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 striatum contains a high concentration of oxidizable dopamine (DA), and the aged organism shows a decreased ability to respond to oxidative stress (OS), making this area extremely vulnerable to free radical insult. To determine the receptor specificity of this putative increase in OS sensitivity, striatal slices from 6- and 24-month-old animals were incubated (30 min, 37 degrees C) in a modified Krebs medium containing 0 to 500 microM DA with or without a preincubation (15 min) in a nitrone trapping agent, 1 or 5 mM alpha-phenyl-n-tert-butyl nitrone (PBN), and changes in low Km GTPase activity (an index of receptor-G protein coupling/uncoupling) assessed in muscarinic, 5-HT1A D1, and D2 receptors stimulated with carbachol, 8 OH-DPAT-HBr, SKF 38393, or quinelorane, respectively. DA exposure induced selective decreases in the stimulated activity in all of these receptor systems, and an overall increase in conjugated dienes (56%) of the young. In the case of carbachol and 8 OH-DPAT-HBr, the DA-induced deficits in GTPase stimulation were seen primarily in the young (61 and 32%, respectively), while DA-induced deficits in quinelorane (D2) stimulation were seen in both age groups. In the case of SKF 38393-stimulation (D1) the DA-induced deficits were higher in the striatal tissue from the old. The DA-induced decreases in carbachol stimulated GTPase activity in the tissue from the young could be prevented by pretreatment with PBN or the DA uptake inhibitor, nomifensin. No effect of nomifensin was seen in the old, because their DA uptake mechanisms were already compromised. These results suggest that although age-related declines in DA uptake may provide some protection against the OS effects in muscarinic or 5-HT1A receptors, other factors may increase the vulnerability of DA neurons to OS, even with reductions in DA uptake.
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PMID:Receptor- and age-selective effects of dopamine oxidation on receptor-G protein interactions in the striatum. 958 13

Regularly cycling, proestrous female rats received infusions of 200 ng of the serotonin (5-HT) 1A receptor agonist, (+/-) 8-hydroxy 2-(di-n-propylamino) tetralin-HBr (8-OH-DPAT), or 200 ng 8-OH-DPAT and 1000 or 2000 ng of N-(3-trifluoro-methylphenyl) piperazine hydrochloride (TFMPP) or 2-(1-piperazinyl) quinoline dimaleate (quipazine). Infusions were made bilaterally into the ventromedial nucleus of the hypothalamus (VMN). Animals receiving 200 ng 8-OH-DPAT exhibited a decline in lordosis behavior following infusion. Rats receiving 8-OH-DPAT and 1000 or 2000 ng quipazine or TFMPP were protected from the lordosis-inhibiting effects of 8-OH-DPAT, alone. Although both quipazine and TFMPP act on multiple 5-HT receptors, they overlap in their agonist action at 5-HT2 receptors. Consequently, these results provide further evidence supporting the contention that within the VMN, both 5-HT1A and 5-HT2 receptor subtypes contribute to the modulation of lordosis behavior in the female rat. The data are discussed in terms of the relative potency of 5-HT at 5-HT receptors mediating inhibition and facilitation of lordosis behavior.
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PMID:Attenuation of the lordosis-inhibiting effects of 8-OH-DPAT by TFMPP and quipazine. 975 39

Ligands with varying intrinsic activity and selectivity for the various subtypes of the serotonin receptor were tested in the rat pup ultrasonic vocalization (USV) model, a putative animal model reflecting anxiety. USV were elicited by isolating rat pups from their mother and littermates by placing them on a warm (37 degrees C) or a cold (18 degrees C) plate. Concurrently, the negative geotaxic (NG) response and rectal temperature were determined to assess the potentially sedative and hypothermic effects of putative anxiolytics. USV were reduced at low doses and in both temperature conditions by the full 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin.HBr) and the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378 (2-[4-[4-[2-pyrimidinyl]-1,2-piperazinyl]butyl]-1,2-benzi-isoth iozol-3-(2H)one-1,1-dioxide. 2HCl). The 5-HT1A receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalimido)-butyl]piperazide.2H Cl), (+/-)-WAY 100,135 (+/-)-(N-tert-butyl-3(4-(2-methoxy phenyl)piperazin-1 -yl)-2-phenyl propionamine.2HCl), and ((S)-UH-301 (S)-5-fluoro-8-hydroxy-2-(di-n-propyl-amino)tetralin.HBr) reduced USV at higher doses and only in one of both test conditions. The selective 5-HT1A receptor antagonist DU 125530 (2-[4-[4[(7-chloro-2,3dihydro-4-benzodioxin-5-yl)-1-piperazi nyl]butyl]-1,2-benzisothiazol-3(2H)-one-1,1, dioxide, monomesylate), did not influence USV at the cold plate up to high doses, although concomitantly the negative geotaxis was disturbed. The negative geotaxis was impaired after all 5-HT1A receptor ligands, except BMY 7378 and (+/-)-WAY 100,135. Hypothermia coincided with USV-suppression, except for NAN-190 and (S)-UH-301. The USV-suppressing action of flesinoxan (3 mg/kg) could be antagonized by DU 125530, but not its NG effect. However, the hypothermia induced by flesinoxan was antagonized by DU 125530. USV were also suppressed by the 5-HT uptake inhibitors fluvoxamine (both warm and cold plate) and clomipramine (only warm plate). The tricyclic antidepressant imipramine only decreased USV on the cold plate, however, in a U-shaped dose-response curve. At the highest dose tested, no decrease was present. The 5-HT uptake stimulant tianeptine reduced USV under both conditions. Fluvoxamine had no side effects, clomipramine induced hypothermia and tianeptine clearly had sedative properties. The 5-HT1B/2C receptor agonist TFMPP (trifluorometaphenylpiperazine) stimulated USV at a low dose at the cold plate and suppressed USV at a high dose under both conditions. The 5-HT2A/2C receptor antagonist ketanserine enhanced USV at low doses under both conditions and had no effect at a higher dose. Concurrently heavy sedation and hypothermia occurred. The 5-HT3 receptor agonist phenylbiguanide and the 5-HT3 receptor antagonist ondansetron had no effect in this paradigm. Clearly, subtypes of the 5-HT receptor affect rat pup USV differentially.
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PMID:Ultrasonic vocalizations in rat pups: effects of serotonergic ligands. 988 14

Activation of serotonin (5-hydroxytryptamine, 5-HT) receptors in the brain produces cardiovascular responses by altering autonomic outflow. The paraventricular nucleus (PVN) contains a modest density of 5-HT receptors and has connections to autonomic centers. Experiments were designed to determine whether cardiovascular responses were produced by the administration of 5-HT2- and 5-HT1A-receptor agonists into the PVN of conscious rats. The microinjection of the 5-HT2-receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] into the PVN produced dose-dependent (1-10 nmol) increases in heart rate and blood pressure; the peak responses were +39 +/- 10 beats/min and +6 +/- 2 mm Hg, respectively. Both responses were blocked by the concomitant administration of the selective 5-HT2-receptor antagonist LY53857 into the PVN. By contrast, the microinjection of the selective 5-HT1A-receptor agonist R(+)-8-OH-DPAT [R(+)8-hydroxy-2-(di-n-propylamino) tetralin HBr; 1-10 nmol] into the PVN did not affect blood pressure or heart rate. These data suggest that 5-HT neurons projecting from the raphe nuclei to or near the PVN can participate in the central control of the cardiovascular system by way of 5-HT2 receptors. Apparently 5-HT neurons terminating in the PVN can increase blood pressure and heart rate and produce sympathoadrenal activation, metabolic and hormonal responses consistent with those observed in several different stress paradigms.
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PMID:Cardiovascular responses produced by microinjection of serotonin-receptor agonists into the paraventricular nucleus in conscious rats. 1002 23

5-HT(1B/D) receptor agonists such as GR46611 (3-[3-(2-Dimethylaminoethyl)-H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide ) are known to lower body temperature in guinea pigs. Although stimulation of their functional analogs in rats, the 5-HT1B receptor induces hyperlocomotion, this effect has yet to be demonstrated with 5-HT(1B/D) receptor agonists in the guinea pig. Previous studies have shown that 5-HT1A agonists increase locomotor activity in guinea pigs. The current study set out to examine the effects of 5-HT(1B/D) receptor stimulation on locomotor activity in the guinea pig and to examine the interaction between 5-HT1A and 5-HT(1B/D) receptor stimulation on locomotor activity in that species. The full agonist at 5-HT1A receptors, 8-OH-DPAT (R(+)-8-Hydroxy-dipropylaminotetralin HBr) dose-dependently increased locomotor activity in guinea pigs (0.3-1.25 mg kg(-1) s.c.), as to a lesser extent, did the partial agonist, buspirone (8-[4-[4-(2-Pyramidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5 ]decane-7,9-dione HCl) (5.0-20.0 mg kg(-1) s.c.). The 5-HT(1B/D) receptor agonist GR46611 had no effect on locomotor activity in guinea pigs at doses up to 40 mg kg(-1) s.c. 8-OH-DPAT-induced behavioural activation was reversed by the selective 5-HT1A receptor antagonist WAY100635 (N-[-2-[4-(-methoxyphenyl)-1-piperazinyl]ethyl]-N-(pyrinidyl) cyclo hexanocarboxamide trihydro-chloride), with a minimum effective dose of 0.006 mg kg(-1), but not by the 5-HT(1B/D) receptor antagonist GR127935 (2'-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxyli c acid [4-methoxy-3-(4-methyl-piperazin-1-yl)phenyl]-amide) (0.25-1.0 mg kg(-1)). GR46611, at doses that were without effect given alone (0.5-2.5 mg kg(-1)), significantly enhanced the locomotor response to subthreshold doses of 8-OH-DPAT (0.5 mg kg(-1)) and buspirone (10 mg kg(-1)). The effect of GR46611 on 8-OH-DPAT-induced hyperactivity was reversed by pretreatment with GR127935 and with WAY 100635 indicating that activation of both receptors was required for the expression of locomotor hyperactivity. These findings suggest that activation of 5-HT(1B/D) receptors alone may not stimulate locomotor activity but it does potentiate the locomotion induced by 5-HT1A receptor stimulation in guinea pigs.
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PMID:GR46611 potentiates 5-HT1A receptor-mediated locomotor activity in the guinea pig. 1032 55

The conditioned taste aversion procedure in mice was used to test for blockade of the drug stimulus of the 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT), 1-(4-trifluoromethyl-2-pyridinyl)-4- [4-[2-oxo-1-pyrrolidinyl]butyl]piperazine (E)-2-butenedioate (Org 13011) and the 5-HT reuptake inhibitor fluoxetine. The conditioned taste aversion induced by 8-OH-DPAT (0.22 mg/kg) and Org 13011 (0.5 mg/kg) was readily blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) (0.1 mg/kg). The conditioned taste aversion induced by fluoxetine could not be antagonized by WAY-100635 nor by the 5-HT2 receptor antagonist mianserin. It is concluded that the conditioned taste aversion induced by 8-OH-DPAT or Org 13011 is mediated via 5-HT1A receptors. The results suggest that the conditioned taste aversion induced by fluoxetine is not exclusively mediated by 5-HT1A receptors nor exclusively by 5-HT2 receptors. The results also indicate that the conditioned taste aversion paradigm can be used to test for antagonism of stimulus properties of compounds.
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PMID:Antagonism of the 5-HT1A receptor stimulus in a conditioned taste aversion procedure. 1042 96

The objective of this study was to examine possible interactions between serotonergic and dopaminergic agents lowering core temperature via stimulation of 5-HT1A and dopamine (DA) D2 receptors, respectively. The effects of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) and the DA D2/3 receptor agonist 7-OH-DPAT on core temperature was monitored in adult male Wistar rats, approximately 300 g body weight. The temperature probe was connected to a PC-assisted temperature instrument, and an automated printer device was activated when the temperature reading had stabilized (+/-0.1 degrees C) for 10 s. As expected, 7-OH-DPAT [0.5 and 2.0 micromol x kg(-1) subcutaneous (s.c.)] as well as 8-OH-DPAT (0.15-2.4 micromol x kg(-1) s.c.), produced a dose-dependent hypothermia. When combined, there were additive effects of the two compounds, although the effects of 7-OH-DPAT were attenuated by 8-OH-DPAT at the higher doses (0.6-2.4 micromol x kg(-1)), in all probability because of emerging DA D2 receptor blocking properties of the latter compound.
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PMID:Additive hypothermic effects of the 5-HT1A receptor agonist 8-OH-DPAT and the dopamine D2/3 receptor agonist 7-OH-DPAT in the rat. 1147 7

(1) The study was aimed to investigate the effects of the minimal effective doses of acute citalopram (5 mg/kg), (+/-)-8-hydroxydipropylaminotetralin HBr (8-OH-DPAT; 0.1 mg/kg), and their combined treatment on the rat open field and forced swimming behaviour and post-mortem monoamine content. (2) The animals were prospectively divided into the vehicle- and para-chlorophenylalanine (p-CPA)-pretreated (350 mg/kg) groups. (3) Acute citalopram (5 mg/kg), 8-OH-DPAT (0.1 mg/kg), or their combined treatment had no major effect on the rat open field and forced swimming behaviour. (4) The post-mortem catecholamine content in four brain regions studied was unchanged in all treatment groups. (5) The combined 8-OH-DPAT (0.1 mg/kg) and citalopram (5 mg/kg) treatment partially reversed the p-CPA-induced decrease of serotonin (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) content. (6) The present experiments demonstrate that the 5-HT1A receptors mediate some of the selective serotonin reuptake inhibitor (SSRI)-induced biochemical phenomena.
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PMID:Role of 5-HT1A receptors in the mediation of acute citalopram effects: a 8-OH-DPAT challenge study. 1181 98


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