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)

Our findings show that administration of the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino] tetralin) was able to induce significant phase-advances 4 h before onset of hamster locomotor activity under constant darkness. All other non-photic treatments applied such as melatonin, dimethyl sulphoxide, Ringer, saline or enforced wheel-running failed to induce any significant phase-advances. Similar results were obtained in pinealectomized animals. In constant light (LL), all treatments produced phase-advances. These results show that: (1) LL seems to be an inappropriate constant condition to study the chronobiological effect of drugs or other non-photic stimuli; (2) the endogenous circadian pacemaker (SCN) can be affected specifically by 8-OH-DPAT.
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PMID:Effects of the 5-HT1a receptor agonist 8-OH-DPAT and other non-photic stimuli on the circadian rhythm of wheel-running activity in hamsters under different constant conditions. 808 32

In humans, 5-HT1A receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT1A receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT1A receptor expression in the living human brain was assessed using the 5-HT1A-selective positron emission tomography (PET) ligand [11C]WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT1A receptor gene, the influence of the common SNP [(-1018) C>G] on 5-HT1A receptor expression was examined in a group of 35 healthy individuals scanned with [11C]WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT1A receptor density. Whereas, the 5-HT1A receptor genotype did not show any significant effects on [11C]WAY 100635 binding, 5-HT1A receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT1A receptor gene, affects 5-HT1A receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states.
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PMID:A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. 1575 68

Nonphotic phase-shifting of mammalian circadian rhythms is thought to be mediated in part by serotonin (5-HT) acting in the suprachiasmatic nucleus (SCN) circadian clock. Previously we showed that brief (1-3 days) exposure to constant light (LL) greatly potentiates nonphotic phase-shifting induced by the 5-HT agonist, (+/-)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT). Here we investigated potential mechanisms for this action of LL, including 5-HT receptor upregulation and SCN clock gene and neuropeptide gene expression. Autoradiographic analysis of ritanserin inhibition of [3H]8-OH-DPAT binding indicated that LL (approximately 2 days) did not affect 5-HT7 receptor binding in the SCN or dorsal raphe. Measurement of 5-HT1A autoreceptors in the median raphe and 5-HT1B receptors in the SCN also showed no effect of LL. In experiment 2, hamsters held under a 14-h light : 10-h dark photocycle (LD) or exposed to LL for approximately 2 days received an intraperitoneal injection of 8-OH-DPAT or vehicle at zeitgeber time (ZT) 6 or 0 and were killed after 2 h of dark exposure. 8-OH-DPAT suppressed SCN Per1 and Per2 mRNAs at both ZTs, as assessed by in situ hybridization. Per1 mRNA was also suppressed by LL alone. In addition, in situ hybridization of arginine vasopressin (AVP) mRNA and vasoactive intestinal polypeptide mRNA showed that LL significantly suppressed the former but not the latter. The LL-induced suppression of SCN Per1 mRNA and AVP mRNA may be involved in LL-induced potentiation of pacemaker resetting, especially as these data provide additional evidence that LL suppresses circadian pacemaker amplitude, thus rendering the clock more susceptible to phase-shifting stimuli.
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PMID:Short-term constant light potentiation of large-magnitude circadian phase shifts induced by 8-OH-DPAT: effects on serotonin receptors and gene expression in the hamster suprachiasmatic nucleus. 1626 68

Short-term (1-3 days) constant light exposure (brief LL) potentiates nonphotic phase shifting induced by sleep deprivation and serotonin (5-HT) agonist stimulation. The present assessments reveal that exposure to brief LL markedly alters the magnitude and shape of the 5-HT1A,7 receptor agonist, 8-(+)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahyronapthalene (8-OH-DPAT) phase-response curve, facilitating (approximately 12 h) phase-advance shifts during the early morning when serotonergics have no phase-shifting effect. Brief LL also reduces the threshold for 8-OH-DPAT shifting at midday, evidenced by 5- to 6-h phase-advance shifts elicited by dosages that have no effect without the LL treatment. The brief LL-potentiated phase advances to intraperitoneal 8-OH-DPAT at zeitgeber time 0 (ZT 0) were blocked by the 5-HT1A antagonists, pindolol and WAY 100635, indicating that this shifting is mediated by 5-HT1A receptors. Antagonists with action at 5-HT7 receptors, including ritanserin and metergoline, were without effect. Although autoradiographic analyses of [3H]8-OH-DPAT binding indicate that brief LL does not upregulate suprachiasmatic nucleus (SCN) 5-HT1A receptor binding, intra-SCN microinjection of 8-OH-DPAT at ZT 0 in brief LL-exposed hamsters induced shifts similar to those produced by intraperitoneal injection, suggesting that SCN 5-HT1A receptors mediate potentiated 8-OH-DPAT-induced shifts during the early morning. Lack of shifting by intra-SCN 8-OH-DPAT at ZT 6 or 18 (when intraperitoneal 8-OH-DPAT induces large shifts), further indicates that brief LL-potentiated shifts at these time points are mediated by 5-HT target(s) outside the SCN. Significantly, sleep deprivation-induced phase-advance shifts potentiated by brief LL (approximately 9 h) at ZT 0 were blocked by pindolol, suggesting that these behavioral shifts could be mediated by the same SCN 5-HT1A receptor phase-resetting pathway as that activated by 8-OH-DPAT treatment.
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PMID:Serotonergic mediation of constant light-potentiated nonphotic phase shifting of the circadian locomotor activity rhythm in Syrian hamsters. 1669 Jul 71

Investigations on the effects of the 5-HT agonists and antagonists on the phase of the circadian locomotor activity rhythm of animals kept in constant light conditions (LL) are rare. Therefore the influence of R-(+)-OH-DPAT (5-HT1A receptors agonist) and metergoline (5-HT1/2/7 receptors antagonist) on the phase shift of the locomotor-activity rhythm alone and when combined with dark pulses in mice kept in LL are examined. The results indicate that 8-OH-DPAT administered independently at 12.00CT (Circadian Time) shifted the phase of the circadian rhythm and reinforced the effect of dark pulses on this parameter. 12.00CT was defined arbitrarily as the onset of locomotor activity in constant conditions. Metergoline diminished the phase shifts after dark pulses compared to 8-OH-DPAT. The influence of the serotonin agonist showed that serotonin can reinforce the phase shifting effect of the locomotor activity rhythm after dark pulses in LL condition.
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PMID:Serotonin increases the phase shift of the circadian locomotor activity rhythm in mice after dark pulses in constant light conditions. 1827 52

Serotonin (5-HT) is an important regulator of the mammalian circadian system, and has been implicated in modulating entrained and free-running rhythms, as well as photic and non-photic phase shifting. In general, 5-HT appears to oppose the actions of light on the circadian system of nocturnal rodents. As well, 5-HT mediates, at least in part, some non-photic responses. The 5-HT1A, 1B and 7 receptors regulate these acute responses to zeitgebers. 5-HT also regulates some entrained and free-running properties of the circadian clock. The receptors that contribute to these phenomena have not been fully examined. Here, we use 5-HT1A receptor knockout (KO) mice to examine the response of the mouse circadian system to a variety of lighting conditions, including a normal light-dark cycle (LD), T-cycles, phase advanced LD cycles, constant darkness (DD), constant light (LL) and a 6 hour dark pulse starting at CT5. Relative to wildtype mice, the 5-HT1A receptor KO mice have lower levels of activity during the first 8h of the night/subjective night in LD and LL, later activity onsets on transient days during re-entrainment, shorter free-running periods in LL when housed with wheels, and smaller phase shifts to dark pulses. No differences were noted in activity levels during DD, alpha under any light condition, free-running period in DD, or phase angle of entrainment in LD. While the 5-HT1A receptor plays an important role in regulating photic and non-photic phase shifting, its contribution to entrained and free-running properties of the circadian clock is relatively minor.
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PMID:Effects of lighting condition on circadian behavior in 5-HT1A receptor knockout mice. 2544 24