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)

Auditory evoked middle latency responses recorded in the hippocampus (HAER), were monitored in alert, gently restrained rats with chronic indwelling electrodes and cannulae. Intrahippocampal (i.h.) injection of 5-hydroxytryptamine (5-HT, 10 micrograms) reduced the amplitude and increased the latency of the N28 and P55 peaks of the HAER. An early (P18) negative peak was unaffected. Buspirone (1 microgram, i.h. and 3 mg/kg, i.p.) had similar effects to those produced by i.h. 5-HT. RU 24969 (1 mg/kg, s.c.) also reduced the amplitude of the N28 peak of the HAER. Long-term treatment with buspirone for 14 days at a dose (0.5 mg/kg, i.p.) which when applied acutely did not produce any observable effect, caused an increase in the latency of both the N28 and P55 peaks. Direct i.h. injection of 5-HT into these chronically treated animals did not have any additional depressant effect on the HAER peaks. It is concluded that these serotoninergic agonists can modulate the later peaks of the HAER possibly via 5-HT1A receptors. In the case of buspirone there was evidence of an enhanced depressant effect following chronic treatment [corrected].
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PMID:Serotoninergic depression of auditory evoked responses recorded in the rat hippocampus: effect of repeated buspirone treatment. 150 59

Rats were treated by intraperitoneal injection for four weeks with either RU24969, a 5-HT1B and 5-HT1A agonist or imipramine, a 5-HT uptake inhibitor. Pre- and postsynaptic 5-HT receptors were measured to compare the effect of direct or indirect stimulation of the 5-HT autoreceptor (5-HT1B receptor). The 5-HT transport protein (5-HT uptake site), labelled with [3H]paroxetine, was unaffected after treatment with either one of the drugs. The density of 5-HT2 receptors, labelled with [3H]ketanserin, we found increased after treatment with RU24969 (Bmax = 161 fmol/mg protein) and decreased after treatment with imipramine (Bmax = 109 fmol/mg protein) as compared with control rats (Bmax = 134 fmol/mg protein). The 5-HT1B receptor was found decreased both by the imipramine treatment (Bmax = 106 fmol/mg protein) and the treatment with RU24969 (Bmax = 105 fmol/mg protein), compared with control rats (Bmax = 130 fmol/mg protein). The 5-HT1A receptor was found to be decreased after treatment with RU24969 (control: Bmax = 62 fmol/mg protein; RU24969-treated: 49 fmol/mg protein), but unchanged after treatment with imipramine (Bmax = 58 fmol/mg protein). These results correspond to what could be expected, if the 5-HT1B receptor is the 5-HT autoreceptor.
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PMID:Serotonin receptors in the brain of rats treated chronically with imipramine or RU24969: support for the 5-HT1B receptor being a 5-HT autoreceptor. 150 39

The effects of serotonin (5-HT) were investigated by intracellular recording from 179 dorsal root ganglion (DRG) cells classified by conduction velocity. Bath applied 5-HT depolarized 82% and hyperpolarized 4% of the A-type cells. In C-type cells, 5-HT depolarized only 41%, but hyperpolarized 39% of the cells. The depolarizing responses were of two types; an increase or decrease in R(in), mediated by 5-HT2or3 receptors, respectively. These receptors were observed in both A- and C-type cells. Hyperpolarizing responses were largely confined to A(delta)- and C-type cells. Carboxamidotryptamine and 8-OH-dipropylamino-tetralin were full agonists in eliciting hyperpolarization, and metitepin, spiperone and spiroxitrine behaved as competitive antagonists. This indicated that hyperpolarization was mediated by a 5-HT1A receptor. A 5-HT1A&3 receptor were found co-localized on some C-type cells. A strong depolarizing response to capsaicin was observed in the subgroup of C-type neurons that were also hyperpolarized by 5-HT. Thus a co-localization of capsaicin and 5-HT1A receptors was also observed.
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PMID:Serotonin preferentially hyperpolarizes capsaicin-sensitive C type sensory neurons by activating 5-HT1A receptors. 151 4

Anabolic steroids and other androgens, such as testosterone propionate (TP), have a facilitatory role in the expression of aggressive behavior. Based upon literature indicating an inverse relationship between aggression and the central neurotransmitter serotonin (5-HT), the present study was undertaken to investigate the role of 5-HT in androgen-induced aggression. In this study, an animal model of aggression involving competition between male rat pairs for sugar pellets was used to investigate the effects of TP. When TP was administered daily (30 mg/kg) to nondominant rats, these animals became dominant. Dominant behavior was found to be stable throughout the study with continued daily administration of TP. To test the serotonergic component of TP-induced aggression, the serotonergic agonist 2-(1-piperazinyl) quinolone dimaleate (quipazine) was administered acutely to TP-dominant rats. Quipazine dose dependently reduced aggressive dominance in TP-dominant rats, as well as in naturally dominant rats. When the serotonergic antagonists pirenpirone or pizotyline were coadministered with quipazine to either group of dominant rats, they blocked the effect of quipazine in reducing dominance. However, when 1-[1H-Indol-4-yloxy]-3-[isopropylamino]-2-propanol (pindolol), a drug that acts at both beta-adrenergic receptors and at 5-HT1A and 5-HT1B receptors, was coadministered with quipazine there was a reversal of the quipazine effect on aggression only in TP-dominant rats. These results indicate that androgen-induced aggression may involve a complex alteration in serotonergic neurotransmission.
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PMID:Reversal of testosterone-induced dominance by the serotonergic agonist quipazine. 151 63

Various models of rodent agonistic behaviour are described, which differentiate between offensive and defensive/flight models. Particular attention is given to one male and one female paradigm for offensive aggression, viz. resident-intruder or territorial (RI) and maternal aggression (MA). After an overview of the serotonin (5-HT) system in the CNS, a description is given of the ligands available. Subsequently the effects of various drugs affecting serotonergic transmission in the RI- and MA-paradigms are described. The 5-HT1A agonists buspirone, ipsapirone and 8-OH-DPAT decreased aggression in RI and MA, but simultaneously led to a marked decrease in social interest and activity, indicative of a non-specific anti-aggressive profile. Non-selective 5-HT1 agonists, such as RU 24969, eltoprazine (DU 28853), and TFMPP reduced aggression quite specific and did not decrease social interest or exploration, but sometimes even increased these behaviours. In RI and MA the behavioural effects of these drugs were roughly similar. In contrast, MA was more sensitive to the treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression only non-specifically at the highest dose. DOI, a 5-HT2 and 5-HT1C agonist, decreased aggressive behaviour and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by 'wet dog shaking', characteristic of 5-HT2-receptor stimulation. The non-specific 5-HT agonist (and 5-HT3 antagonist) quipazine also induced 'wet dog shaking' at doses which suppressed aggression, social interest and exploration but increased inactive behaviours (sitting and lying). The discussion attempts to delineate a role for 5-HT receptor subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs stressing the consistent role of 5-HT in different forms of aggression.
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PMID:Rodent models of aggressive behavior and serotonergic drugs. 151 29

Repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of the 5-HT1A partial agonist, buspirone, or placebo. The difference in rCBF, before and after drug, (buspirone versus placebo) was used to identify brain areas affected by buspirone. Buspirone-induced changes in rCBF were studied under two behavioural conditions (5 word-list learning and 15 word-list learning). Compared to placebo, buspirone increased blood flow in the cuneus during both behavioural states. However, decreases in blood flow, centred in the left dorso-lateral prefrontal cortex and posterior cingulate cortex, were only observed under one of the two behavioural conditions. It is concluded that buspirone-induced alterations in regional cerebral blood flow are better understood, not in relation to the known distribution of monoamine neurotransmitter systems (particularly ascending 5-HT projections), but rather in relation to putative neuronal circuits possibly many synapses "downstream" of buspirone's pharmacological site of action.
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PMID:Effect of the 5-HT1A partial agonist buspirone on regional cerebral blood flow in man. 152 87

5-Hydroxytryptamine (5-HT) was injected into the rostral ventrolateral medulla (RVLM) in urethane-anaesthetized rats and its effect assessed on thermoregulatory and non-thermoregulatory cutaneous circulations by the measurement of skin surface temperatures. 5-Hydroxytryptamine (5-50 nmol) produced a dose-related fall in blood pressure (5-20 mmHg) and an increase in tail and plantar foot surface temperatures, indicative of dilatation in the underlying cutaneous circulations. If heat was not applied to the animal, the body temperature fell by 1-2 degrees C within 15-25 min. The decrease in tail and foot temperatures, produced by low frequency (25 Hz, 5 min) electrical stimulation, was antagonized by the injection of 5-HT at the site of stimulation. 5-Carboxyamidotryptamine (2.5-20 nmol) and flesinoxan (5-25 nmol) produced responses similar to 5-HT. The 5-HT2 receptor agonist, alpha-methyl 5-hydroxytryptamine (alpha-methyl 5-HT, 5.5-100 nmol) was only effective in increasing tail and plantar foot temperatures, at dose levels above 25 nmol. However, in a few sites restricted to the anterior region of the RVLM, alpha-methyl 5-HT (11 nmol) evoked a small decrease in tail and foot temperatures, indicative of a constrictor effect, without influencing resting cardiovascular parameters. The results are discussed in relation to the central mechanisms which underly the hypothermia and hyperthermia produced by 5-HT1A and 5-HT2 receptor agonists.
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PMID:Changes in the tail surface temperature of the rat following injection of 5-hydroxytryptamine into the ventrolateral medulla. 152 3

The purported serotonin (5-HT)1A antagonists BMY-7378 and NAN-190 were examined in pigeons for their potential to block the effects of the prototypical 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on punished ("conflict") and unpunished behavior and for their binding affinity at the 5-HT1A receptor site labeled by [3H]-8-OH-DPAT. Although BMY-7378 and NAN-190 both displayed high affinity for the 5-HT1A receptor (IC50 values of 0.8 and 7.5 nM, respectively), their effects, when administered alone, as well as in combination with 8-OH-DPAT, were distinct. 8-OH-DPAT (0.3-3.0 mg/kg) produced large increases in punished responding at doses that did not affect or that decreased unpunished responding. Administration of NAN-190 (1.0-3.0 mg/kg) did not increase punished responding, whereas BMY-7378 (1.0-5.6 mg/kg) slightly increased behavior suppressed by punishment. Pretreatment with BMY-7378 attenuated the rate-increasing effects of 8-OH-DPAT on punished responding; however, these effects were accompanied by dose-dependent enhancement of the rate-decreasing effects of 8-OH-DPAT on unpunished responding. In contrast, NAN-190 blocked the rate-increasing effects of 8-OH-DPAT on punished responding and also reversed the rate-decreasing effects of 8-OH-DPAT on responding that was not punished. Pretreatment with NAN-190 failed to block increases in punished responding produced by 0.1 to 1.0 mg/kg of the benzodiazepine midazolam. These data suggest that NAN-190 may be characterized as an antagonist and BMY-7378 a partial agonist with respect to 5-HT1A-induced behavioral changes observed in the conflict procedure with pigeons.
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PMID:Antagonism studies with BMY-7378 and NAN-190: effects on 8-hydroxy-2-(di-n-propylamino)tetralin-induced increases in punished responding of pigeons. 153 59

The effect of systemic administration of the 5-HT precursor, 5-hydroxy-L-tryptophan (5-HTP) on the release of 5-HT in the lateral hypothalamus of the chloral hydrate-anaesthetized rat in vivo was examined using brain microdialysis. Administration of 5-HTP caused an immediate increase of 5-HT in dialysates, which was long lasting (greater than or equal to 140 min) and dose-dependent (30-100 mg/kg i.p.). When calcium was omitted from the perfusion medium, thereby limiting exocytosis, levels of basal 5-HT were significantly decreased and the 5-HTP-induced response of 5-HT was markedly attenuated. Administration of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (0.25 mg/kg i.p.), which selectively inhibits serotoninergic neuronal activity by activation of the somatodendritic 5-HT autoreceptor, significantly decreased basal levels of 5-HT and markedly attenuated the 5-HTP-induced increase in 5-HT. The data demonstrate that systemic administration of 5-HTP caused an increase in the release of 5-HT in the hypothalamus. Furthermore, this release occurred by a calcium-dependent mechanism (probably exocytosis), was dependent on serotoninergic neuronal activity and predominantly derived from 5-HT neurones. The findings are discussed in relation to the behavioral and neuroendocrine effects of increasing availability of the 5-HT precursor.
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PMID:Effect of 5-hydroxy-L-tryptophan on the release of 5-HT in rat hypothalamus in vivo as measured by microdialysis. 153 65

This study was designed to determine the subtypes of 5-HT receptors present in bovine large coronary arteries and to characterize the response mediated by each subtype of receptor. Concentration-response relationships for 8-hydroxy-2-(di-n-propylamino)-tetralin (5-HT1A agonist) (0.3-100 microM), CGS-12066B maleate (5-HT1B agonist) (0.01-30 microM), alpha-methylserotonin maleate (5-HT2 agonist) (0.01-30 microM), 1-(m-chlorophenyl)-biguanide (5-HT3 agonist) (0.1-100 microM) and serotonin (0.1-300 microM) were studied in vitro using 2-mm segments of bovine proximal left anterior descending coronary artery. Each segmental ring was mounted in a 70-ml tissue bath for the measurement of isometric tension. 8-Hydroxy-2-(di-n-propylamino)-tetralin (10-100 microM), alpha-methylserotonin maleate (0.01-30 microM) and serotonin (0.1-300 microM) induced endothelium-independent contraction, whereas CGS-12066B maleate and 1-(m-chlorophenyl)-biguanide had no effect in this species. Contractions induced by 8-hydroxy-2-(di-n-propylamino)-tetralin or alpha-methylserotonin maleate were attenuated by pretreatment with S(-)propranolol (2.6 microM), a relatively selective 5-HT1A and 5-HT1B receptor antagonist, and ketanserin (0.3 microM), a selective 5-HT2 receptor antagonist, respectively. Pretreatment with S(-)propranolol or ketanserin also attenuated serotonin-induced contraction, demonstrating that serotonin mediates contraction through both 5-HT1A and 5-HT2 receptors in bovine large coronary arteries.
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PMID:Characterization of 5-hydroxytryptamine receptors in bovine coronary arteries. 153 67


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