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5-HT1B Receptor

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Gary E. Pickard – One of the best experts on this subject based on the ideXlab platform.

  • Photic entrainment is altered in the 5-HT1B Receptor knockout mouse.
    Journal of biological rhythms, 2006
    Co-Authors: Patricia J. Sollars, Malcolm D. Ogilvie, Anne M. Simpson, Gary E. Pickard
    Abstract:

    The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives glutamatergic afferents from the retina and serotonergic afferents from the midbrain. Activation of presynaptic serotonin 1B (5-HT1B) Receptors on retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and light-induced behavioral phase shifts. To assess the role of 5-HT1B Receptors in photic entrainment, 5-HT1B Receptor knockout (5-HT1B KO) and wild-type (WT) mice were maintained in non-24 h L:D cycles (T cycles). WT mice entrained to T = 21 h and T = 22 h cycles, whereas 5-HT1B KO animals did not. 5-HT1B KO animals did entrain to T = 23 h and T = 26 h cycles, although their phase angle of entrainment was altered compared to WT animals. 5-HT1B KO mice were significantly more phase delayed under T = 23 h conditions and significantly more phase advanced under T = 26 h conditions compared to WT mice. When 5-HT1B KO mice were housed in a T = 23 h short-day photoperiod (9.5L:13.5D), the delayed phase angle of entrainment was more pronounced. Light-induced phase shifts were reduced in 5-HT1B KO mice, consistent with their behavior in T cycles, suggesting an attenuated response to light. Based on previous work, this attenuated response to light might not have been predicted but can be explained by consideration of GABAergic mechanisms within the SCN. Phase-delayed circadian rhythms during the short days of winter are characteristic of patients suffering from seasonal affective disorder, and 5-HT has been implicated in its pathophysiology. The 5-HT1B KO mouse may be useful for investigating the altered entrainment evident during this serious mood disorder.

  • 5-HT1B Receptor-mediated presynaptic inhibition of GABA release in the suprachiasmatic nucleus.
    Journal of neurophysiology, 2005
    Co-Authors: Jayne R. Bramley, Patricia J. Sollars, Gary E. Pickard, F. Edward Dudek
    Abstract:

    The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic Receptors on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B Receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT1B Receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat and mouse SCN neurons in hypothalamic slices. Using CsCl-containing microelectrodes with QX314, we isolated mPSCs that were sensitive to the GABAA Receptor antagonist, bicuculline. Bath application of CP-93,129 (1 μM) decreased the frequency of mIPSCs by an average of 22% (n = 7) in rat SCN neurons and by an average of 30% (n = 8) in mouse SCN neurons with n…

  • 5-HT1B Receptor Knockout Mice Exhibit an Enhanced Response to Constant Light:
    Journal of biological rhythms, 2002
    Co-Authors: Patricia J. Sollars, Malcolm D. Ogilvie, Michael A. Rea, Gary E. Pickard
    Abstract:

    Serotonin (5-HT) can act presynaptically at 5-HT1B Receptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT1B Receptor agonists (1) inhibit light-induced phase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve-evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT1B presynaptic Receptors would result in an amplified response of the SCN to light, the period (τ) of the cir- cadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT1B Receptor knockout (KO) mice and genetically matched wild- type animals. Under constant light (LL) conditions, the τ of 5-HT1B Receptor KO mice was significantly greater than the τ of wild-type mice. A quantitative analy- sis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in τ was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT1B Receptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT1B Receptor KO mice in the rate of reentrainment t oa6h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5- HT1B Receptor KO mice to LL conditions is consistent with the hypothesis that the endogenous activation of 5-HT1B presynaptic Receptors modulates circadian behavior by attenuating photic input to the SCN.

Katarina Varnas – One of the best experts on this subject based on the ideXlab platform.

Lars Edvinsson – One of the best experts on this subject based on the ideXlab platform.

Patricia J. Sollars – One of the best experts on this subject based on the ideXlab platform.

  • Photic entrainment is altered in the 5-HT1B Receptor knockout mouse.
    Journal of biological rhythms, 2006
    Co-Authors: Patricia J. Sollars, Malcolm D. Ogilvie, Anne M. Simpson, Gary E. Pickard
    Abstract:

    The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives glutamatergic afferents from the retina and serotonergic afferents from the midbrain. Activation of presynaptic serotonin 1B (5-HT1B) Receptors on retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and light-induced behavioral phase shifts. To assess the role of 5-HT1B Receptors in photic entrainment, 5-HT1B Receptor knockout (5-HT1B KO) and wild-type (WT) mice were maintained in non-24 h L:D cycles (T cycles). WT mice entrained to T = 21 h and T = 22 h cycles, whereas 5-HT1B KO animals did not. 5-HT1B KO animals did entrain to T = 23 h and T = 26 h cycles, although their phase angle of entrainment was altered compared to WT animals. 5-HT1B KO mice were significantly more phase delayed under T = 23 h conditions and significantly more phase advanced under T = 26 h conditions compared to WT mice. When 5-HT1B KO mice were housed in a T = 23 h short-day photoperiod (9.5L:13.5D), the delayed phase angle of entrainment was more pronounced. Light-induced phase shifts were reduced in 5-HT1B KO mice, consistent with their behavior in T cycles, suggesting an attenuated response to light. Based on previous work, this attenuated response to light might not have been predicted but can be explained by consideration of GABAergic mechanisms within the SCN. Phase-delayed circadian rhythms during the short days of winter are characteristic of patients suffering from seasonal affective disorder, and 5-HT has been implicated in its pathophysiology. The 5-HT1B KO mouse may be useful for investigating the altered entrainment evident during this serious mood disorder.

  • 5-HT1B Receptor-mediated presynaptic inhibition of GABA release in the suprachiasmatic nucleus.
    Journal of neurophysiology, 2005
    Co-Authors: Jayne R. Bramley, Patricia J. Sollars, Gary E. Pickard, F. Edward Dudek
    Abstract:

    The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic Receptors on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B Receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT1B Receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat and mouse SCN neurons in hypothalamic slices. Using CsCl-containing microelectrodes with QX314, we isolated mPSCs that were sensitive to the GABAA Receptor antagonist, bicuculline. Bath application of CP-93,129 (1 μM) decreased the frequency of mIPSCs by an average of 22% (n = 7) in rat SCN neurons and by an average of 30% (n = 8) in mouse SCN neurons with n…

  • 5-HT1B Receptor Knockout Mice Exhibit an Enhanced Response to Constant Light:
    Journal of biological rhythms, 2002
    Co-Authors: Patricia J. Sollars, Malcolm D. Ogilvie, Michael A. Rea, Gary E. Pickard
    Abstract:

    Serotonin (5-HT) can act presynaptically at 5-HT1B Receptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT1B Receptor agonists (1) inhibit light-induced phase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve-evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT1B presynaptic Receptors would result in an amplified response of the SCN to light, the period (τ) of the cir- cadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT1B Receptor knockout (KO) mice and genetically matched wild- type animals. Under constant light (LL) conditions, the τ of 5-HT1B Receptor KO mice was significantly greater than the τ of wild-type mice. A quantitative analy- sis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in τ was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT1B Receptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT1B Receptor KO mice in the rate of reentrainment t oa6h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5- HT1B Receptor KO mice to LL conditions is consistent with the hypothesis that the endogenous activation of 5-HT1B presynaptic Receptors modulates circadian behavior by attenuating photic input to the SCN.

Christer Halldin – One of the best experts on this subject based on the ideXlab platform.

  • a randomized placebo controlled pet study of ketamine s effect on serotonin 1b Receptor binding in patients with ssri resistant depression
    Translational Psychiatry, 2020
    Co-Authors: Mikael Tiger, Per Svenningsson, Emma R. Veldman, Carl Johan Ekman, Christer Halldin, J M Lundberg
    Abstract:

    The glutamate N-methyl-d-aspartate Receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine’s mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be dependent on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and the serotonin (5-HT)1B Receptor. Low 5-HT1B Receptor binding in limbic brain regions is a replicated finding in MDD. In non-human primates, AMPA-dependent increase in 5-HT1B Receptor binding in the ventral stristriatum (VST) has been demonstrated after ketamine infusion. Thirty selective serotonin reuptake inhibitor-resistant MDD patients were recruited via advertisement and randomized to double-blind monotherapy with 0.5 mg/kg ketamine or placebo infusion. The patients were examined with the 5-HT1B Receptor selective radioligand [11C]AZ10419369 and positron emission tomotomography (PET) before and 24–72 h after treatment. 5-HT1B Receptor binding did not significantly alter in patients treated with ketamine compared with placebo. An increase in 5-HT1B Receptor binding with 16.7 % (p = 0.036) was found in the hippocampus after one ketamine treatment. 5-HT1B Receptor binding in VST at baseline correlated with MDD symptom ratings (r = −0.426, p = 0.019) and with reduction of depressive symptoms with ketamine (r = −0.644, p = 0.002). In conclusion, reduction of depressive symptoms in MDD patients after ketamine treatment is correlated inversely with baseline 5-HT1B Receptor binding in VST. Further studies examining the role of 5-HT1B Receptors in the antidepressant mechanism of action of ketamine should be conducted, homing in on the 5-HT1B Receptor as an MDD treatment response marker.

  • 5-HT1B Receptor imaging and cognition: a positron emission tomography study in control subjects and Parkinson’s disease patients.
    Synapse (New York N.Y.), 2015
    Co-Authors: Andrea Varrone, Per Svenningsson, Christer Halldin, Petter Marklund, Helena Fatouros-bergman, Anton Forsberg, Lars-göran Nilsson, Lars Farde
    Abstract:

    Introduction The serotonin 5-HT1B Receptor subtype is involved in the modulation of serotonin release and is a target of interest for neuroReceptor imaging. Previous studies have shown that the serotonin system is affected in Parkinson‘s disease (PD). Cognitive function, frequently impaired in PD, has been linked to the serotonin system. The aim of this study was to examine whether 5-HT1B Receptor availability in the brain of healthy subjects and PD patients is associated with measures of cognitive function. Methods Twelve control subjects and ten PD patients with normal mini-mental state examination scores were included in this study. Cognitive function was evaluated by assessment of semantic, episodic, and working memory, as well as fluency and visual attention. Creative ability, a measure of divergent thinking, was examined with the alternative uses of objects task. PET measurements were performed with the 5-HT1B Receptor-radioligand [11C]AZ10419369 using the HRRT system. Results PD patients showed statistically significant lower measures of semantic and episodic memory, as well as creative ability, compared with control subjects. Statistically significant positive correlations were found in control subjects between creative ability and average 5-HT1B Receptor availability in grey matter, and in PD patients between scores of Beck DeprDepression Inventory-II and creative ability. Conclusion Though creativity has been conventionally linked to dopamine function, our findings in control subjects suggest a link between 5-HT1B Receptor availability and creative ability. In PD patients, creative ability was significantly associated with depressive symptoms but not with 5-HT1B Receptor availability. This finding deserves further investigation in future studies. Synapse 69:365–374, 2015. © 2015 Wiley Periodicals, Inc.

  • A possible mechanism of the nucleus accumbens and ventral pallidum 5-HT1B Receptors underlying the antidepressant action of ketamine: a PET study with macaques
    Translational Psychiatry, 2014
    Co-Authors: H Yamanaka, Christer Halldin, C Yokoyama, H Mizuma, S Kurai, S J Finnema, H Onoe
    Abstract:

    Ketamine is a unique anesthetic reagent known to produce various psychotic symptoms. Ketamine has recently been reported to elicit a long-lasting antidepressant effect in patients with major depression. Although recent studies provide insight into the molecular mechanisms of the effects of ketamine, the antidepressant mechanism has not been fully elucidated. To understand the involvement of the brain serotonergic system in the actions of ketamine, we performed a positron emission tomotomography (PET) study on non-human primates. Four rhesus monkeys underwent PET studies with two serotonin (5-HT)-related PET radioligands, [^11C]AZ10419369 and [^11C]DASB, which are highly selective for the 5-HT1B Receptor and serotonin transporter (SERT), respectively. Voxel-based analysis using standardized brain images revealed that ketamine administration significantly increased 5-HT1B Receptor binding in the nucleus accumbens and ventral pallidum, whereas it significantly reduced SERT binding in these brain regions. Fenfluramine, a 5-HT releaser, significantly decreased 5-HT1B Receptor binding, but no additional effect was observed when it was administered with ketamine. Furthermore, pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), a potent antagonist of the glutamate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) Receptor, blocked the action of ketamine on the 5-HT1B Receptor but not SERT binding. This indicates the involvement of AMPA Receptor activation in ketamine-induced alterations of 5-HT1B Receptor binding. Because NBQX is known to block the antidepressant effect of ketamine in rodents, alterations in the serotonergic neurotransmission, particularly upregulation of postsynaptic 5-HT1B Receptors in the nucleus accumbens and ventral pallidum may be critically involved in the antidepressant action of ketamine.