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)

This study examined the consequences of elevated corticosterone levels in lactating rats on their offspring's serotonergic 5-hydroxytryptamine (5-HT)1A receptor system and behavioral coping with stress. The mothers received normal drinking water or water with corticosterone, which, via the milk, enters the circulation and brains of the pups. In adulthood, the corticosterone-nursed offspring showed a consistently more passive way of coping with environmental challenges. However, they did not seem to be more anxious. Autoradiographic analysis of the 5-HT1A receptor system revealed a decrease in the adult 5-HT1A receptor binding in the hippocampal CA1 region. The results support the hypothesis that differences in behavioral coping with stress by adult rats are associated with differences in the serotonergic system. At the same time, it suggests that adult coping and its neuronal substrates are not solely determined by genes but depend on subtle developmental factors as well.
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PMID:Increased maternal corticosterone levels in rats: effects on brain 5-HT1A receptors and behavioral coping with stress in adult offspring. 1158 24

Using an animal model of drug relapse, we found that intermittent footshock stress reinstates alcohol seeking, an effect attenuated by the 5-HT reuptake blocker fluoxetine and by corticotropin-releasing factor (CRF) receptor antagonists. Here we studied the role of the 5-HT cell body region of the median raphe nucleus (MRN) and CRF receptors in this site in reinstatement of alcohol seeking. Rats were given alcohol in a two-bottle choice procedure (water vs alcohol) for 25 d and were then trained for 1 hr/d to press a lever for alcohol (12% w/v) for 23-30 d. Subsequently, lever pressing for alcohol was extinguished by terminating drug delivery for 5-9 d. Tests for reinstatement of alcohol seeking were then performed under extinction conditions. Intra-MRN infusions of 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] (a 5-HT1A agonist that decreases 5-HT cell firing and release) reinstated alcohol seeking. Reinstatement of alcohol seeking also was observed after intra-MRN infusions of low doses of CRF (3-10 ng), which mimicked the effect of ventricular infusions of higher doses of the peptide (300-1000 ng). Finally, intra-MRN infusions of the CRF receptor antagonist d-Phe CRF (50 ng) blocked the effect of intermittent footshock (10 min) on reinstatement. These data suggest that an interaction between CRF and 5-HT neurons within the MRN is involved in footshock stress-induced reinstatement of alcohol seeking.
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PMID:The role of corticotropin-releasing factor in the median raphe nucleus in relapse to alcohol. 1222 36

Serotonin plays an important role in the regulation of food and water intake, and drugs that inhibit the uptake of this neurotransmitter have been used as appetite suppressors. As the clinical usage of anorectics necessarily involves chronic drug administration, the effects of chronic treatment in animals are likely to be of greater clinical relevance than acute drug effects. Besides, little effort has been made to examine whether these effects interact with stressful situations, such as isolation. We have therefore examined the effects of fluoxetine, a selective 5-HT reuptake inhibitor, and gepirone, a 5-HT1A agonist, on body weight in isolated and in group-housed rats during 3 weeks of daily treatment. Gepirone caused an increase in body weight only in isolated rats. On the other hand, fluoxetine caused a significant reduction in body weight in both singly- and group-housed animals. The effects of these serotonergic agents were more prominent during the first week of treatment. From the data obtained in this study, it is suggested that increased 5-HT transmission produced by fluoxetine during chronic administration seems to be crucial for the appetite-regulating action of 5-HT, and this hypophagic effect does not seem to be dependent on the activation of 5-HT1A receptors since it was not shared by gepirone. Moreover, a concomitant stressful situation, such as isolation, interferes with the action of gepirone on feeding behavior. The hyperphagic effects of chronic regimen with gepirone in isolated animals are probably due to the concurrent reduction of the 5-HT transmission caused by this anxiogenic condition at the earlier stages of treatment. On the other hand, the anorectic effects of fluoxetine do not seem to interact with the stressful situations caused by isolation.
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PMID:Influence of housing conditions on the effects of serotonergic drugs on feeding behavior in non-deprived rats. 1270 93

Radiolabeled FCWAY (N-(2-[4-(2-methoxyphenyl)piperazino])-N-(2-pyridinyl) trans-4-fluorocyclohexanecarboxamide) was prepared for human positron emission tomography (PET) studies by a simple one-step radiosynthesis. The LC-MS analysis of the products indicated that it contained impurities which may interfere with FCWAY uptake of 5-HT1A receptors and that these impurities were derived from an impurity originally present in the precursor preparation. Since preparative HPLC failed to resolve one of the impurities from the precursor, preparative-scale high-speed counter-current chromatography (HSCCC) was used for purification of this FCWAY precursor. A suitable two-phase solvent system composed of cyclohexane-ethyl acetate-methanol-water at a volume ratio of 1:1:1:1 or 4:5:4:5 was selected based on the partition coefficients of the precursor and impurity as determined by a LC-MS method. Using the second solvent ratio of 4:5:4:5 with the organic phase as a mobile phase, a 2.57 g amount of precursor preparation was successfully purified yielding 2.2 g of the pure precursor by a single run.
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PMID:Purification of the precursor for the automated radiosynthesis of [18F]FCWAY by counter-current chromatography. 1511 24

The serotonin (5-hydroxytryptamine, 5-HT) receptor 1A is involved in many physiological functions, including the regulation of learning and memory by acting either as an autoreceptor located on 5-HT neurons (raphe nuclei) or as a heteroreceptor on non-5-HT neurons, mainly in the hippocampal formation. To investigate whether the effects of 5-HT via 5-HT1A receptors on learning are age-sensitive, we evaluated the performance of young-adult (3 months old) and aged (22 months old) 5-HT1A knockout (KO) mice and their homologous wild types (WT) in the hippocampal-dependent spatial reference memory version of the Morris water maze. We demonstrated that young-adult 5-HT1AKO mice exhibit an impairment in learning and retention of the spatial task, as compared to WT mice, without showing any sign of change in their sensori-motor and locomotor abilities or motivation. This genotype effect does not persist during aging. In fact, aged 5-HT1AKO mice seem to be slightly facilitated during the early stages of learning. These results are consistent with a possible prevalence of 5-HT1A raphe functions in learning and memory abilities of young-adult animals, since the effects of the mutation on mice performance (impairment) are opposite to those found after intra-raphe injection of 5-HT1A agonists (facilitation), and with data showing increased activity of 5-HT neurons in 5-HT1AKO mice. The reduced effect of the mutation in aged animals possibly reflects the lower efficacy of autoreceptors due to aging and/or a prevalence of hippocampal heteroreceptors.
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PMID:Age-dependent effects of serotonin-1A receptor gene deletion in spatial learning abilities in mice. 1551 75

This study examined the distribution of 5-HT-immunoreactive perikarya (5-HT-IRp) and the effects of local injections of 8-OH-DPAT into 5-HT-IRp-containing pontine and mesencephalic regions on feeding and drinking behaviors in free-feeding pigeons. When infused into the midline 5-HT-IRp-containing areas, 8-OH-DPAT (6.1 nmol) reliably elicited drinking and, to a lesser extent, feeding responses during the first hour after injection. These responses were significantly higher than the ingestive indexes observed (1) after vehicle (ascorbic acid 0.1%, 200 nl) injections at the same sites and (2) after 8-OH-DPAT injections into adjacent sites devoid of 5-HT-IRp. Increases in drinking were proportionally higher than those observed in feeding and a significant negative correlation was observed between water and food after midline 8-OH-DPAT injections. Similar dipsogenic responses were observed after injections of different 8-OH-DPAT doses (0.6, 2.0, and 6.1 nmol). Pretreatment with local injections of p-MPPI (an antagonist of 5-HT1A receptors) attenuated the ingestive responses evoked by 8-OH-DPAT injections. Injections of 8-OH-DPAT into lateral 5-HT-IRp-containing sites evoked only inconsistent and weak ingestive responses. These results indicate that 5-HT1A receptor-mediated circuits located in the midline superior raphe system of the pigeon may play an important role in mechanisms controlling water intake, similar to that observed in mammals.
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PMID:Behavioral effects of 8-OH-DPAT injections into pontine and mesencephalic areas containing 5-HT-immunoreactive perikarya in the pigeon. 1572 55

The role of the brain 5-HT1A receptor in cognition was examined in the water maze (WM) and passive avoidance (PA) tasks in the male rat. Pre-training administration of the 5-HT1A receptor agonist 8-OH-DPAT impaired WM performance and facilitated PA retention at low doses (0.01 and 0.03 mg/kg) and impaired PA retention at higher doses (0.1-1.0 mg/kg). The 5-HT1A receptor antagonist NAD-299 produced a dose-dependent facilitation of PA retention. In contrast, the 5-HT1A receptor antagonists NAD-299 and WAY-100635 failed to alter acquisition and retention in the WM. The impairments in WM and PA (but not facilitation in PA) induced by 8-OH-DPAT were blocked by NAD-299. Furthermore, NAD-299 prevented the PA impairments induced by the muscarinic antagonist scopolamine or the NMDA receptor antagonist MK-801. In contrast, NAD-299 and WAY-100635 failed to attenuate the WM impairment induced by scopolamine, probably due to the failure of 5-HT1A receptor blockade to attenuate the sensorimotor disturbances induced by scopolamine. These results indicate that 5-HT1A receptor stimulation and blockade result in opposite effects in two types of cognitive tasks in the rat, and that 5-HT1A receptor blockade can facilitate some aspects of cognitive function, probably via modulation of cholinergic and glutamatergic transmissions. This suggests that 5-HT1A receptor antagonists may have a potential role in the treatment of human degenerative disorders associated with cognitive deficits.
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PMID:Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat. 1582 55

Serotonin is known to inhibit food and water intake. However, the effect of its injection into nucleus caudatus on food and water intake is not known. In the present study, serotonin hydrochloride, buspirone (the serotonin 5-HT1A agonist) and ondensetron (the 5HT3 antagonist) were injected into nucleus caudatus through stereotaxically implanted cannulae in three different dosages (1, 2 and 5 microg) and their effects on 24 h food and water intake, and body weight were recorded. The injection of serotonin hydrochloride resulted in a dose- dependent decrease in food intake attaining maximum of 27.3% at 5 microg dose, whereas water intake and body weight were decreased 12% and 4.3% respectively only at the highest does. Buspirone elicited a dose dependent inhibition of food and water intake and body weight (22.3%, 19.8% and 5.1% respectively), whereas ondensetron elicited an increase in food and water intake (37.8% and 36.3% respectively) without significantly altering bodyweight. It was concluded that serotonin hydrochloride injected into nucleus caudatus inhibits food and water intake significantly. These effects are mediated via 5-HT1A and 5HT3 receptors. The effect of injections of 5-HT1A receptor agonist is more pronounced on water intake. The effect of injections of 5HT3 receptor antagonist is also more pronounced on water intake.
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PMID:Effects of injection of serotonin into nucleus caudatus on food and water intake and body weight in albino rats. 1590 52

The present study was performed to examine the effects of electroacupuncture (EA) on cold allodynia and its mechanisms related to the spinal adrenergic and serotonergic systems in a rat model of neuropathic pain. For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, EA stimulation (2 or 100 Hz) was delivered to Zusanli (ST36) for 30 min. The behavioral signs of cold allodynia were evaluated by the tail immersion test [i.e., immersing the tail in cold water (4 degrees C) and measuring the latency to an abrupt tail movement] before and after the stimulation. And then, we examined the effects of intrathecal injection of prazosin (alpha1-adrenoceptor antagonist, 30 microg), yohimbine (alpha2-adrenoceptor antagonist, 30 microg), NAN-190 (5-HT1A antagonist, 15 microg), ketanserin (5-HT2A antagonist, 30 microg), and MDL-72222 (5-HT3 antagonist, 12 microg) on the action of EA stimulation. Although both 2 Hz and 100 Hz EA significantly relieved the cold allodynia signs, 2 Hz EA induced more robust effects than 100 Hz EA. In addition, intrathecal injection of yohimbine, NAN-190, and MDL-72222, but not prazosin and ketanserin, significantly blocked the relieving effects of 2 Hz EA on cold allodynia. These results suggest that low-frequency (2 Hz) EA is more suitable for the treatment of cold allodynia than high-frequency (100 Hz) EA, and spinal alpha2-adrenergic, 5-HT1A and 5-HT3, but not alpha1-adrenergic and 5-HT2A, receptors play important roles in mediating the relieving effects of 2 Hz EA on cold allodynia in neuropathic rats.
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PMID:Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: mediation by spinal adrenergic and serotonergic receptors. 1605 38

The serotonergic system in the CNS has complex interactions with many, if not all other neurotransmitter systems in the brain. Its localization, distribution and amazing receptor diversity makes it an appealing system for modulatory aspects in many basic behaviours, including food and water intake, sexual behaviour and aggression. Notwithstanding decades of research into the putative role of the serotonergic system in aggression, no clear picture about its specific role has emerged. It seems, dependent on state or trait, to be involved in either the performance or the termination of aggressive behaviours. The present technology appears not developed enough to give answers to these questions. Application of drugs and particular selective ligands for certain subtype receptors seems a more promising approach to unravelling the role of 5-HT in aggression. The (postsynaptic) 5-HT1B and to a lesser extent, the 5-HT1A receptor seems to play a prominent role, at least in rodents, in the modulation of (offensive) aggression.
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PMID:Serotonergic mechanisms in aggression. 1620 80


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