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)

It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HT1A receptors located in the hippocampus participate in the development of tolerance to aversive events.
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PMID:Hippocampal 5-HT receptors and consolidation of stressful memories. 813 41

The role of lithium in treating bipolar affective disorder is poorly understood; however, it may involve effects on brain 5-HT function. We have shown that the 5-HT2A/2C receptor agonist DOI (2,5-dimethoxy-4-iodophenylisopropylamine) induces the expression of c-fos in rat brain which correlates with the distribution of 5-HT2A receptors. We now report on the effect of lithium on 5-HT receptor activation. Rats were treated chronically with dietary lithium before being given either DOI or the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), and their brains were processed for c-fos immunohistochemistry. Lithium treatment greatly enhanced levels of Fos seen after DOI, but not after 8-OH-DPAT; layer II of caudal piriform cortex, previously devoid of staining, exhibited the most marked labelling. This suggests that chronic lithium selectively alters immediate-early gene expression in brain. Such alteration may underlie the action of lithium in treating bipolar affective disorder.
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PMID:Lithium enhances 5-HT2A receptor-mediated c-fos expression in rat cerebral cortex. 829 81

SM-9018 (cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl) hexahydro-1 H-isoindole-1,3(2H)-dione HCl) is a potential atypical antipsychotic with high affinity for 5-HT2, dopamine D2 and 5-HT1A receptors. Northern blot analysis was performed to compare the effects of SM-9018 and of haloperidol on the striatal c-fos mRNA expression in rats. Haloperidol (0.3-30 mg/kg, p.o.) markedly increased the striatal c-fos mRNA levels (about eight-fold at 30 mg/kg), the increase being abolished by lesioning of dopamine neurons with 6-hydroxydopamine. In contrast, SM-9018 produced only a slight increase (about two-fold) in c-fos mRNA expression at doses up to 30 mg/kg (p.o.). The 5-HT2 receptor antagonist, ritanserin (0.1-3 mg/kg, i.p.), dose-dependently attenuated the haloperiodol-induced c-fos expression, but the putative 5-HT1A receptor antagonist, NAN-190 (1-(2-methoxyphenyl)-4-(4-(2-phethalimmido)butyl)piperazine HBr; 1-10 mg/kg, i.p.), did not. These findings suggest that SM-9018 is weaker than haloperidol for induction of striatal c-fos mRNA expression, to which the 5-HT2 receptor blocking activity of SM-9018 seems to contribute.
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PMID:Contrasting effects of SM-9018, a potential atypical antipsychotic, and haloperidol on c-fos mRNA expression in the rat striatum. 881 76

The functional profiles of brain 5-HT1A and 5-HT2A/C receptors were assessed by quantitating changes in the immediate early genes -c-fos, ngf1c and tis1, following receptor activation with either 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). Stimulation of either class of 5-HT receptor elicited an induction of all three immediate early genes to varying extents in cortex, hippocampus and cerebellum, but not in striatum. The responses to 8-OH-DPAT peaked earlier than those to DOI. WAY 100135 (N-tertiobutyl-3-[4-(2-methoxyphenyl)-piperazinyl]-2-phenylpropana mide), the putative 5-HT1A receptor antagonist blocked the 8-OH-DPAT effect but not the responses to DOI. WAY 100135 by itself also elicited a relatively smaller genomic response. Ketanserin completely abolished the DOI-induced genomic responses. The results support the earlier findings that 5-HT1A receptor sites are abundant in frontal cortex and hippocampus. In addition, the robust genomic responses to 8-OH-DPAT as well as Northern hybridization with a cDNA probe for 5-HT1A mRNA in the cerebellum clearly implicate the functional expression of 5-HT1A receptors in this brain region. The responses to the 5-HT2 receptor agonist, DOI support a greater abundance of these receptors in the cortex, and relatively lower levels in hippocampus and cerebellum. The results suggest a differential induction pattern among the three immediate-early genes depending on the brain region and the 5-HT receptor subtype involved.
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PMID:Genomic responses to 5-HT1A or 5-HT2A/2C receptor activation is differentially regulated in four regions of rat brain. 883 23

The mammalian suprachiasmatic nuclei (SCN) contain a circadian clock which is regulated by neuronal photic and non-photic afferences. Among these, the serotonergic input originating from the dorsal raphe nucleus (DRN) is extremely important. In rats, a light pulse administered during the dark period is known to induce the expression of the immediate early gene c-fos and to increase melatonin receptor density in the SCN. The aim of this study was to assess whether, in rats, these two phenomena were regulated by serotonin, acting via 5-HT1A receptors. Three days after pinealectomy, 4 groups of rats were injected i.p. 90 min before sacrifice with respectively: (1) vehicle, (2) the 5-HT1A-agonist 8-OH-DPAT (5 mg/kg), (3) the 5-HT1A-antagonist NAN-190 (10 mg/kg) or (4) NAN-190 and the 8-OH-DPAT. Half of the animals from each group were exposed to light for 60 min before sacrifice and the other half remained in darkness. Sacrifice took place 5 to 6 h after lights off. Our results show that the antagonist NAN-190: (1) completely blocked the photically-induced increase of melatonin receptor density in the SCN, with an IC50 = 0.352 +/- 0.103 mg/kg, and (2) partially blocked (30%) the photic induction of Fos (the protein product of c-fos) in the ventrolateral subdivision of the SCN. The agonist 8-OH-DPAT enhanced the photically-induced increase of melatonin receptors by 10% and decreased the photically-induced increase in Fos by 18%. Both drugs were devoid of any effect in non-light exposed animals. From these results we may suggest that, in rats, there is a serotonergic control of the neuronal path driving photic information to the SCN. This regulation seems to occur through 5-HT1A or 5-HT1a-like receptors.
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PMID:Serotonergic modulation of photically induced increase in melatonin receptor density and Fos immunoreactivity in the suprachiasmatic nuclei of the rat. 893 61

1. Previous experiments have suggested a potential atypical antipsychotic activity of the ergoline derivative LEK-8829. In vitro experiments showed a high affinity to 5-HT1A, 5-HT2 and D2 receptors (the ratio of pKi values 5-HT2/D2 = 1.11) and a moderate affinity to D1 receptors. In vivo experiments showed antagonism of dopamine and 5-hydroxytryptamine (5-HT) receptor-linked behaviours. 2. In the present study, the rats with unilateral dopaminergic deafferentation of the striatum, induced by the lesion of the median forebrain bundle with 6-hydroxydopamine (6-OHDA), were used to determine the effects of LEK-8829 on turning behaviour and on striatal c-fos mRNA levels. 3. The administration of LEK-8829 induced a long lasting contralateral turning behaviour that was dose-dependent. It was found that the specific D1 receptor antagonist SCH-23390 but not the D2 receptor antagonist haloperidol or 5-HT1A antagonist pindolol, dose-dependently inhibited the turning behaviour induced by LEK-8829. 4. In an attempt to clarify the D1:D2 receptor interactions involved in the action of LEK-8829 in the 6OHDA model, we used in situ hybridization histochemistry to compare the effect of SCH-23390 pretreatment on striatal c-fos mRNA expression induced either by LEK-8829 or by the typical antipsychotic haloperidol. 5. LEK-8829 induced a bilateral striatal c-fos mRNA expression that was significantly higher in the denervated striatum as compared to the intact striatum and was completely blocked on both sides by pretreatment with SCH-23390. In contrast, haloperidol-induced striatal c-fos mRNA expression was limited to the innervated striatum and was not blocked by SCH-23390. 6. Our data demonstrate an intrinsic activity of LEK-8829 on D1 receptors that is potentiated in the dopamine-depleted striatum. We conclude, therefore, that the putative atypical antipsychotic LEK-8829 may prove useful as an experimental tool for the study of D1:D2 receptor interactions and could have beneficial effects in the treatment of drug-induced psychosis in patients with Parkinson's disease.
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PMID:The D1 receptor-mediated effects of the ergoline derivative LEK-8829 in rats with unilateral 6-hydroxydopamine lesions. 893 22

The azapirones, which are partial agonists of the serotonin (5-HT)1A receptor, possess anxiolytic activity. These agents may act at the pre- or postsynaptic 5-HT1A receptors, and involve the noradrenergic system. To determine whether these drugs activate noradrenergic neurons via 5-HT1A receptors, we have evaluated the expression of the immediate early gene c-fos in the locus coeruleus. Tandospirone and ipsapirone each induced expression of Fos protein in the noradrenergic neurons of the locus coeruleus of conscious rats. This effect was reversed by pretreatment with (+)-WAY100135, a specific 5-HT1A antagonist. These results clearly demonstrate that azapirones activate noradrenergic neurons via 5-HT1A receptors.
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PMID:Serotonin1A receptor agonists induce Fos protein expression in the locus coeruleus of the conscious rat. 921 75

D-Fenfluramine is a serotonin (5-hydroxytryptamine, 5-HT) releaser and reuptake inhibitor. It is used to study the neurochemical control of feeding and has been used to treat obesity. It has also been employed as a pharmacological tool to study changes in serotonergic function in psychiatric patients. Brain sites activated by D-fenfluramine via the release of 5-HT have been mapped via the expression of the immediate early gene c-fos. Studies in our laboratory have indicated that D-fenfluramine induces Fos in the hypothalamus and cortex through 5-HT release. The present study investigated whether 5-HT released by D-fenfluramine induces Fos expression in the brain by activating 5-HT1A or 5-HT2A/2C receptors. Rats were pretreated either with WAY-100635, a 5-HT1A antagonist, or ritanserin, a 5-HT2A/2C antagonist, prior to d-fenfluramine injection. Blockade of either 5-HT1A or 5-HT2A/2C receptors was not sufficient to suppress the Fos response to D-fenfluramine in any region of the brain examined, including the cingulate cortex, frontal cortex, caudate-putamen, paraventricular nucleus of the hypothalamus, amygdala, and brainstem. These results indicate that Fos response elicited by D-fenfluramine may be mediated by other receptors, in addition to the 5-HT1A or 5-HT2A/2C receptors.
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PMID:The 5-HT1A and 5-HT2A/2C receptor antagonists WAY-100635 and ritanserin do not attenuate D-fenfluramine-induced fos expression in the brain. 959 27

Neural activation following sexual behavior was studied in the male and female rat brain, using Fos-immunoreactivity (Fos-IR) as a measure. In accordance with the available literature, we observed increased expression of c-fos in the medial preoptic nucleus (MPN), in the posteromedial subdivision of the bed nucleus of the stria terminalis, in the posterodorsal part of the medial amygdala, and in the caudal thalamus, in the parvicellular part of the subparafascicular nucleus. After performance of different behavioral elements (anogenital investigation, mounting, intromission or ejaculation) not only the numbers of Fos-IR neurons varied considerably, but also their distribution. Especially after ejaculation, but in females already after intromissions, dense groups of Fos-IR neurons appeared in specific subdivisions of the areas mentioned above. That these groups of dense Fos-IR appeared as a result of the ejaculation per se, was assessed by administrating the 5-HT1A agonist 8-OH-DPAT to the males, whereupon they ejaculated within a few seconds, without the usual amount of preceding behavioral elements. Since the pattern of Fos-IR was similar to the normal ejaculation pattern, we have described the dense activation areas as 'ejaculation-related clusters'. Our review discusses the stimuli and pathways probably involved in the observed pattern of Fos-IR and we conclude that the 'deep viscero-genital' activation, occurring at the moment of ejaculation, running along the pelvic nerve and ascending from the spinal cord, is most probably responsible. We show that the location of the Fos-IR neurons in the medial subparafascicular nucleus perfectly coincides with the location of Galanin-IR fibers, ascending from the spinal cord. The application of anterograde and retrograde neuroanatomical tracers into the MPN, in combination with Fos-IR showed that the medial preoptic nucleus has very specific relationships with the Fos-IR sub-areas, involved in ejaculation. We conclude that within the larger brain structures involved in sexual and other social activities, a specific ejaculation-related subcircuit exists, which may, under normal conditions in the rat, serve a 'sexual-satiety function'.
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PMID:Neural activation following sexual behavior in the male and female rat brain. 963 60

Fenfluramine, a serotonin releaser and uptake inhibitor, has been widely prescribed as an appetite suppressant. Despite its popular clinical use, however, the precise neural pathways and specific 5-HT receptors that account for its anorectic effect have yet to be elucidated. To test the hypothesis that stimulation of 5-HT1B receptors is required for the anorectic effect of fenfluramine, we assessed food intake in wild-type and 5-HT1B knock-out mice. Next, to determine possible brain structures and pathways that may contribute to the 5-HT1B-mediated effects of fenfluramine, we studied by immunohistochemistry the induction of the immediate early gene c-fos. Although the effect of fenfluramine on locomotion was indistinguishable between both wild-type and 5-HT1B knock-out mice, the anorectic effect of the drug was absent in only the knock-out mice. Furthermore, the induction of c-Fos immunoreactivity found in the paraventricular nucleus of the hypothalamus (PVN) of wild-type mice was substantially reduced in the knock-outs. Induction in the central amygdaloid nucleus (CeA) and in the bed nucleus of the stria terminalis (BNST), although robust in wild-type animals, was completely absent in knock-out animals. The mixed 5-HT1A/1B agonist RU24969 was able to mimic both the hypophagia and c-fos induction elicited by fenfluramine in wild-type mice, but not in the 5-HT1B knock-out mice. Our results thus demonstrate that stimulation of 5-HT1B receptors is required for fenfluramine-induced anorexia and suggest a role for the PVN, CeA, and BNST in mediating this effect.
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PMID:Absence of fenfluramine-induced anorexia and reduced c-Fos induction in the hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out mice. 965 Dec 34


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