-HT1A but not 5-HT2A,2C or 5-HT3 receptor is coupled to the Gi/o protein.
J Neural Transm Gen Sect 1994
PMID:Effect of pertussis toxin on the response of rat medial prefrontal cortex cells to the iontophoresis of serotonin receptor agonists. 786 72

1. The effects of buspirone, gepirone, ipsapirone and tandospirone on spontaneously discharging serotonergic neurons of the dorsal raphe were determined under the same experimental conditions. 2. Buspirone, gepirone, ipsapirone and tandospirone were equally efficacious and acted in a dose-dependent manner to totally inhibit the spontaneous activity of serotonergic neurons. 3. Based on their effects six min after administration (i.p.), their ED50 values were: buspirone, 134 micrograms/kg; ipsapirone, 220 micrograms/kg; gepirone, 225 micrograms/kg; tandospirone, 198 micrograms/kg. 4. The similarity of these ED50 data suggest that they share a similar chemical structure that binds to the 5-HT1A receptor, most likely it is "N-C-C-C-C-N" aliphatic backbone. 5. Buspirone and tandospirone required 4 or more min to totally block the spontaneous activity, while gepirone and ipsapirone blocked it in 3 min. 6. The dose-response curves from buspirone and tandospirone demonstrated enough dissimilarity to the dose-response curves from gepirone and ipsapirone to suggest differences in their rates of absorption, and/or differences in the production of active and inactive metabolites.
Gen Pharmacol 1994 Jul
PMID:The effects of azapirones on serotonin1A neurons of the dorsal raphe. 795 28

Microinjections of the neuroexcitotoxin, domoic acid (DOM), in the ipsilateral rat hippocampal CA-3 region, induced generalized electrical seizure discharge activity, characterized by spikes and waves, followed by intermittent burst discharges. Computerized EEG analysis exhibited relative dominance of delta and theta and reductions in alpha and beta activities during domoic acid epileptogenesis. Seizure discharge activity was attenuated by the microinjection of the 5-HT1A agonist, 8-hydroxy-2-(di-N-propylamino)tetralin(8-(OH)-DPAT) and augmented by the specific 5-HT1A antagonist, spiroxatrine in the contralateral hippocampal CA-3 region. Neuronal recovery following 8-(OH)-DPAT was associated with significant reductions in the relative dominance of delta and theta and increases in the alpha and beta activities. The results suggest that activation of serotonergic 5-HT1A receptor in the hippocampus has a neuroprotective action.
J Neural Transm Gen Sect 1993
PMID:Suppression of domoic acid induced seizures by 8-(OH)-DPAT. 821 55

The binding affinity of a possible antidepressant drug, dihydroergosine, for various 5-HT1 receptor subtypes was studied in the hippocampal rat brain membranes. Dihydroergosine displaced the binding of [3H]5-HT to the whole population of hippocampal 5-HT1 receptors with high affinity (Ki = 4.8 nM). The displacement curve was shallow and the slope factor less than unity, suggesting the interaction of dihydroergosine with multiple binding sites. When 8-OH-DPAT (100 nM) + chlorpromazine (500 nM), CGS 12066 B (200 nM) + ritanserin (500 nM), and (+/-)pindolol (1 microM) were included to block 5-HT1A + 5-HT1C, 5-HT1B + 5-HT1C, and 5-HT1A + 5-HT1B receptor subtype respectively, the competition studies have shown that under these selective conditions dihydroergosine binds with the highest affinity for 5-HT1B (Ki = 0.48 nM), with 8.7 times lower affinity for 5-HT1A (Ki = 4.2 nM) and with a moderate affinity for 5-HT1C (Ki = 156 nM) receptor subtype. While our previous studies suggested that dihydroergosine stimulates 5-HT1A and inhibits 5-HT2 receptors, this study suggests that the high affinity of this drug for 5-HT1B receptors should not be neglected.
J Neural Transm Gen Sect 1993
PMID:Possible antidepressant dihydroergosine preferentially binds to 5-HT1B receptor sites in the rat hippocampus. 832 68

1. We studied the effects of tandospirone, a novel serotonin (5-HT)1A receptor-related anxiolytic, on the intracellular second messenger systems and neurotransmitter release. 2. Tandospirone inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT1A receptors and had high efficacy comparable to 5-HT1A receptor agonists such as 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 3. Tandospirone suppressed carbachol-stimulated phosphatidyl-inositol metabolism (PI response), which was shown to be a 5-HT1A receptor-mediated event. 4. Tandospirone did not affect the release of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine (ACh) from rat brain slice preparations. 5. These findings suggested that tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1A receptors but does not affect the presynaptic autoreceptors located on nerve endings. The modulation of the second messenger system via postsynaptic 5-HT1A receptors might be involved in the anxiolytic efficacy of tandospirone.
Gen Pharmacol 1995 Dec
PMID:Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain. 874 67

Autoradiographic studies were performed in combination with dorsal rhizotomy or selective lesion of descending serotonergic or noradrenergic systems in an attempt to identify the neuronal cell types endowed with the serotonin 5-HT1A, 5-HT1B and 5-HT3 receptors in the rat spinal cord. Unilateral sectioning of seven dorsal roots (C4-T2) at the cervical level produced a marked decrease (approximately-75%, 10 days after the surgery) in the binding of [125I]iodozacopride to 5-HT3 receptors in the superficial layers of the ipsilateral dorsal horn, further confirming the preferential location of these receptors on primary afferent fibres. In addition, a significant decrease (approximately 20%) in the binding of [3H]8-OH-DPAT to 5-HT1A receptors and of [125I]GTI to 5-HT1B receptors was also observed in the same spinal area in rhizotomized rats, suggesting that a small proportion of these receptors are also located on primary afferent fibres. The labelling of 5-HT1B receptors was significantly decreased (-12%) in the dorsal horn at the cervical (but not the lumbar) level, and that of 5-HT3 receptors was unchanged in the whole spinal cord in rats whose descending serotonergic projections had been destroyed by 5,7-dihydroxytryptamine. Conversely, the labelling of 5-HT1A receptors was significantly increased in the cervical (+13%) and lumbar (+42%) dorsal horn in 5,7-dihydroxytryptamine-lesioned rats. Similarly, [3H]8-OH-DPAT binding to 5-HT1A receptors significantly increased (+26%) in the lumbar (but not the cervical) dorsal horn in rats whose noradrenergic systems had been lesioned by DSP-4. The labelling of 5-HT1B receptors was also increased (+31% at the cervical level; +17% at the lumbar level), whereas that of 5-HT3 receptors remained unchanged in these animals. These data indicate that complex adaptive changes in the expression of 5-HT1A and 5-HT1B receptors occurred in the rat spinal cord following the lesion of descending monoaminergic systems.
J Neural Transm Gen Sect 1995
PMID:Effects of dorsal rhizotomy and selective lesion of serotonergic and noradrenergic systems on 5-HT1A, 5-HT1B, and 5-HT3 receptors in the rat spinal cord. 874 67

1. Behavioral responses to unilateral and bilateral microinjections of the 5-HT1A receptor antagonist, NAN190 [1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]piperazine hydrobromide] (1 microgram), into the hippocampal CA1 area of male Wistar rats were studied. 2. NAN190 decreased locomotor activity (the number of horizontal and vertical movements). The effect was most pronounced with microinjections of NAN190 into the right hippocampus. 3. Microinjections of NAN190 facilitated learning and memory in shuttle-box testing. 4. Microinjections of NAN190 had an anxiogenic effect in elevated plus-maze experiments and Vogel's conflict test. 5. The different behavioral responses to left and right microinjections of NAN190 in some of the behavioral tests suggest functional asymmetry of 5-HT1A receptors in the CA1 hippocampal area.
Gen Pharmacol 1997 Mar
PMID:Behavorial responses to the 5-HT1A receptor antagonist NAN190 injected into rat CA1 hippocampal area. 906 87

1. The behavioral responses, as well as the biogenic amines and metabolite contents in discrete brain areas were determined in male rats subcutaneously treated with a 5-HT1A (8-OHDPAT) or 5-HT2A (DOI) agonist at doses (0.5-2 mg/kg) sufficient to produce the typical effects of the stimulation of these brain receptor subtypes. 2. Besides the expected effects (i.e., forepaw treading, flat body posture and inhibition of 5-HT release and turnover), 8-OHDPAT displayed signs of increased dopaminergic transmission. 3. DOI increased dopamine turnover and provoked stereotypical behavior, in addition to head shakes and body twitches. 4. Moreover, DOI induced both forepaw treading and flat body posture, which are believed to be typical responses to the stimulation of brain 5-HT1A receptors. 5. This finding cannot be explained on the basis of actual knowledge, because the affinity of DOI for 5-HT1A receptor has been found to be very low, whereas indirect mechanisms of activation of this receptor subtype triggered by stimulation of 5-HT2A receptor are actually unknown.
Gen Pharmacol 1997 Apr
PMID:Effect of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and brain biogenic amines of rats. 914 28


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