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 study was designed to examine possible interactions between exogenous CCK and the 5-HT1A receptor subtype mediated serotonergic effects on feeding in rats. The somatodendritic 5-HT1A receptor agonist 8-OH-DPAT (0.32 mg/kg sc) evoked feeding in freely feeding rats. This effect was attenuated by treatment with CCK-8 (1, 5 and 25 micrograms/kg ip). In food deprived rats, CCK-8 (40 micrograms/kg ip) significantly reduced the size of a test meal. Treatment with the 5-HT1A receptor antagonist WAY-100135 (10 mg/kg ip) antagonized this anorectic effect of CCK-8. WAY-100135 on its own did not affect food intake. These results suggest the involvement of the 5-HT1A receptor subtype in mediating 5-HT-CCK interactions in the control of food intake in rats.
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PMID:Evidence for the involvement of the 5-HT1A receptor in CCK induced satiety in rats. 760 73

The aim of the present study was to investigate whether the 5-HT1A receptor agonist 8-OH-DPAT, which previously has been shown to release oxytocin, also influences plasma levels of gastrointestinal and pancreatic hormones, and if so, whether such an effect is mediated by an oxytocinergic mechanism. For this purpose 8-OH-DPAT (0.5 mg/kg s.c.) was injected to male rats pretreated with the oxytocin receptor antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin (1 mg/kg s.c.), or vehicle. Thirty min after injection of 8-OH-DPAT, plasma levels of oxytocin were significantly increased. 8-OH-DPAT also increased insulin and decreased CCK and somatostatin levels, effects that were blocked by pretreatment with the oxytocin antagonist. Taken together, these data suggest that the effect of 8-OH-DPAT on plasma levels of insulin, somatostatin and CCK may be mediated by oxytocin. In previous experiments, we have shown that following i.c.v. application of oxytocin, plasma levels of insulin are increased through a cholinergic mechanism. In this study, 2 ng of oxytocin decreased plasma levels of CCK, gastrin and somatostatin, effects that were blocked by pretreatment with atropine. Since oxytocinergic fibers which originate in the PVN project to the DMX, we suggest that the effect on the release of insulin, CCK and somatostatin induced by the 5 HT1A receptor agonist 8-OH-DPAT may be mediated by an oxytocinergic activation of a vagal mechanism.
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PMID:The oxytocin receptor antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin inhibits effects of the 5-HT1A receptor agonist 8-OH-DPAT on plasma levels of insulin, cholecystokinin and somatostatin. 879 88

Recently, a number of studies have provided evidence suggesting that CCK and 5-HT interact in the control of food intake. However, the majority of these studies have relied on the administration of exogenous CCK to investigate potential interactions. The aim of the present study was to focus on the potential role of endogenous CCK in 5-HT-CCK interactions. Our prediction was that the CCKA antagonist, devazepide, alone would potentiate the hyperphagic effect of the 5-HT1A agonist, 8-OH-DPAT, in free-feeding rats. The results showed that devazepide, at a dose that had no intrinsic effect (1.0 mg/kg), did not enhance the hyperphagic effect of 8-OH-DPAT (100 and 300 micrograms/kg). This suggests that when serotonergic inhibitory activity is reduced by 5-HT1A-receptor stimulation, there is no compensatory increase of endogenous CCK activity to excite 5-HT neurons and thereby inhibit food intake.
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PMID:Lack of interaction between devazepide and 8-OH-DPAT-induced hyperphagia in the rat. 891 91

In the present study, we investigated the influence of blockade of the serotoninergic and histaminergic neurotransmitter system on the anorectic effect of IP-injected amylin in rats. In 12- or 24-h food-deprived rats, blockade of central and peripheral serotonin (5-HT) receptors with the 5-HT1 and 5-HT2 receptor antagonist metergoline (0.5 or 0.05 mg/kg, IP, respectively) did not seem to influence the anorectic effect of IP injected amylin (1 microgram/kg). Similarly, inhibition of 5-HT synthesis and release with the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (200 micrograms/kg, IP) did not diminish amylin's (5 micrograms/kg, IP) anorectic effect in 24-h food-deprived rats whereas that of CCK (3 micrograms/kg, IP) was blocked under comparable conditions. Pretreatment of rats with the histamine H3 receptor agonists R-alpha-methylhistamine (MH: 3 mg/kg, IP) and Imerit (3 mg/kg, IP), which block transmission in the histaminergic system by inhibiting release of endogenous histamine, attenuated amylin's (1 microgram/kg) anorectic effect in 24-h food-deprived rats. These results suggest that the histaminergic system in involved in transduction of IP amylin's inhibitory effect on feeding in rats. In contrast, the serotoninergic system does not seem to be involved in mediating amylin's anorectic effect.
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PMID:The histaminergic, but not the serotoninergic, system mediates amylin's anorectic effect. 897 26

The influence of cholecystokinin (CCK-8S) and serotonin (5-HT) on the discharge rate of spontaneously active ventromedial hypothalamic (VMH) neurons was investigated in brain slices. Drugs were drop-applied individually and concomitantly into the slice chamber. CCK-8S (0.1-2.5 microM) produced a dose-dependent increase in firing rate mainly mediated by the CCK(B) receptor subtype, because Suc-CCK-4 (a CCK(B) receptor agonist) acted like CCK-8S and A-71378 (a CCK(A) receptor agonist) rarely induced excitatory effects. The main response to serotonin application (2-20 microM) was an inhibition that could be mimicked by 8-OH-DPAT (a 5-HT1A receptor agonist). S-UH-301 (a 5-HT1A receptor antagonist) reversibly diminished or blocked this effect. Other 5-HT agonists like DOI and 2-Methyl-5-HT did not evoke relevant responses. Co-administration of CCK-8S and 5-HT induced counteracting effects at which CCK-8S significantly reduced the prevailing suppressive effect of serotonin. It is concluded that both substances, CCK and 5-HT, have a reciprocal influence on the regulation of neuronal activity within the VMH, a structure, which is involved in the mediation of signals for the state of satiety.
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PMID:Interactive effects of cholecystokinin-8S and serotonin on spontaneously active neurons in ventromedial hypothalamic slices. 984 2

Although selective 5-hydroxytryptamine (5-HT) reuptake inhibitors (SSRIs) are widely used in the chronic treatment of several anxiety disorders, increased anxiety has been observed in some patients at the beginning of treatment with these compounds. Similar increases in anxiety-related behaviors have been observed in animal studies following a single injection with SSRIs. The mechanism underlying this effect is unclear. The aim of the present study was to investigate the effects of a variety of psychoactive compounds on the anxiogenic-like activity of fluoxetine. The drugs used included the benzodiazepine diazepam, the 5-HT1A receptor partial agonist buspirone, the 5-HT1A receptor antagonists pindolol and WAY-100635, the non-selective 5-HT2 receptor antagonists methiothepin, mianserin and ritanserin, the non-selective dopamine (DA) receptor antagonist haloperidol, the D1 antagonist SCH23390, the selective D2 antagonist raclopride, the D2/3 agonist quinelorane, the cholecystokininB (CCK(B)) receptor antagonist LY 288513, and the corticotropin-releasing factor1 (CRF1) receptor antagonist CP-154,526. Experiments were performed in the free-exploration test. This model is based on the strong neophobic reactions exhibited by BALB/c mice when confronted simultaneously with a familiar and a novel environment. When administered alone, diazepam (1 and 2 mg/kg), buspirone (1 mg/kg) and mianserin (0.3 mg/kg) produced anxiolytic-like effects as they significantly increased exploratory activity of the novel compartment. In contrast, fluoxetine (20 mg/kg) almost completely suppressed exploration of the novel area. Diazepam reversed the anxiogenic-like as well as the locomotor impairment induced by fluoxetine, while quinelorane blocked only the anxiogenic action of fluoxetine. None of the other compounds was able to counteract this effect. Taken together, these results suggest that dopaminergic mechanisms may underlie, at least in part, the behavioral effects of fluoxetine in the free-exploration test, whereas 5-HT1A 5-HT2, CCK(B) and CRF1 receptors may not be involved primarily in these effects.
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PMID:An investigation of the mechanisms responsible for acute fluoxetine-induced anxiogenic-like effects in mice. 1148 52

An overview of the preclinical literature on the effects of the most studied clinically effective or putative non-benzodiazepine anxiolytics in existing animal models of anxiety-like behavior indicates that, with the exception of 5-HT1A agonists, these compounds display highly variable effects. Because these drugs have been shown (selective 5-HT reuptake inhibitors) or proposed (CCK(B) and CRF antagonists) to have a different spectrum of therapeutic activity in anxiety disorders than benzodiazepines, agents mainly used against generalized anxiety disorder, the screening of such compounds clearly requires the validation of new techniques that may model aspects of these conditions.
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PMID:Rodent models of anxiety-like behaviors: are they predictive for compounds acting via non-benzodiazepine mechanisms? 1189 22

The basal ganglia in the brain contains glutamate, dopamine, serotonin, noradrenaline, CCK, adenosine, opioid, cannabinoid, etc. These agents contribute to keep motor control and modulation of the agent may be a cue to the treatment of movement disorders. D1 or D2 dopamine receptor agonists increase locomotor activity in MPTP-treated common marmosets which showed decreased locomotor activity and decreased number of dopamine neurons in the substantia nigra. Using this model of parkinsonism, NMDA receptor antag-onists, antimuscarinic receptor antagonists, 5-HT1A receptor agonists, adenosine receptor antagonists were showed to reverse the impaired movement of the model animals. The results may contribute to the development of new drugs for the treatment of Parkinson's disease.
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PMID:[The pharmacological and rational theory for the drug development of Parkinson's disease]. 1546 80