共查询到20条相似文献,搜索用时 15 毫秒
1.
Delgado M Caicoya AG Greciano V Benhamú B López-Rodríguez ML Fernández-Alfonso MS Pozo MA Manzanares J Fuentes JA 《European journal of pharmacology》2005,511(1):9-19
S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT1 agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT1 receptor agonist with 5-HT2A and 5-HT3)receptor antagonist activities that might be useful in a number of conditions associated with anxiety. 相似文献
2.
Michael Brüss Michael Bühlen Manfred Göthert Heinz Bönisch Jeanette Erdmann 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(4):455-458
The cDNA from a schizophrenic patient heterozygous for a mutation of the 5-HT1A receptor gene was used to clone the variant and wild-type DNA into a eukaryotic expression vector. The mutation was characterized by a base pair substitution (A G) at the first position of codon 28, leading to an Ile Val amino acid exchange. COS-7 cells were transfected with the cDNA of either the wild type or the variant 5-HT1A receptor. The potencies of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT), 5-HT and roxindole, and of the antagonists methiothepin and spiperone in inhibiting specific binding of [3H]8-OH-DPAT of the mutant and wild-type 5-HT1A receptor were determined. All five 5-HT1A receptor ligands concentration-dependently inhibited specific [3H]8-OH-DPAT binding to both the wild-type and the variant 5-HT1A receptor. The rank order of potency of the ligands in inhibiting [3H]8-OH-DPAT binding was identical at both receptors and was roxindole > 8-OH-DPAT > 5-HT > methiothepin > spiperone. This rank order is characteristic for 5-HT1A receptors. The negative logarithms of the concentrations required for 50% inhibition (pIC50 values) of the ligands at the mutant 5-HT receptor correlated highly significantly with those at the wild-type receptor (r = 0.995). It is concluded that the pharmacological profile of the mutant 5-HT1A receptor does not differ from that of the wild-type 5-HT1A receptor. 相似文献
3.
Lithium administration (LiCl, 10 mmol/kg, SC on day 1, followed by 3 mmol/kg twice daily subsequently) for 14 days to mice produced attenuation of the hypothermic response to injection of 8-hydroxy-2-(di-n-propyla-mino)tetralin (8-OH-DPAT, 0.5 mg/kg SC). Head twitch responses to the 5-HT-receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg IP) and to precursor loading with carbidopa (25 mg/kg, IP) and 5-hydroxytryptophan (100 mg/kg IP) were similarly attenuated. By contrast with this reduction of 5-hydroxytryptamine (5-HT) function mediated by the 5-HT1A and 5-HT2 receptor sub-types, repeated lithium administration had no effect on the motor response to a putative 5-HT1B receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969, 3 mg/kg IP). Alpha2 adrenoceptor function, assessed by the sedation response to clonidine (0.25 mg/kg, IP), was also attenuated by repeated lithium administration. It is proposed that these actions may explain the emergence of lithium as an adjunct to the treatment of refractory depressive illness. 相似文献
4.
5-HT7 receptors are involved in REM sleep and possibly in mood disorders. REM sleep suppression and antidepressant-like behavior is observed in 5-HT7−/− mice and in rats treated with 5-HT7 receptor antagonists. We recently demonstrated that pharmacological blockade of 5-HT7 receptors enhances REM sleep suppression and antidepressant-like behavior induced by citalopram in rodents. It has been hypothesized that the effect of citalopram on sleep is essentially mediated by the activation of 5-HT1A receptors. The present study investigates the impact of 5-HT7 receptor gene deletion on the effect of various reuptake inhibitors on REM sleep and probes the role of 5-HT1A receptors in this response. Three SSRIs (citalopram, fluoxetine and paroxetine) but not the tricyclic antidepressant desipramine had a significantly stronger REM sleep suppressive effect in 5-HT7−/− mice compared to 5-HT7+/+ mice. In contrast, REM sleep was similarly reduced in 5-HT7+/+ mice and 5-HT7−/− mice after treatment with the 5-HT1A receptor agonist ipsapirone. Furthermore, both 5-HT7+/+ and 5-HT7−/− mice displayed the same increase in REM sleep duration produced by the 5-HT1A receptor antagonist WAY-100635. These findings indicate that 5-HT7 receptor deletion augments the effect of various SSRIs on REM sleep suppression and that this effect is distinct from those mediated via 5-HT1A receptors. 相似文献
5.
The effects of antimanic agents, including lithium, carbamazepine, clonazepam and zotepine, on the postsynaptic 5-HT1A receptor-mediated behavioral and hypothermic responses induced by 8-OH-DPAT in rats, and on [3H]8-OH-DPAT binding to 5-HT1A receptors in the rat hippocampus were examined. Treatment with lithium (3 mEq/kg, IP) for 14 days enhanced forepaw treading, one component of the 5-HT behavioral syndrome induced by 8-OH-DPAT, and this enhancement by lithium was abolished by catecholamine depletion with reserpine or -methyl-p-tyrosine, but not by 5-HT depletion withp-chlorophenylalanine. These data suggest that lithium enhances 5-HT1A-mediated behavior via catecholaminergic systems. In contrast, chronic lithium treatment did not alter the hypothermic response to 8-OH-DPAT in untreated rats, as well as in rats treated with reserpine. These findings strengthen the suggestion that lithium has no direct influence on the postsynaptic 5-HT1A-mediated response. Other antimanic agents had no effect on either forepaw treading or hypothermia induced by 8-OH-DPAT. Radioligand binding studies using [3H]-8-OH-DPAT demonstrated that chronic lithium treatment, but not other antimanic agents, caused 5-HT1A receptor down-regulation in rat hippocampus. A discrepancy therefore exists between 5-HT1A receptor down-regulation and unaltered 5-HT1A-mediated behavioral and hypothermic responses in catecholamine-depleted rats after chronic lithium treatment. 相似文献
6.
López-Meraz ML González-Trujano ME Neri-Bazán L Hong E Rocha LL 《Neuropharmacology》2005,49(3):367-375
The effects of two serotonergic (5-HT1A) receptor agonists (8-OH-DPAT; 0.01, 0.1, 0.3, 1 mg/kg, s.c., and Indorenate; 1, 3, 10 mg/kg, i.p.) were evaluated in three type of seizures in male Wistar rats: clonic-tonic convulsions induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.), status epilepticus (SE) of limbic seizures produced by kainic acid (KA, 10 mg/kg, i.p.) and tonic-clonic seizures by amygdala kindling. 8-OH-DPAT decreased the incidence of tonic seizures and the mortality rate induced by PTZ. Indorenate increased the latency to the PTZ-induced seizures and decreased the percentage of rats showing tonic extension and death. Concerning KA, 8-OH-DPAT augmented the latency and reduced the frequency of wet-dog shake (WDS) and generalized seizure (GS). At high doses it diminished the occurrence and delayed the establishment of SE. Indorenate augmented the latency to WDS, GS and SE, and diminished the number of GS. 8-OH-DPAT and Indorenate did not alter the expression of kindled seizures. However, Indorenate enhanced the refractoriness to subsequent seizures during the postictal depression. Some effects induced by 8-OH-DPAT and Indorenate on seizures evaluated and postictal depression were fully or partially blocked by WAY100635. These results suggest that 5-HT1A receptor agonists modify epileptic activity depending on the type of seizure. 相似文献
7.
8.
J.-P. Voigt H. Fink C. A. Marsden 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(3):217-220
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 g/kg ip). In food deprived rats, CCK-8 (40 g/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. 相似文献
9.
T. Sharp R. McQuade S. Bramwell S. Hjorth 《Naunyn-Schmiedeberg's archives of pharmacology》1993,348(4):339-346
1. | Electrophysiological measurements of 5-HT neuronal activity report that repeated administration of 5-HT1A receptor agonists leads to desensitization of the 5-HT1A autoreceptor but this has not yet been detected in measurements of brain 5-HT synthesis or metabolism. Here we have determined the effect of repeated administration of 5-HT1A receptor agonists on brain 5-HT release using microdialysis. |
2. | Acute administration of the 5-HT1A receptor agonists buspirone (0.1–5 mg/kg s.c.) and ipsapirone (0.03–3 mg/kg s.c.) caused a dose-dependent decrease in 5-HT output in ventral hippocampus of the chloral hydrate anaesthetized rat. |
3. | The 5-HT response to buspirone (0.1 and 0.5 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was significantly inhibited by pre-treatment with the 5-HT1/-adrenoceptor antagonist pindolol (8–16 mg/kg s.c.). The 5-HT response to buspirone (0.1 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was not blocked by pretreatment with a combination of the 1 and 2-adrenoceptor antagonists metoprolol and ICI 118,551 (4 mg/kg s.c.). |
4. | The effect of an acute challenge of buspirone (0.5 mg/kg s.c.) on 5-HT output in ventral hippocampus was not attenuated in rats treated twice daily for 14 days with 0.5 or 5 mg/kg s.c. buspirone compared to saline-injected controls. Similarly, the decrease in 5-HT induced by an acute challenge of ipsapirone (0.5 mg/kg s.c.) was not attenuated in rats treated twice daily for 14 days with 5 mg/kg s.c. ipsapirone. |
5. | In further experiments it was shown that the decrease in 5-HT induced in both ventral hippocampus and striatum by an acute challenge of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.025 mg/kg s.c.), was not attenuated in rats treated twice daily for 14 days with 1 mg/kg s.c. 8-OH-DPAT. |
6. | Basal levels of 5-HT in hippocampal and striatal microdialysates of animals treated repeatedly with the 5-HT1A receptor agonists were not consistently altered relative to treatment controls. |
7. | In agreement with earlier studies measuring regional brain 5-HT synthesis and metabolism, the present microdialysis measurements of 5-HT release indicate that the inhibitory effect of 5-HT1A receptor agonists on presynaptic 5-HT function is maintained in rats treated repeatedly with the same drugs. |
10.
8-OH-DPAT, a selective 5-HT1A agonist, produced a hypothermic response in mice at a dosage of 0.5 mg/kg. Administration of corticosterone-21-acetate (0.5, 5 and 50 mg/kg, daily for 3 and 10 days) produced a dose-dependent attenuation of this hypothermic response in mice. When all controls and corticosterone treated mice were retested, 14 days after initial testing, they did not differ in the hypothermic responses induced by 8-OH-DPAT. Mice treated with aldosterone (50 mg/kg), dexamethasone (50 mg/kg) and the specific type 2 corticosteroid receptor agonist, 11b,17b-dihydroxy-21-methyl-17a-pregna-1,4,6-trien-20-yn-3-one (RU26988, 30 mg/kg) for 10 days, did not differ from vehicle treated controls in the hypothermic response to 8-OH-DPAT. Mice administered corticosterone-21-acetate (30 mg/kg, daily) for 10 days displayed a motor behavioural syndrome, which was not seen in controls, when injected with 5-hydroxytryptophan (5-HTP, 100 mg/kg) 15 min after the injection of carbidopa (25 mg/kg). This was significantly decreased by pretreatment with the 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)-piperazine (NAN-190 5 mg/kg, 30 min prior to administration of carbidopa). Taken together, this evidence is compatible with a specific corticosterone induced facilitation of 5-HT release due to attenuation of inhibitory 5-HT1A autoreceptor function. 相似文献
11.
Veenema AH Cremers TI Jongsma ME Steenbergen PJ de Boer SF Koolhaas JM 《Psychopharmacology》2005,178(2-3):151-160
Rationale Male wild house-mice genetically selected for long attack latency (LAL) and short attack latency (SAL) differ in structural and functional properties of postsynaptic serotonergic-1A (5-HT1A) receptors. These mouse lines also show divergent behavioral responses in the forced swimming test (FST, i.e., higher immobility by LAL versus SAL mice).Objectives We investigated whether the line difference in 5-HT1A receptors is associated with a difference in brain 5-HT metabolism, and whether acute administration of a 5-HT1A receptor agonist could differentially affect the behavioral responses of LAL and SAL mice.Methods 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in homogenates of several brain regions using high-performance liquid chromatography. The behavioral effect of the full 5-HT1A receptor agonist, 8-OH-DPAT, and of the somatodendritic 5-HT1A autoreceptor agonist, S-15535, was examined in the FST. The effect of 8-OH-DPAT on forced swimming-induced 5-HT metabolism in brain homogenates was determined.Results In most brain regions, 5-HT and 5-HIAA levels and 5-HT turnover were not significantly different between LAL and SAL mice. 8-OH-DPAT abolished the behavioral line difference in the FST by reducing immobility in LAL mice and reducing climbing in SAL mice. S-15535 induced a similar behavioral effect to 8-OH-DPAT in SAL mice, but did not alter the behavior of LAL mice. Compared with LAL, forced swimming elicited in SAL mice a higher brain 5-HT turnover, which was potently attenuated by 8-OH-DPAT.Conclusions It is unlikely that the difference in 5-HT1A properties between LAL and SAL mice is an adaptive compensatory reaction to changes in 5-HT metabolism. Although unspecific motor effects, at least in SAL mice, cannot be ruled out, it is suggested that the behavioral effects of 8-OH-DPAT and S-15535 may be mediated by predominant activation of postsynaptic 5-HT1A receptors in LAL mice and by presynaptic 5-HT1A receptors in SAL mice. 相似文献
12.
Guscott M Bristow LJ Hadingham K Rosahl TW Beer MS Stanton JA Bromidge F Owens AP Huscroft I Myers J Rupniak NM Patel S Whiting PJ Hutson PH Fone KC Biello SM Kulagowski JJ McAllister G 《Neuropharmacology》2005,48(4):492-502
The affinity of several antidepressant and antipsychotic drugs for the 5-HT7 receptor and its CNS distribution suggest potential in the treatment of psychiatric diseases. However, there is little direct evidence of receptor function in vivo to support this. We therefore evaluated 5-HT7 receptors as a potential drug target by generating and assessing a 5-HT7 receptor knockout mouse. No difference in assays sensitive to potential psychotic or anxiety states was observed between the 5-HT7 receptor knockout mice and wild type controls. However, in the Porsolt swim test, 5-HT7 receptor knockout mice showed a significant decrease in immobility compared to controls, a phenotype similar to antidepressant treated mice. Intriguingly, treatment of wild types with SB-258719, a selective 5-HT7 receptor antagonist, did not produce a significant decrease in immobility unless animals were tested in the dark (or active) cycle, rather than the light, adding to the body of evidence suggesting a circadian influence on receptor function. Extracellular recordings from hypothalamic slices showed that circadian rhythm phase shifts to 8-OH-DPAT are attenuated in the 5-HT7 receptor KO mice also indicating a role for the receptor in the regulation of circadian rhythms. These pharmacological and genetic knockout studies provide the first direct evidence that 5-HT7 receptor antagonists should be investigated for efficacy in the treatment of depression. 相似文献
13.
Brain serotonin 5-HT(1A) receptor, a traditional target for the treatment of mood disorders, modulates intracellular signalling pathways, such as the Extracellular signal-Regulated Kinases 1/2 (ERK1/2) pathway. The present studies are the first to determine levels of phospho-ERK1/2 (pERK1/2) in brain using a quantitative Enzyme Linked-Immuno-Sorbent Assay. We examined pERK1/2 levels in rat brain following administration of (+)8-OH-DPAT, buspirone as well as of the more selective, high-efficacy 5-HT(1A) agonists F13640 and F13714. Intraperitoneal injection of these compounds increased pERK1/2 in prefrontal cortex and hypothalamus, with a maximum at 5-15min and a significant effect lasting until 30-60min post-injection. However, these compounds reduced hippocampal pERK1/2 with a maximum effect at 30min, persisting until 60min post-injection. In hippocampus, F13640, F13714 and buspirone inhibited pERK1/2 in a dose-dependent manner as of 0.04, 0.04 and 2.5mg/kg, respectively. Given these low doses, this response is likely related to activation of sensitive presynaptic 5-HT(1A) receptors in the raphe nucleus. 4- and 16-fold higher doses of these compounds were necessary to stimulate pERK1/2 in prefrontal cortex and hypothalamus, respectively, via direct 5-HT(1A) receptor activation. In contrast, (+)8-OH-DPAT was active at similar doses (0.63mg/kg) in these different regions. Pretreatment with the 5-HT(1A) antagonist, WAY100635, completely blocked the effects of these compounds, with the exception of buspirone-induced pERK1/2 increases in hypothalamus. Thus, 5-HT(1A) agonist-induced changes in pERK1/2 in rat brain are time- and dose-dependent and region-specific. Furthermore, F13640, F13714, buspirone, but not (+)8-OH-DPAT, exert their effects via preferential activation of presynaptic 5-HT(1A) receptors. 相似文献
14.
J. E. Barrett S. M. Hoffmann S. N. Olmstead M. J. Foust C. Harrod B. A. Weissman 《Psychopharmacology》1989,97(3):319-325
The effects of spiroxatrine, a putative antagonist with selectivity for the serotonin (5-HT)1A receptor, were compared with compounds believed to function as agonists at the 5-HT1A receptor. Schedule-controlled responding of pigeons was maintained under a multiple 30-response fixed-ratio (FR), 3-min fixed-interval (FI) schedule or under a schedule in which responding was suppressed by electric shock (conflict procedure). Under the multiple schedule, spiroxatrine (0.3–1.0 mg/kg) decreased FR responding but did not affect FI responding; responding was decreased in both schedule components at 3.0 mg/kg. When administered alone, buspirone, a compound believed to produce its anxiolytic effects through 5-HT1A agonist actions, produced effects similar to those of spiroxatrine; in combination, the two drugs produced greater effects than when either was administered alone. As with 5-HT1A agonists such as buspirone and 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) in the pigeon, spiroxatrine (0.01–1.0 mg/kg) increased punished responding. Spiroxatrine and buspirone were potent inhibitors of [3H]8-OH-DPAT binding to pigeon cerebral membranes with IC50 values in the nM range. Neurochemical analyses of metabolite changes produced by spiroxatrine in pigeon cerebrospinal fluid showed buspirone-like effects, with increases in MHPG, DOPAC and HVA at doses that decreased 5-HIAA levels. Spiroxatrine dose-dependently blocked the behavioral effects of the dopamine agonist piribedil indicating that, like buspirone, it also is a potent dopamine antagonist. Spiroxatrine most likely functions as an agonist at the 5-HT1A receptor. As with buspirone, however, spiroxatrine has a prominent dopamine antagonist component. 相似文献
15.
Philippe Schoeffter Daniel Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(6):675-683
Summary The effects of several putative 5-HT1 receptorsubtype selective ligands were investigated in biochemical models for 5-HT1A, 5-HT1B, and 5-HT1D receptors (inhibition of forskolin-stimulated adenylate cyclase activity in calf hippocampus, rat and calf substantia nigra, respectively) and 5-HT1C receptors (stimulation of inositol phosphates production in pig choroid plexus). Following compounds were studied: 5-HT (5-hydroxytryptamine), TFMPP (1-(mtrifluoromethylphenyl)piperazine), mCPP (1-m-chlorophe-nyl)piperazine, 1 CGS 12066 (7-trifluoromethyl-4-(4-methyl1-piperazinyl)-pyrrolo[1,2-a]quinoxaline 1), isamoltane (CGP 361A, 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propranol), quipazine, 1-NP (1-(1-naphthyl)piperazine), and PAPP (LY165163, 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine). Among reported 5-HT1B receptor selective drugs, TFMPP had similar potency at 5HT1A, 5-HT1B and 5-HT1C receptors, mCPP did not separate between 5-HT1B and 5-HT1C receptors, CGS 12066 was equipotent at 5-HT1B and 5-HT1D receptors, and isamoltane was only slightly 5-HTIB versus 5-HT1A selective. Quipazine showed equal potency at 5-HTIB and 5-HT1C receptors and 1-NP did not discriminate between the four receptor subtypes. PAPP described as 5-HT1A receptor selective, was equally potent at 5-HT1A and 5-HT1D receptors. The potencies determined in second messenger studies were in good agreement with the affinity values determined in radioligand binding studies. Thus 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors have different pharmacological profiles as predicted from radioligand binding studies. Despite claims to the contrary, none of the tested compounds had actual selectivity for a given 5-HT1 receptor subtype. Of interest were the properties of several of these drugs, which behaved as agonists at some receptors and as antagonists at others (e. g. quipazine, 1-NP, PAPP and isamoltane).
Send offprint requests to D. Hoyer at the above address 相似文献
16.
Centenaro LA Vieira K Zimmermann N Miczek KA Lucion AB de Almeida RM 《Psychopharmacology》2008,201(2):237-248
Rationale Social instigation is used in rodents to induce high levels of aggression, a pattern of behavior with certain parallels to
that of violent individuals. This procedure consists of a brief exposure to a provocative stimulus male, before direct confrontation
with an intruder. Studies using 5-HT1A and 5-HT1B receptor agonists show an effective reduction in aggressive behavior. An important site of action for these drugs is the
ventral orbitofrontal cortex (VO PFC), an area of the brain which is particularly relevant in the inhibitory control of aggressive
and impulsive behavior.
Objectives The objectives of the study are to assess the anti-aggressive effects of 5-HT1A and 5-HT1B agonist receptors [8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) and CP-93,129] in the VO PFC of socially provoked male mice. To confirm the
specificity of the receptor, 5-HT1A and 5-HT1B antagonist receptors (WAY-100,635 and SB-224,289) were microinjected into the same area, in order to reverse the agonist
effects.
Results 8-OH-DPAT (0.56 and 1.0 μg) reduced the frequency of attack bites. The lowest dose of CP-93,129 (0.1 μg) also decreased the
number of attack bites and lateral threats. 5-HT1A and 5-HT1B receptor agonists differed in their effects on non-aggressive
activities, the former decreasing rearing and grooming, and the latter, increasing these acts. Specific participation of the
1A and 1B receptors was verified by reversal of anti-aggressive effects using selective antagonists WAY-100,635 (10.0 μg)
and SB-224,289 (1.0 μg).
Conclusions The decrease in aggressiveness observed with microinjections of 5-HT1A and 5-HT1B receptor agonists into the VO PFC of socially provoked mice, supports the hypothesis that activation of these receptors modulates
high levels of aggression in a behaviorally specific manner. 相似文献
17.
Rationale Tryptophan depletion is used to reduce central serotonergic function and to investigate its role in psychiatric illness. Despite
widespread clinical use, its effects on serotonin (5-HT) receptors have not been well characterized.
Objective The aim of this study was to examine the effect of acute (ATD) and chronic tryptophan depletion (CTD) on free-plasma tryptophan
(TRP), central TRP and 5-HT and brain 5-HT1A and 5-HT2A receptor binding in the rat.
Methods TRP and 5-HT were measured by high-performance liquid chromatography and receptor levels determined by homogenate radioligand
binding and in-vitro receptor autoradiography.
Results Free-plasma TRP, central TRP and central 5-HT levels were significantly and similarly reduced by ATD and 1- and 3-week CTD
compared to controls. ATD significantly reduced 5-HT1A binding in the dorsal raphe (14%) but did not significantly alter postsynaptic 5-HT1A binding (frontal cortex, remaining cortex and hippocampus) or 5-HT2A binding (cortex and striatum). One-week CTD did not significantly alter cortical 5-HT2A binding or postsynaptic 5-HT1A binding. Furthermore, 3-week CTD did not significantly alter 5-HT1A binding but significantly increased cortical 5-HT2A binding without affecting striatal or hippocampal levels. In the CTD 1 and 3-week groups, rat body weight was significantly
decreased as compared to controls. However, weight loss was not a confounding factor for decreased cortical 5-HT2A-receptor binding.
Conclusion ATD-induced reduction in somatodendritic 5-HT1A autoreceptor binding may represent an intrinsic ‘homeostatic response’ reducing serotonergic feedback in dorsal raphe projection
areas. In contrast, the increase in 5-HT2A receptor after CTD may be a compensatory response to a long-term reduction in 5-HT. 相似文献
18.
Jakub Staroń Ryszard Bugno Adam S. Hogendorf Andrzej J. Bojarski 《Expert opinion on therapeutic patents》2018,28(9):679-689
Introduction: 5-HT1AR was one of the first discovered serotonin receptors and is one of the most thoroughly studied. Dysfunctions associated with 5-HT1AR neurotransmission are linked to several psychiatric disorders, including anxiety, depression, and movement disorders.
Areas covered: The current review covers patent literature published between January 2012 and May 2018. Queries were performed on Espacenet, SciFinder, clinicaltrials.gov, pharmacodia.com, and the websites of pharmaceutical companies.
Expert opinion: Several novel therapeutic applications have been proposed for 5-HT1AR ligands, i.e. prostate cancer treatment, gastrointestinal and cardiopulmonary disorders, facilitation of urination and defecation, and L-DOPA-induced dyskinesia. Interestingly, no patent application has been filed by big pharma companies, while numerous researches are being conducted in smaller companies and academia. 相似文献
19.
Circadian rhythm in the behavioral responsiveness to the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied in rats. Rats were subcutaneously injected with 8-OH-DPAT at one of the following times of day: 0000, 0400, 0800, 1200, 1600, 2000 hours. The postsynaptic 5-HT1A receptor behavioral syndrome, that is, forepaw treading, head weaving, and flat body posture, were measured after the administration of 8-OH-DPAT. Circadian rhythms were found in each of the behavioral responses to 8-OH-DPAT. Peak responses were observed in the mid-dark phase (1200 hours) while the weakest responses were observed in the midlight phase (0000 hours). In a subsequent experiment, 8-OH-DPAT was administered intracerebroventricularly during the mid-dark phase and the mid-light phase. The behavioral responses to the drug in the middark phase were significantly higher than those in the mid-light phase. These results suggest that the function of central postsynaptic 5-HT1A receptor exhibits circadian rhythm. 相似文献
20.
F. Chaouloff V. Baudrie D. Laude 《Naunyn-Schmiedeberg's archives of pharmacology》1990,341(4):381-384
Summary 8-Hydroxy-2-(di-n-propylamino)tetralin (8OH-DPAT) is a 5-HT1A receptor-selective agonist that has recently been reported to trigger adrenal catecholamine release and hyperglycemia. The aim of this study was to analyze in the conscious rat whether the 5-HT1A receptor subtype is involved in these effects.8-OH-DPAT (0.1–1 mg/kg, i.v.) evoked dose-dependent increases in plasma adrenaline and glucose concentrations. Increases in plasma adrenaline levels peaked 5 min after administration of 8-OH-DPAT; in contrast, plasma glucose levels rose throughout the 20 min period of analysis. Prior administration of (–)pindolol, a beta-adrenoceptor antagonist that blocks 5-HT1A receptors, markedly diminished the rise in plasma adrenaline levels and abolished the hyperglycemia triggered by 8-OHD-PAT. On the other hand, neither the selective beta 1-adrenoceptor antagonist, betaxolol, the selective beta 2-adrenoceptor antagonist, ICI 118.551, nor the 5-HT2 receptor antagonist, ketanserin, affected 8-OH-DPAT-induced increases in plasma adrenaline levels. In addition, except for ICI 118.551 pretreatment, which delayed the hyperglycemic effect of 8-OH-DPAT, none of these antagonists affected the rise in glycaemia evoked by 8-OHD-PAT.The data suggest that the adrenaline-releasing and a major part of the hyperglycemic effects of 8-OH-DPAT are mediated by activation of 5-HT1A receptors.
Send offprint requests to F. Chaouloff at the above address 相似文献