Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies, we showed that localized perfusion of the SCN region with serotonin (5-HT) or the non-selective serotonergic, quipazine, using the microdialysis technique significantly reduced the extracellular concentration of the excitatory amino acid (EAA), glutamate. The present investigation was undertaken to extend these findings by characterizing the effects of various classes of 5-HT receptor ligands on the extracellular glutamate concentration in the SCN. Localized SCN application or i.p. injection of the 5-HT1A receptor agonist, 8-OH-DPAT, during the dark phase (6 h after lights-off) significantly reduced the extracellular glutamate concentration in the SCN region from baseline levels (38.7 +/- 8.7 and 53.4 +/- 11.2%, respectively, of pretreatment values; P < 0.05). The effect of systemically applied 8-OH-DPAT was abolished by i.p. injection of the 5-HT1A receptor antagonist, NAN-190, administered 20 min before the 8-OH-DPAT. Localized perfusion of the SCN with the 5-HT1B receptor agonist, TMFPP, also reduced extracellular glutamate but to a lesser degree than 8-OH-DPAT (80.1 +/- 3.9% of pretreatment levels; P < 0.05). This effect was prevented by i.p. injection of the non-selective 5-HT receptor antagonist, metergoline 20 min before TFMPP perfusion. Localized perfusion of the SCN region with the 5-HT2 and 5-HT3 receptor agonists, alpha-methyl 5-HT and 1-phenylbiguanide, respectively, had little effect on extracellular glutamate (both P > 0.1 vs. baseline). Systemic treatment with NAN-190 alone had little effect on extracellular glutamate, however, similar treatments with metergoline or the 5-HT2 receptor antagonist, ritanserin, induced significant increases extracellular glutamate levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serotonergic inhibition of extracellular glutamate in the suprachiasmatic nuclear region assessed using in vivo brain microdialysis. 782 May 91

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.
 ...
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 previous studies, we showed that light-induced Fos protein expression in the ventrolateral SCN is markedly inhibited by the nonselective serotonergic, quipazine. The present experiments were undertaken to characterize the effects of various serotonin (5-HT) receptor ligands on photic signalling in the SCN. The extent of expression of light-induced Fos-like immunoreactivity (Fos-LI) in the SCN was used as a marker for this response. Exposure of hamsters to a light pulse delivered during the latter part of the dark phase (7 h after lights-off; LD 14:10) elicited an intense expression of Fos-LI in nuclei of cells situated principally in the ventrolateral region of the SCN. Pretreatment with an i.p. injection of the 5-HT1A receptor agonists, 8-OH-DPAT or buspirone, 30 min before the light pulse significantly inhibited the photic expression of Fos-LI (maximal suppression 45.7 +/- 8.1 and 43.0 +/- 1.3%, respectively, both P < 0.01 vs. vehicle controls). Treatment with the 5-HT1A receptor antagonist, NAN-190, administered 15 min before 8-OH-DPAT injection prevented the inhibitory effect of 8-OH-DPAT (100.9 +/- 6.0% vs. controls, P > 0.9). Pretreatment with the 5-HT1B receptor agonist, TFMPP, caused a small but significant suppression of Fos-LI (14.8 +/- 3.5% vs. controls, P < 0.05). In contrast to the significant 5-HT1 receptor agonist effects, pretreatment with 5-HT2 or 5-HT3 receptor agonists, alpha-methyl-5-HT and 1-phenylbiguanide had little suppressive effect on Fos-LI (7.9 +/- 2.1 and 13.0 +/- 5.0% suppression, respectively, both P > 0.1 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modulation of light-induced C-Fos expression in the suprachiasmatic nuclei by 5-HT1A receptor agonists. 819 64

Serotonin (5-HT) has been shown to phase shift circadian rhythms in mammals and to affect responses of the circadian system to light, but it is not clear which receptors are involved in these actions. We found that drugs which act as 5-HT1A receptor agonists suppressed photic responses of hamster SCN cells, but these drugs also exhibit high affinity for the recently cloned 5-HT7 receptor. We therefore studied the effects of 5-HT agonists and antagonists with differential affinities for 5-HT7 and 5-HT1A receptors on responses of hamster SCN cells to retinal illumination. We confirmed that the 5-HT receptor agonists 5-HT, 8-OH-DPAT and 5-CT, dose-dependently reduced photic activation of SCN cells. These effects could be blocked by co-application of antagonists with high affinities for 5-HT7 receptors: ritanserin or clozapine. The 5-HT1A/B/D antagonist, cyanopindolol, which is inactive at 5-HT7 receptors, did not antagonize the actions of 8-OH-DPAT. Selective 5-HT1A antagonists, WAY100635 and p-MPPI, had weak or no antagonist effects on the responses to 8-OH-DPAT in the SCN, but they effectively antagonized the actions of 8-OH-DPAT in the hippocampus. In the cerebellar cortex where few 5-HT7 receptors are present, ritanserin failed to antagonize the effects of 8-OH-DPAT. Our results indicate that the 5-HT7 receptor subtype plays a major role in mediating the effects of 5-HT on photic responses of SCN cells in the hamster.
 ...
PMID:5-HT7 receptors mediate serotonergic effects on light-sensitive suprachiasmatic nucleus neurons. 917 92

The circadian timekeeping system exhibits many functional changes with aging, including a loss of sensitivity to time cues such as systemic injections of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In order to elucidate the neurochemical mechanisms responsible for this age-related loss of sensitivity of the circadian pacemaker to serotonin agonists, the present study used quantitative autoradiography to determine whether aging decreases serotonin receptor populations in male Syrian hamsters. Four neuroanatomical regions that regulate circadian timekeeping were studied (the suprachiasmatic nuclei [SCN], the lateral geniculate nuclei [LGN], and the median raphe nucleus [MRN] and dorsal raphe nucleus [DRN]). The specific binding of [3H]8-OH-DPAT to serotonin7 (5-HT7) and serotonin1A (5-HT1A) receptors was investigated by competitive inhibition with ritanserin and pindolol, respectively. The results showed that the SCN, IGL, MRN, and DRN of the male Syrian hamster exhibited specific binding of [3H]8-OH-DPAT to both the 5-HT7 and 5-HT1A receptors, and that the latter receptor subtype is more abundant in all of these regions. At 17-19 months of age, a 50% decrease in 5-HT7 receptors was found in the DRN but not in any other regions. No significant age-related changes in 5-HT1A receptors were observed in any regions examined. The finding that a marked decrease in 5-HT7 receptors occurs in the DRN at the age previously characterized by loss of sensitivity to 8-OH-DPAT suggests that this region and this receptor subtype play important roles in 8-OH-DPAT induction of circadian phase shifts in vivo and that they constitute an important locus of aging in the circadian timing system.
 ...
PMID:Comparison of the effects of aging on 5-HT7 and 5-HT1A receptors in discrete regions of the circadian timing system in hamsters. 1035 May 28

Serotonin (5-HT) is thought to play a role in regulating nonphotic phase shifts and modulating photic phase shifts of the mammalian circadian system, but results with different species (rats vs. hamsters) and techniques (in vivo vs. in vitro; systemic vs. intracerebral drug delivery) have been discordant. Here we examined the effects of the 5-HT1A/7 agonist 8-OH-DPAT and the 5-HT1/2 agonist quipazine on the circadian system in mice, with some parallel experiments conducted with hamsters for comparative purposes. In mice, neither drug, delivered systemically at a range of circadian phases and doses, induced phase shifts significantly different from vehicle injections. In hamsters, quipazine intraperitoneally (i.p.) did not induce phase shifts, whereas 8-OH-DPAT induced phase shifts after i.p. but not intra-SCN injections. In mice, quipazine modestly increased c-Fos expression in the SCN (site of the circadian pacemaker) during the subjective day, whereas 8-OH-DPAT did not affect SCN c-Fos. In hamsters, both drugs suppressed SCN c-Fos in the subjective day. In both species, both drugs strongly induced c-Fos in the paraventricular nucleus (within-subject positive control). 8-OH-DPAT did not significantly attenuate light-induced phase shifts in mice but did in hamsters (between-species positive control). These results indicate that in the intact mouse in vivo, acute activation of 5-HT1A/2/7 receptors in the circadian system is not sufficient to reset the SCN pacemaker or to oppose phase-shifting effects of light. There appear to be significant species differences in the susceptibility of the circadian system to modulation by systemically delivered serotonergics.
 ...
PMID:Response of the mouse circadian system to serotonin 1A/2/7 agonists in vivo: surprisingly little. 1269 69

Cocaine abuse disrupts reward and homeostatic processes through diverse processes, including those involved in circadian clock regulation. Recently we showed that cocaine administration to mice disrupts nocturnal photic phase resetting of the suprachiasmatic (SCN) circadian clock, whereas administration during the day induces non-photic phase shifts. Importantly, the same effects are seen when cocaine is applied to the SCN in vitro, where it blocks photic-like (glutamate-induced) phase shifts at night and induces phase advances during the day. Furthermore, our previous data suggest that cocaine acts in the SCN by enhancing 5-HT signaling. For example, the in vitro actions of cocaine mimic those of 5-HT and are blocked by the 5-HT antagonist, metergoline, but not the dopamine receptor antagonist, fluphenazine. Although our data are consistent with cocaine acting through enhanced 5-HT signaling, the nonselective actions of cocaine as an antagonist of monoamine transporters raises the question of whether inhibition of the 5-HT transporter (SERT) is key to its circadian effects. Here we investigate this issue using transgenic mice expressing a SERT that exhibits normal 5-HT recognition and transport but significantly reduced cocaine potency (SERT Met172). Circadian patterns of SCN behavioral and neuronal activity did not differ between wild-type (WT) and SERT Met172 mice, nor did they differ in the ability of the 5-HT1A,2,7 receptor agonist, 8-OH-DPAT to reset SCN clock phase, consistent with the normal SERT expression and activity in the transgenic mice. However, (1) cocaine administration does not induce phase advances when administered in vivo or in vitro in SERT Met172 mice; (2) cocaine does not block photic or glutamate-induced phase shifts in SERT Met172 mice; and (3) cocaine does not induce long-term changes in free-running period in SERT Met172 mice. We conclude that SERT antagonism is required for the phase shifting of the SCN circadian clock induced by cocaine.
...
PMID:Cocaine modulates mammalian circadian clock timing by decreasing serotonin transport in the SCN. 2495 Jan 19