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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 examined the short- and long-term effects of single and repeated administration of 3,4-methylenedioxy-methamphetamine (MDMA, 'ecstasy') on somatodendritic and postsynaptic 5-HT1A receptors of the rat brain. [3H]8-Hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) was used to label 5-HT1A receptors in the brain stem region containing the dorsal raphe nucleus and in the frontal cortex. As expected, both schedules of treatment reduced the serotonin (5-hydroxytryptamine, 5-HT) content and [3H]paroxetine binding in the frontal cortex but not in the brain stem. Multiple but not single MDMA administration significantly reduced 5-HT1A receptor density in the selected brain stem region. In the frontal cortex, both MDMA treatments increased or tended to increase 5-HT1A receptor number, the effect being more marked after repeated drug administration.
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PMID:Methylenedioxymethamphetamine induces opposite changes in central pre- and postsynaptic 5-HT1A receptors in rats. 856 8

8-Hydroxy(di-n-propylamino)tetralin (8-OH-DPAT; 0.1-50 mg/kg i.p.) evoked a dose-dependent mydriatic response in conscious mice (ED50 = 5.8 mg/kg i.p.) which was maximal after 10 min. 8-OH-DPAT (2 mg/kg i.p.)-induced mydriasis was attenuated by the alpha 2-adrenoceptor antagonists, idazoxan (1 and 3 mg/kg i.p.) and yohimbine (1 and 3 mg/kg i.p.), by the 5-HT1 receptor antagonists, pindolol (10 mg/kg i.p.) and quipazine (2 mg/kg i.p.), and by the selective 5-HT1A receptor antagonist, (-)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenyl propionamide ((-)-WAY 100135; 1-10 mg/kg s.c.). These data argue that both central alpha 2-adrenoceptors and 5-HT1A receptors are involved in the mediation of mydriasis induced by 8-OH-DPAT. The synaptic location of these receptors was determined using either N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 100 mg/kg i.p.) or 5,7-dihydroxytryptamine (5,7-DHT; 75 micrograms i.c.v.)+p-chlorophenylalanine (PCPA; 200 mg/kg i.p.); these lesioning procedures respectively produced highly significant losses of whole brain noradrenaline (72% depletion) and 5-HT (78% depletion). The former abolished 8-OH-DPAT (5 mg/kg i.p. (ED50)) mydriasis, whereas the latter was without effect. 8-OH-DPAT (0.5-5 mg/kg i.p.) also dose-dependently increased the noradrenaline metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG), in mouse whole brain minus cerebellum. Taken together these results show that 8-OH-DPAT initially stimulates 5-HT1A receptors, and it is likely that this is followed by release of noradrenaline onto postsynaptic alpha 2-adrenoceptors, the latter effect being responsible for the mydriatic response.
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PMID:8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation. 898 15

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced temperature reduction, lower lip retraction and tail flick responses are widely used models of 5-HT1A receptor function. To obtain information about the sites of receptors mediating these effects we measured these responses, parallel over wide dose ranges after intracerebroventricular (i.c.v., 0.6-67 micrograms/kg) and intravenous (i.v., 3-500 micrograms/kg) administration. Analysis of the dose-response curves provided evidence for a 9.8-fold ratio of the potency of 8-OH-DPAT following i.c.v. compared to i.v. administration on body temperature reduction (ED50 values are 5.1 and 50 micrograms/kg, after i.c.v and i.v. administration, respectively) and a 2.9-fold ratio in potency for lower lip retraction (ED50 values are 29 and 86 micrograms/kg, after i.c.v. and i.v. administration, respectively). 8-OH-DPAT was less potent in the induction of tail flicks than of the other responses and had a lower potency after i.c.v. than after i.v. administration (ED50 values, the first one extrapolated, are 526 and 246 micrograms/kg, after i.c.v. and i.v. administration, respectively). In addition, the i.c.v. ED50 for temperature reduction was significantly lower than those for lower lip retraction or tail flick responses. The relative potency, that is, the ratio of i.v. and i.c.v. ED50, was significantly higher for temperature reduction than for lower lip retraction or tail flick responses (ED50 i.v./ED50 i.c.v. values are 9.8, 2.9, and 0.47, respectively). These data provide evidence that distinct sites of action are involved in these models. Temperature reduction is mediated mainly by postsynaptic receptors in the close vicinity of the lateral ventricle. Receptors that mediate lower lip retraction are located more distantly in the brain, supporting previous evidence that they are somatodendritic autoreceptors, and receptors in the spinal cord are probably responsible for tail flick responses.
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PMID:Comparison of relative potencies of i.v. and i.c.v. administered 8-OH-DPAT gives evidence of different sites of action for hypothermia, lower lip retraction and tail flicks. 910 76

The spontaneously hypertensive (SHR) and Lewis (LEW) strains differ in numerous behavioral tests, including the elevated plus-maze. In keeping with the crucial role of central serotonin (5-HT) in anxiety, we checked for strain differences regarding several determinants of 5-HT activity. In addition to confirming that LEW rats displayed anxious behaviors in the plus-maze compared with SHR, we found that in vitro, central tryptophan hydroxylase activity was higher in LEW rats than in SHR. However, ex vivo studies in midbrains and hippocampi revealed that neither 5-HT synthesis nor 5-HT and 5-hydroxyindoleacetic acid levels differed between strains. [3H]8-Hydroxy-2-(di-n-pro-pylamino)tetralin binding at midbrain 5-HT1A autoreceptors and hippocampal 5-HT1A postsynaptic receptors, [3H]ketanserin binding at cortical and striatal 5-HT2A receptors and [3H]citalopram binding at midbrain and hippocampal 5-HT transporters did not vary between strains. The inhibition of 5-HT synthesis by 5-HT1A autoreceptor stimulation was similar in both strains. Forepaw treading and flat body posture after 5-HT1A postsynaptic receptor stimulation were higher and lower, respectively, in SHR than in LEW rats. Last, 1-(4-iodo-2,5-dimethoxy-phenyl)-2-aminopropane- and quipazine-elicited head shakes, a 5-HT2A receptor-mediated response, were increased in the SHR strain compared with the LEW strain; on the other hand, 1-(3-chlorophenyl)piperazine triggered similar 5-HT2B/2C receptor-mediated decreases in motor activity in the two strains. This study shows that although the low-anxiety (SHR) and high-anxiety (LEW) strains vary in some aspects of 5-HT function, key components such as the 5-HT1A autoreceptors are not different.
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PMID:Central serotonergic systems in the spontaneously hypertensive and Lewis rat strains that differ in the elevated plus-maze test of anxiety. 915 85

The effects of ionophoretically applied 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists were studied on rat nucleus tractus solitarius (NTS) neurones receiving unmyelinated vagal afferent input. 5-HT excited 15 of 34 neurones (44%), inhibited 10 (29%) and had no effect on nine. 8-Hydroxy-2-(di-N-propylamino)tetralin HBr (8-OH-DPAT) excited 23 of 53 neurones (43%), inhibited 24 (45%) and had no effect on six neurones and (+/-)-2,5-dimethoxy-4-iodoamphetamine HCl activated 18 of 37 neurones (49%), inhibited nine (24%) and had no effect on 10. These results demonstrate that activation of 5-HT1A and 5-HT2 receptors can excite or inhibit populations of NTS neurones. Phenylbiguanide, however, excited 20 of 23 neurones (87%), inhibited only one (4%) and had no effect on two indicating that 5-HT3 receptor activation has an excitatory action. NTS neurones receiving cardiac vagal afferent input were more likely to be excited by 5-HT (five of five, 100%) or 8-OH-DPAT (four of five. 80%) than the population as a whole. In conclusion, the data demonstrate that 5-HT1A, 5-HT2, and 5-HT3 receptor subtypes are functionally present on NTS neurones receiving excitatory vagal afferent input. Further, the subpopulation of NTS neurones receiving input from cardiac afferents are excited by 5-HT, possibly by an action on 5-HT1A or 5-HT3 receptors.
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PMID:In vivo effects of 5-hydroxytryptamine receptor activation on rat nucleus tractus solitarius neurones excited by vagal C-fibre afferents. 922 74

(+/-)-8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), (+)-8-OH-DPAT, and (-)-8-OH-DPAT produced dose-related reversals of haloperidol-induced extrapyramidal side effects (EPS) in cebus monkeys, with all compounds producing similar almost complete reversals at 0.1 mg/kg i.m. These compounds were more potent than apomorphine, which reversed haloperidol-induced EPS at 0.3, but not 0.1, mg/kg i.m. The data indicate that the reversal of haloperidol-induced EPS by (+/-)-8-OH-DPAT and its enantiomers is mediated via effects at 5-HT1A receptors, not dopamine D2 receptors. Thus, inclusion of 5-HT1A agonist activity in novel antipsychotics may reduce EPS liability.
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PMID:Reversal of haloperidol-induced extrapyramidal side effects in cebus monkeys by 8-hydroxy-2-(di-n-propylamino)tetralin and its enantiomers. 953 54

The present study was undertaken to identify the receptor subtypes involved in (+/-) pindolol's ability to enhance the effects of antidepressant drugs in the mouse forced swimming test. Interaction studies were performed with S 15535 (presynaptic 5-HT1A receptor agonist) and methiothepin (5-HT1B autoreceptor antagonist) in an attempt to attenuate or potentiate antidepressant-like activity. (+/-) Pindolol was tested in combination with selective agonists and antagonists at 5-HT1, 5-HT2 and 5-HT3 receptor subtypes. Pretreatment with S 15535 and methiothepin attenuated the activity of paroxetine, fluvoxamine and citalopram (32 mg/kg, i.p.; P < 0.01). (+/-) Pindolol (32 mg/kg, i.p.) induced significant anti-immobility effects when tested in combination with 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.; P < 0.05), 1-(2-methoxyphenyl)-4-[-(2-phthalimido) butyl]piperazine) (NAN 190) (0.5 mg/kg; P < 0.05) and ondansetron (0.00001 mg/kg, i.p.; P < 0.01). Pretreatment with NAN 190 (0.5 mg/kg, i.p.) potentiated the effects of RU 24969 (1 mg/kg, i.p.; P < 0.05) and (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) in the forced swimming test, as did ondansetron (0.00001 mg/kg, i.p.). Significant additive effects were induced when RU 24969 (1 mg/kg, i.p.) was tested in combination with NAN 190 (0.5 mg/kg, i.p.; P < 0.05), (+/-) pindolol (32 mg/kg, i.p.; P < 0.05) and ondansetron (0.0000 mg/kg, i.p.; P < 0.05). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.) did not induce significant antidepressant-like effects with any of the agonists/antagonists tested. The results of the present study suggest that pindolol is acting at presynaptic 5-HT1B serotonergic receptors, in addition to the 5-HT1A subtype, in augmenting the activity of antidepressants in the mouse forced swimming test.
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PMID:Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test. 956 7

The present study was designed to examine the neurochemical effects of (+/-)-mirtazapine (10 mg kg(-1) i.p.) and its enantiomers in rats. Male Sprague-Dawley rats received either (+)-mirtazapine, (-)-mirtazapine, (+/-)-mirtazapine or vehicle, by intraperitoneal injection for two weeks. Maximum change in temperature from baseline, following a single dose of the 5-HT1A receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.15 mg kg(-1) s.c.), was used to assess the function of the 5-HT1A receptors. Chronic drug treatment potentiated this response, with (+/-)-mirtazapine > (-)-mirtazapine > (+)-mirtazapine. Receptor changes were also observed with a slight decrease in beta1-adrenoceptor density, although this failed to reach significance. A significant decrease in beta1-adrenoceptor affinity was observed following (-)-mirtazapine treatment. All drugs tested significantly reduced the density of the 5-HT2 receptors. Results of the present study suggest that in so far as alterations in these receptor populations are important for the therapeutic action of antidepressants, neither of the enantiomers appear to be more active than the racemic mixture.
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PMID:Neurochemical effects of the enantiomers of mirtazapine in normal rats. 977 41

8-Hydroxy-2-[di-n-propylamino]-tetralin) (8-OH-DPAT), a 5-HT1A/7 receptor agonist, has a chronobiological effect on the circadian system. To identify how the 8-OH-DPAT exerts this effect, we specifically destroyed the serotonergic (5-HT) fibres connecting the median raphe nuclei (RN) to the suprachiasmatic nuclei (SCN) of the hypothalamus by using microinjections of a neurotoxin 5,7-dihydroxytryptamine into the SCN. After administration of 8-OH-DPAT (0.1 ml, 5 mg/kg) at circadian time 7, the control and the 'partially-lesioned' animals showed a large phase-advance whereas in the 'well-lesioned' hamsters the phase-advances were significantly reduced or absent. The present study demonstrates that, in the Syrian hamster, the 5-HT fibres connecting the RN to the SCN are essential for the phase-shifting action of peripheral 8-OH-DPAT injections, and that the drug does very probably not exert its chronobiological effect directly onto SCN neurons but through receptors localized on median raphe nucleus neurons.
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PMID:In Syrian hamsters, 5-HT fibres within the suprachiasmatic nuclei are necessary for the expression of 8-OH-DPAT induced phase-advance of locomotor activity rhythm. 983 10

The ionic channels and signal transduction pathways underlying the 5-hydroxytryptamine (5-HT)-induced hyperpolarization in neurons of the rat dorsolateral septal nucleus (DLSN) were examined by using intracellular and voltage-clamp recording techniques. Application of 5-HT (1-50 microM) caused a hyperpolarizing response associated with a decreased membrane resistance in DLSN neurons. The hyperpolarization induced by 5-HT was blocked by Ba2+ (1 mM) but not by tetraethylammonium (TEA, 3 mM), glibenclamide (100 microM) and extracellular Cs+ (2 mM). 8-Hydroxy-di-n-propylamino tetralin (8-OH-DPAT; 3 microM), a selective agonist for the 5-HT1A receptor, mimicked 5-HT in producing the hyperpolarization. The 5-HT hyperpolarization was blocked by NAN-190 (5 microM), a 5-HT1A receptor antagonist. CP93129 (100 microM), a 5-HT1B receptor agonist, and L-694-247 (100 microM), a 5-HT1B/1D receptor agonist, also produced hyperpolarizing responses. The order of agonist potency was 8-OH-DPAT >> CP93129 > or = L-694-247. (+/-)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride (DOI, 100 microM), a 5-HT2 receptor agonist, and RS67333 (100 microM), a 5-HT4 receptor agonist, caused no hyperpolarizing response. The voltage-clamp study showed that 5-HT caused an outward current (I5-HT) in a concentration-dependent manner. I5-HT was associated with an increased membrane conductance. I5-HT reversed the polarity at the equilibrium potential for K+ calculated by the Nernst equation. I5-HT showed inward rectification at membrane potentials more negative than-70 mV. Ba2+ (100 microM) blocked the inward rectifier K+ current induced by 5-HT. I5-HT was irreversibly depressed by intracellular application of guanosine 5'-O-(3-thiotriphosphate)(GTP-gamma S) but not by guanosine 5'-O-(2-thiodiphosphate) (GDP beta S). These results suggest that in rat DLSN neurons activation of 5-HT1A receptors causes a hyperpolarizing response by activating mainly the inward rectifier K+ channels through a GTP-binding protein.
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PMID:Effects of 5-hydroxytryptamine on neuronal activities in the rat dorsolateral septal nucleus. 991 16


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