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 effects of postmortem delay, time of storage, and freezing, thawing, and refreezing tissue samples were studied in postmortem rat brain using conditions that reflect the handling of postmortem human brain before neurochemical analysis. The levels of monoamines and metabolites in the striatum and cingulate and occipital cortex were measured using alumina extraction and HPLC methods. Binding of raclopride to dopamine D2, SCH-23390 to dopamine D1, ketanserin to serotonin 5-HT2, 8-hydroxy-2-(di-n-propylamino)tetralin to serotonin 5-HT1A, and cholecystokinin (CCK)-8 to CCK-B sites was measured in tissue homogenates from the striatum or fronto-parietal cortex. An 18-h postmortem delay before dissection and storage resulted in region-specific changes in monoamine and metabolite levels. Binding to striatal D1 and frontoparietal cortex CCK-B sites was reduced over the course of a 27-h postmortem delay. Binding to D2 and 5-HT sites was relatively stable. Storage of tissue for up to 8 months also resulted in region-specific changes in monoamine and metabolite levels. No changes in receptor binding were seen after long-term storage. Freezing, thawing, and refreezing tissue samples resulted in increased levels of striatal 3,4-dihydroxyphenylacetic acid and decreased binding to striatal D2 sites. These results demonstrate time-, temperature-, and storage-dependent regional differences in the stability of monoamines and their metabolites and in binding to various receptor sites. These differences in stability and binding should be accounted for to interpret accurately the effects of neurological disorders on neurotransmitter dynamics in postmortem human brain tissue.
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PMID:Postmortem stability of monoamines, their metabolites, and receptor binding in rat brain regions. 750 13

Dopamine D2-like receptor labeled by [3H]YM-09151-2 in the rat hippocampus proper was examined by in vitro receptor autoradiography. In the dorsal hippocampus, [3H]YM-09151-2 bindings were high in the whole layers of CA1, the stratum pyramidale of CA4 and the stratum molecular of gyrus dentatus, moderate in the stratum oriens of CA3 and hilus of the gyrus dentatus, and low in remaining CA3 and the subiculum. In the ventral hippocampus, the binding densities were high in the stratum oriens and the stratum radiatum of CA1, the stratum pyramidale of CA4, and the stratum moleculare of gyrus dentatus, moderate in the stratum lacnosum moleculare of CA1 and the hilus of the gyrus dentatus. Saturation analysis using hippocampal sections demonstrated that the Kd value was about five times higher than that using striatal sections. The rank order potency of competition on [3H]YM-09151-2 binding by dopaminergic ligands in the hippocampus was YM-09151-2 > (+)-butaclamol > dopamine > sulpiride > SCH-23390; which shows the appropriate dopamine D2-like receptor profile. The hippocampal [3H]YM-09151-2 binding did not represent serotonergic receptors (5-HT1A and 5-HT2) and sigma receptor, since Ki values of ketanserine, serotonin, 8-OH-DPAT and DTG were much lower than D2-like receptor antagonists. These findings suggest tha [3H]YM-09151-2 binds hippocampal D2-like receptor site with different association kinetics of striatal D2-like receptor site, and demonstrates widespread distribution of D2-like receptor in the hippocampus with distinct region-specific profile.
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PMID:Dopamine D2-like receptors labeled by [3H]YM-09151-2 in the rat hippocampus: characterization and autoradiographic distribution. 755 74

The present study assessed compounds displaying affinity for 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors for their ability to substitute for, enhance or antagonize the discriminative stimulus effects of cocaine (10 mg/kg) in rats. In substitution tests, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT; 0.2-1.6 mg/kg), the 5-HT1A/B receptor agonists RU 24969 (0.25-2 mg/kg) and CGS 12066B (2-16 mg/kg), the 5-HT1B/2C receptor agonists m-chlorophenylpiperazine (mCPP; 0.25-2 mg/kg) and m-trifluoromethylphenylpiperazine (TFMPP; 0.125-2 mg/kg), the 5-HT2A/2C receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane ([+/-]-DOB; 0.0625-0.5 mg/kg), the 5-HT2C receptor agonist MK 212 (0.25-1 mg/kg) and the nonselective 5-HT receptor agonist quipazine (1-8 mg/kg) engendered 30% to 70% cocaine-appropriate responding. The DA receptor antagonists SCH 23390 (0.025 or 0.05 mg/kg) and haloperidol (0.125 or 0.25 mg/kg) failed to block the partial substitution of RU 24969 (1 mg/kg) for cocaine. In combination tests, a fixed dose of either quipazine (4 mg/kg), RU 24969 (0.25, 0.5 or 1 mg/kg) or TFMPP (0.5 mg/kg) but not 8-OH-DPAT (0.4 mg/kg) or CGS 12066B (16 mg/kg) produced a leftward shift in the cocaine dose-response curve (0.625-5 mg/kg). In contrast, coadministration of either mCPP (0.25-2 mg/kg) or MK 212 (0.125-2 mg/kg) plus a dose of cocaine (5 mg/kg) that produced > 85% cocaine-appropriate responding when given alone partially antagonized cocaine; mCPP (1 mg/kg) also produced a rightward shift in the cocaine dose-response curve. Neither 8-OH-DPAT (0.2-1.6 mg/kg), (+/-)-DOB (0.125-0.5 mg/kg) nor quipazine (2-8 mg/kg) blocked the cocaine stimulus. The 5-HT1A receptor antagonist NAN 190 (0.2-0.8 mg/kg), the 5-HT2A/2C receptor antagonist LY 53857 (0.5-4 mg/kg) and the 5-HT/DA receptor antagonist pirenperone (0.5-4 mg/kg) neither substituted for nor enhanced cocaine; however, pirenperone but not NAN 190 or LY 53857 partially blocked the cocaine (10 mg/kg) response. Although 5-HT receptor compounds do not substitute for cocaine, several 5-HT receptor agonists (i.e., the indole derivative RU 24969 and the arylpiperazines mCPP, MK 212, TFMPP and quipazine), but not antagonists, differentially modulate the stimulus effects of cocaine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulation of the discriminative stimulus properties of cocaine by 5-HT1B and 5-HT2C receptors. 756 16

The possible control by monoamines of the spinal release of substance P- and calcitonin gene-related peptide-like materials (SPLM and CGRPLM, respectively) was investigated in vitro, using slices of the dorsal half of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Whereas the spontaneous outflow of SPLM and CGRPLM was changed by none of the agonists/antagonists of monoamine receptors tested, the overflow of both peptide-like materials due to 30 mM K+ was differentially affected by alpha 2-adrenoreceptor and dopamine D-1 receptor ligands. Noradrenaline (10 microM to 0.1 mM) and clonidine (0.1 mM) significantly reduced the K(+)-evoked overflow of SPLM, and both effects could be prevented by idazoxan (10 microM) and prazosin (10 microM) as expected from their mediation through the stimulation of alpha 2B-adrenoreceptors. In contrast, CGRPLM overflow remained unaffected by alpha 2-adrenoreceptor ligands. Dopamine D-1 receptor stimulation by SKF 82958 (10-100 nM) significantly increased the K(+)-evoked overflow of both SPLM and CGRPLM, and this effect could be prevented by the selective D-1 antagonist SCH 39166 (1 microM). Further studies with selective ligands of other monoamine receptors indicated that neither alpha 1- and beta-adrenergic receptors, dopamine D-2, nor serotonin 5-HT1A and 5-HT3 receptors are apparently involved in some control of the spinal release of CGRPLM and SPLM. These data are discussed in line with the postulated presynaptic control by monoamines of primary afferent fibres conveying nociceptive messages within the dorsal horn of the spinal cord.
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PMID:Monoaminergic control of the release of calcitonin gene-related peptide- and substance P-like materials from rat spinal cord slices. 768 7

In this study, the involvement of serotonergic and dopaminergic receptors in the modulation of the head-twitch (HTW) response to the 5-hydroxytryptamine (5-HT)2A/5-HT2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, was characterized in rats using novel and selective ligands at 5-HT2A, 5-HT2C, D1, D2 and 5-HT1A receptors. HTW were dose-dependently inhibited by the 5-HT2A/2C antagonists, ritanserin, metergoline, mesulergine, mianserin, ICI 169,369 and LY 58,537, by the preferential 5-HT2A antagonist, ketanserin and by the novel, selective 5-HT2A antagonist, SR 46349B. A further selective 5-HT2A antagonist, MDL 100,907, very potently abolished HTW (ED50 = 0.005 mg/kg). The order of relative potency correlated highly with their affinity at 5-HT2A (r = 0.83) but not 5-HT2C receptors (r = 0.06). In addition, the novel, selective 5-HT2C antagonist, SB 200,646A, failed to abolish HTW and the 5-HT2C agonists/5-HT2A antagonists, 1-(3-chlorophenyl)piperazine and 1-(3-trifluoromethylphenyl)piperazine, blocked, rather than elicited, HTW. The D1 antagonists, SCH 23390, NNC 112, NNC 756, SCH 39166 and A 69024, in this order of relative potency that correlated with their affinity at D1 receptors (r = 0.98), blocked HTW. The D2 antagonists, raclopride, eticlopride and haloperidol also blocked HTW. The 5-HT1A agonists, S 14671, S 14506, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, ipsapirone and (+)-flesinoxan, abolished HTW. The action of 8-hydroxy-2-(di-n-propylamino)tetralin was blocked by (-)-tertatolol (ID50 = 4.5 mg/kg), a novel 5-HT1A receptor antagonist. Similarly, (-)-tertatolol attenuated the action of S 14506 and abolished that of S 14671, buspirone and ipsapirone. A role of postsynaptic 5-HT1A receptors in the action of 5-HT1A agonists was suggested by the finding that parachlorophenylalanine (3 x 300 mg/kg, i.p.), which depleted cerebral pools of 5-HT, did not modify the activity of ipsapirone. The present data demonstrate that 5-HT2A receptors mediate HTW in rats and that both D1 and D2 receptors as well as (postsynaptic) 5-HT1A receptors play a role in their expression.
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PMID:(1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists. 771 55

The biochemical changes in DA and 5HT systems were investigated in amphetamine (AMPH)-sensitized rats, 1 and 15 days after cessation of treatment (5 mg/kg AMPH, i.p., twice a day for 6 days). At both times, AMPH-treated rats exhibited behavioral sensitization, as revealed by an enhancement of the stereotypic response to a challenge dose of 2 mg/Kg, ip. AMPH. Basal dopamine (DA) and serotonin (5-HT) metabolism was not significantly modified in different brain areas of AMPH-sensitized rats. Quantitative autoradiographic analysis of DA and serotonin 5-HT receptor subtypes was performed in the following brain regions: medial prefrontal cortex, nucleus accumbens, striatum, substantia nigra, ventral tegmental area, dorsal and median raphe nuclei. A significant increase of [3H]SCH 23390 binding to D1 DA receptors was observed in the substantia nigra pars reticulata 1 day but not 15 days after the cessation of AMPH treatment, whereas [3H]8-OH-DPAT binding to 5-HT1A sites was found to be significantly enhanced in the dorsal raphe nucleus at both time points. No change in D2 DA nor in 5-HT1B or 5-HT2A receptors was found in any of the brain structures examined at either time point. The obtained results suggest that DA and 5-HT systems are differently and time-dependently involved in AMPH-induced behavioral sensitization.
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PMID:Short and long-term changes in dopamine and serotonin receptor binding sites in amphetamine-sensitized rats: a quantitative autoradiographic study. 779 32

The role of serotonergic (5-HT) receptor subtypes in mediation of aggressive behaviour in isolated male mice has been studied. Increase of attack latency was used as a simple measure of antiaggressive behaviour. 5-HT1A agonists (BAY R 1531, 8-OHDPAT, flesinoxan, gepirone, 5MeO DMT, buspirone, ipsapirone, BMY 14802) completely inhibit the aggressive behaviour irrespective of their intrinsic activities. Also the putative antagonists spiroxatrine and NAN 190 as well as the non-selective 5-HT1 agonists RU 24969, TFMPP, mCPP and eltoprazine have an antiaggressive effect. The mixed 5-HT1A and beta-adrenoceptor antagonists (-)-alprenolol and pindolol are ineffective and do not inhibit the effect of 8-OHDPAT. Neither does the non-selective 5-HT antagonist metergoline. The antiaggressive effect correlates with 5-HT1A receptor affinity in vitro and with generalization to the 8-OHDPAT-induced discriminative stimulus. The selective 5-HT uptake inhibitor citalopram does not inhibit aggressive behaviour. The 5-HT2 agonist DOI has an antiaggressive effect only at high doses, whereas the 5-HT2 antagonist ritanserin and the 5-HT3 antagonist ondansetron are ineffective. Prazosin (alpha 1-adrenoceptor antagonist), clonidine (alpha 2-adrenoceptor agonist), clenbuterol (beta-adrenoceptor agonist), ketanserin (5-HT2 receptor and alpha 1-adrenoceptor antagonist), clozapine and (-)-octoclothepin (dopamine (DA), 5-HT2 receptor and alpha 1-adrenoceptor antagonist) all show an antiaggressive effect. SCH 23390 (DA D1 receptor antagonist) and emonapride (DA D2 receptor antagonist) are ineffective. In conclusion, 5-HT1A receptors are involved in mediation of isolation-induced aggressive behaviour in mice. The involvement of other 5-HT receptor subtypes needs further clarification. The adrenergic system may also be involved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice. 787 Aug 99

In the present study a cross-familiarisation conditioned taste aversion (CTA) paradigm was utilized to reveal stimulus resemblance between the selective 5-HT1A agonist 8-OHDPAT and a variety of serotonergic and non-serotonergic drugs. In male mice, a 0.22 mg/kg dose of 8-OHDPAT was used as the reference compound inducing CTA. Dose-dependent effects of pre-exposure to 24 different test drugs on the magnitude of the 8-OHDPAT-induced CTA were tested as a measure for stimulus similarity between these test drugs and 8-OH-DPAT (the reference compound). Pre-exposure to 8-OH-DPAT itself, ipsapirone, buspirone, RU 24969, sertraline, d-amphetamine, LSD, metergoline and idazoxan effectively prevented the development of CTA induced by 8-OHDPAT. Pre-exposure to apomorphine, diazepam, SCH 23390, LiCl, spiperone, DOI, spiroxatrine, umespirone, pindolol, mCPP, haloperidol, MK 212, clonidine, quipazine and also 5-MeODMT was not effective in completely abolishing the CTA produced by 8-OHDPAT. It is concluded from these results that the relatively simple and fast cross-familiarisation taste aversion method is a suitable paradigm to study similarities in stimulus properties of different drugs.
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PMID:Cross-familiarisation conditioned taste aversion procedure as a method to reveal stimulus resemblance between drugs: studies on the 5-HT1A agonist 8-OHDPAT. 787 Oct

The present study was designed to evaluate the roles of serotonin 5-HT1A and 5-HT2 receptors in the effects of neuroleptic drugs in the paw test. This behavioural test has been shown to model both the antipsychotic efficacy as well as the extrapyramidal side-effect liability of neuroleptic drugs. Whereas the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) reduced the effects of the classical neuroleptic haloperidol, it increased the effects of the atypical neuroleptic clozapine. The 5-HT2 receptor antagonist ketanserin as well as the 5-HT1C/5-HT2 receptor antagonist ritanserin, on the other hand reduced the effects of haloperidol, whereas the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) reduced the effects of clozapine. The most important finding, however, was that the behavioural effects of different (putative) neuroleptics (fluphenazine, SCH-39166, remoxipride, prothipendyl, thioridazine and risperidone) were differentially influenced by both 8-OHDPAT and DOI, suggesting that there are important differences between the neuronal mechanisms underlying the behavioural effects of these neuroleptic drugs, even within the subclasses of classical and atypical neuroleptics.
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PMID:The role of serotonin receptor subtypes in the behavioural effects of neuroleptic drugs. A paw test study in rats. 790 18

Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.
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PMID:Antagonism by SCH 23390 of clozapine-induced hypothermia in the rat. 791 99


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