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)

Catalepsy induced by neuroleptics in rats can be modified by 5-hydroxytryptaminergic (5-HTergic) manipulation. For example, buspirone (BUS) and other central 5-HT1A receptor ligands reduce neuroleptic-induced catalepsy (NIC). The dorsal (DRN) and median (MRN) raphe nuclei are reported to be important sources of 5-HTergic projections to the basal ganglia, the site of action of neuroleptics in producing NIC. A previous study showed that lesion of DRN did not affect NIC or the anticataleptic effect of BUS. The present study was designed to evaluate the participation of MRN in NIC and in the anti-NIC effect of BUS. Twenty-four male Wistar rats (N = 6/group) weighing 220-250 g were used. Electrolytic lesion of MRN was carried out in anesthetized rats along with sham operations (electrode inserted but no current applied). Ten days later, the rats were injected with BUS (5 mg/kg, ip) or saline (1 ml, ip). Catalepsy was induced 20 min later with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. The Costall & Naylor method of scoring (range 0-5 points) was used. Saline-injected MRN-lesioned rats displayed significantly lower catalepsy scores than sham-lesioned rats (1.5 +/- 0.2 vs 3.8 +/- 0.3 at 90 min after H). In sham-lesioned rats, BUS significantly reduced the catalepsy scores in comparison with saline-treated animals (1.3 +/- 0.2 vs 3.8 +/- 0.3 at 90 min after H). However, BUS was not able to further reduce NIC in the MRN-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of median raphe nucleus lesions on neuroleptic-induced catalepsy and on the anticataleptic effect of buspirone. 790 58

This experiment was designed to elucidate the neurotransmitter systems that mediate the discriminative stimulus effects of methamphetamine. Four pigeons were trained to peck one key following saline injections and a second key following methamphetamine injections (1.0 or 1.7 mg/kg, IM). Substitution tests revealed drug-appropriate responding following administration of the psychomotor stimulants methamphetamine, amphetamine and cocaine, the dopamine (DA) reuptake inhibitor bupropion, norepinephrine (NE) reuptake inhibitors imipramine and tomoxetine, and the serotonin (5-HT) releaser fenfluramine. Saline-key responding occurred following administration of the D1 agonist SKF-38393, the D1 antagonist SCH-23390, the alpha 2 receptor agonist clonidine, the alpha 1 antagonist prazosin, a nonselective beta-antagonist propranolol and the selective 5-HT reuptake inhibitor fluoxetine. The D2/D3 agonist quinpirole produced drug-appropriate responding in two pigeons and partial substitution in the remaining two pigeons. The 5HT1A agonist 8-OH-DPAT produced drug-appropriate responding at higher doses (0.3-1.0 mg/kg), whereas much lower doses (0.003-1.0 mg/kg) antagonized the methamphetamine stimulus. The stimulus effects of methamphetamine were attenuated by pretreatment with prazosin, SCH-23390 and eticlopride, whereas pretreatment with propranolol and the 5-HT3 antagonist, MDL 72222, failed reliably to attenuate drug key responding. These results suggest that NE and DA reuptake inhibition and 5-HT release mediate the discriminative stimulus effects of methamphetamine as do the 5-HT1A and DA D1 and D2 receptors.
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PMID:The discriminative stimulus effects of methamphetamine in pigeons. 852 78

The present results show that under constant darkness the endogenous circadian pacemaker located in the suprachiasmatic nuclei can be affected by administration of 8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), a well known 5-HT1A/5-HT7 receptor agonist. A single i.p. injection (0.1 ml) with 8-OH-DPAT (5 mg/kg) induced significant phase-advances of hamster locomotor activity at circadian time (CT) 6 and 8 and a significant phase-delay at CT11. Saline injections by themselves induced a significant phase-advance at CT10-11. The dose-response curve for 8-OH-DPAT showed a maximal phase-shifting effect for doses of at least 2.5 mg/kg at CT8. Thus, in golden hamsters. (1) 8-OH-DPAT has a chronobiological effect with sensitivity depending upon the circadian time of injection, and (2) a single saline injection is able to induce regular phase-advances at the end of the subjective day (CT10-11).
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PMID:Phase-shifting effect of 8-OH-DPAT, a 5-HT1A/5-HT7 receptor agonist, on locomotor activity in golden hamster in constant darkness. 876 77

The rat posterodorsal medial amygdala (MePD) is a component of the neural network that modulates male sexual behavior. Dendritic spines were counted in Golgi-impregnated bitufted and stellate neurons and from cells located in the medial and lateral MePD subregions. It was also studied the effect of 8-OH-DPAT, a 5-HT1A receptor agonist, microinjected into the MePD on male sexual behavior. There were no significant differences in the dendritic spine density obtained from multipolar bitufted and stellate neurons (n = 48 cells in each group; p > 0.05) or in the data from the medial or the lateral MePD (n = 48 neurons per region; p > 0.05). Rats were stereotaxically microinjected into the MePD with saline (0.2 microl, n = 6) or 8-OH-DPAT (0.1 and 1.0 microg/0.2 microl, n = 6 and 5, respectively). Behavioral recordings prior to surgery and "non-target" microinjections served as additional control data. 8-OH-DPAT 1.0 microg decreased the latencies to intromission and ejaculation, the postejaculatory refractory period and the mount frequency when compared to control pre-surgery data (p < 0.05). When compared among groups, 8-OH-DPAT 1.0 microg promoted the highest percentage reduction in the postejaculatory refractory period. Saline and injections in the vicinity of MePD did not promote relevant effects on ejaculation (p > 0.05). Results indicate that a similar dendritic spine density can be found in morphologically different populations of MePD neurons and, 8-OH-DPAT can facilitate male sexual behavior by acting on postsynaptic 5-HT1A receptors in this brain area.
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PMID:Further studies on the rat posterodorsal medial amygdala: dendritic spine density and effect of 8-OH-DPAT microinjection on male sexual behavior. 1653 61

Antidepressants may be effective treatment for smoking cessation and new evidence on relationship between smoking and depression is emerging. Extracts of the plant Hypericum perforatum possess antidepressant activity in humans and reduce nicotine withdrawal signs in mice. Both nicotine and H. perforatum administration elicit changes in serotonin (5-HT) formation in the brain. On this basis, we investigated the possible involvement of 5-HT in the beneficial effects of H. perforatum on nicotine withdrawal signs. With the aim to induce nicotine dependence, nicotine (2 mg/kg, four intraperitoneal injections daily) was administered for 14 days to mice (NM). Saline (controls, M) or H. perforatum extract (Ph 50, 500 mg/kg) were orally administered immediately after the last nicotine injection for 30 days after nicotine withdrawal. Another group of animals treated with nicotine (14 days) and successively with H. perforatum extract was intraperitoneally co-administered with selective 5-HT receptorial antagonist WAY 100635 (WAY) (1 mg/kg). All animals were evaluated for locomotor activity and abstinence signs, 24 after nicotine withdrawal. Brain 5-HT metabolism was evaluated in the cortex of mice sacrificed 30 days after nicotine withdrawal through evaluation of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio. After nicotine withdrawal measurement of 5-HT metabolism in the cortex showed a reduction of 5-HT content while animals treated only with Hypericum extract showed a significant reduction of total abstinence score compared to controls. WAY inhibited the reduction of total abstinence score induced by H. perforatum. Moreover, 5-HT1A expression has been evaluated 30 days after nicotine withdrawal. Our results, show a significant increase of cortical 5-HT content in NM treated with H. perforatum, with a concomitant significant increase of 5-HT1A receptor. So, it is possible to suggest an involvement of 5-HT in beneficial effects of H. perforatum on suffering produced by nicotine withdrawal in dependent mice.
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PMID:Serotonin mediates beneficial effects of Hypericum perforatum on nicotine withdrawal signs. 1768 33

Schizophrenia pathophysiology is associated with alterations in several neurotransmitter systems, particularly dopamine, glutamate and serotonin (5-HT). Schizophrenia patients also have disruptions in sensory gating, a brain information filtering mechanism in response to repeated sensory stimuli. Dopamine and glutamate have been implicated in sensory gating; however, little is known about the contribution of serotonin. We therefore investigated the effects of several psychoactive compounds that alter serotonergic neuronal activity on event-related potentials (ERP) to paired auditory pulses. Male Sprague-Dawley rats were implanted with cortical surface electrodes to measure ERPs to 150 presentations of two 85 dB bursts of white noise, 500 ms apart (S1 and S2). Saline-treated animals suppressed the response to S2 to less than 50% of S1. In contrast, treatment with the serotonin releaser, MDMA (ecstasy; 2.0mg/kg), the 5-HT2A/2C receptor agonist, DOI (0.5mg/kg), or the 5-HT1A/7 receptor agonist, 8-OH-DPAT (0.5mg/kg), caused an increase in S2/S1 ratios. Analysis of waveform components suggested that the S2/S1 ratio disruption by MDMA was due to subtle effects on the ERPs to S1 and S2; DOI caused the disruption primarily by reducing the ERP to S1; 8-OH-DPAT-induced disruptions were due to an increase in the ERP to S2. These results show that 5-HT receptor stimulation alters S2/S1 ERP ratios in rats. These results may help to elucidate the sensory gating deficits observed in schizophrenia patients.
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PMID:Schizophrenia-like disruptions of sensory gating by serotonin receptor stimulation in rats: effect of MDMA, DOI and 8-OH-DPAT. 2412 Jul 65