Divergent actions of serotonin receptor activation during fictive swimming in frog embryos

D. L. McLean; K. T. Sillar

doi:10.1007/s00359-004-0504-9

Divergent actions of serotonin receptor activation during fictive swimming in frog embryos

D. L. McLean, K. T. Sillar^*

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

We have investigated the pharmacology underlying locomotor system responses to serotonin (5-HT) in embryos of the frog, Rana temporaria, to provide a comparison to studies in embryos of its close relative, Xenopus laevis. Our findings suggest that two divergent mechanisms underlie the modulation of locomotion by 5-HT in Rana. Bath-applied 5-HT or 5-carboxamidotyptamine, a 5-HT_1,5A,7 receptor agonist, can modulate fictive swimming in a dose-dependent manner, increasing burst durations and cycle periods. However, activation of 5-HT_1,7 receptors with R8-OHDPAT or 8-OHDPAT fails to mimic 5-HT, and in some cases exerts exactly the opposite response; decreasing burst durations and cycle periods. Elevating endogenous 5-HT levels by blocking re-uptake with clomipramine transiently increases burst durations. The receptors involved in this endogenous response include 5-HT_1A receptors, as in Xenopus, but also 5-HT₇ receptors. However, like the 8-OHDPAT enantiomers, prolonged re-uptake inhibition can result in a motor response in the opposite direction to exogenous 5-HT. This effect is not reversed by 5-HT_1A and/or 5-HT₇ receptor antagonism, implicating 5-HT_1B/1D receptors. Remarkably, antagonism of these receptors using methiothepin unmasks a dose-dependent response to clomipramine, reminiscent of exogenous 5-HT. Our data suggest that 5-HT_1A,7 and 5-HT _1B/1D receptors act as gain-setters of burst durations, whilst 5-HT_5A receptors are involved in the effects of bath-applied 5-HT on locomotion.

Original language	English (US)
Pages (from-to)	391-402
Number of pages	12
Journal	Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology
Volume	190
Issue number	5
DOIs	https://doi.org/10.1007/s00359-004-0504-9
State	Published - May 2004

Funding

Acknowledgements This work was supported by The Wellcome Trust. We would like to thank J. Simmers, S. Merrywest and J. McDearmid for their valuable comments on previous versions of this manuscript. We are also grateful to anonymous reviewers for their suggestions for improvement. All experiments complied with the Principles of animal care, publication No. 86-23, revised 1985 of the National Institutes of Health and also with UK Home Office regulations regarding animal experimentation as described in the Animals (Scientific Procedures) Act 1986.

Keywords

5-HT
Autoreceptors
Neuromodulation
Rana temporaria
Vertebrate locomotion

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Animal Science and Zoology
Physiology
Behavioral Neuroscience

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10.1007/s00359-004-0504-9

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title = "Divergent actions of serotonin receptor activation during fictive swimming in frog embryos",

abstract = "We have investigated the pharmacology underlying locomotor system responses to serotonin (5-HT) in embryos of the frog, Rana temporaria, to provide a comparison to studies in embryos of its close relative, Xenopus laevis. Our findings suggest that two divergent mechanisms underlie the modulation of locomotion by 5-HT in Rana. Bath-applied 5-HT or 5-carboxamidotyptamine, a 5-HT1,5A,7 receptor agonist, can modulate fictive swimming in a dose-dependent manner, increasing burst durations and cycle periods. However, activation of 5-HT1,7 receptors with R8-OHDPAT or 8-OHDPAT fails to mimic 5-HT, and in some cases exerts exactly the opposite response; decreasing burst durations and cycle periods. Elevating endogenous 5-HT levels by blocking re-uptake with clomipramine transiently increases burst durations. The receptors involved in this endogenous response include 5-HT1A receptors, as in Xenopus, but also 5-HT7 receptors. However, like the 8-OHDPAT enantiomers, prolonged re-uptake inhibition can result in a motor response in the opposite direction to exogenous 5-HT. This effect is not reversed by 5-HT1A and/or 5-HT7 receptor antagonism, implicating 5-HT1B/1D receptors. Remarkably, antagonism of these receptors using methiothepin unmasks a dose-dependent response to clomipramine, reminiscent of exogenous 5-HT. Our data suggest that 5-HT1A,7 and 5-HT 1B/1D receptors act as gain-setters of burst durations, whilst 5-HT5A receptors are involved in the effects of bath-applied 5-HT on locomotion.",

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author = "McLean, {D. L.} and Sillar, {K. T.}",

note = "Funding Information: Acknowledgements This work was supported by The Wellcome Trust. We would like to thank J. Simmers, S. Merrywest and J. McDearmid for their valuable comments on previous versions of this manuscript. We are also grateful to anonymous reviewers for their suggestions for improvement. All experiments complied with the Principles of animal care, publication No. 86-23, revised 1985 of the National Institutes of Health and also with UK Home Office regulations regarding animal experimentation as described in the Animals (Scientific Procedures) Act 1986.",

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N2 - We have investigated the pharmacology underlying locomotor system responses to serotonin (5-HT) in embryos of the frog, Rana temporaria, to provide a comparison to studies in embryos of its close relative, Xenopus laevis. Our findings suggest that two divergent mechanisms underlie the modulation of locomotion by 5-HT in Rana. Bath-applied 5-HT or 5-carboxamidotyptamine, a 5-HT1,5A,7 receptor agonist, can modulate fictive swimming in a dose-dependent manner, increasing burst durations and cycle periods. However, activation of 5-HT1,7 receptors with R8-OHDPAT or 8-OHDPAT fails to mimic 5-HT, and in some cases exerts exactly the opposite response; decreasing burst durations and cycle periods. Elevating endogenous 5-HT levels by blocking re-uptake with clomipramine transiently increases burst durations. The receptors involved in this endogenous response include 5-HT1A receptors, as in Xenopus, but also 5-HT7 receptors. However, like the 8-OHDPAT enantiomers, prolonged re-uptake inhibition can result in a motor response in the opposite direction to exogenous 5-HT. This effect is not reversed by 5-HT1A and/or 5-HT7 receptor antagonism, implicating 5-HT1B/1D receptors. Remarkably, antagonism of these receptors using methiothepin unmasks a dose-dependent response to clomipramine, reminiscent of exogenous 5-HT. Our data suggest that 5-HT1A,7 and 5-HT 1B/1D receptors act as gain-setters of burst durations, whilst 5-HT5A receptors are involved in the effects of bath-applied 5-HT on locomotion.

AB - We have investigated the pharmacology underlying locomotor system responses to serotonin (5-HT) in embryos of the frog, Rana temporaria, to provide a comparison to studies in embryos of its close relative, Xenopus laevis. Our findings suggest that two divergent mechanisms underlie the modulation of locomotion by 5-HT in Rana. Bath-applied 5-HT or 5-carboxamidotyptamine, a 5-HT1,5A,7 receptor agonist, can modulate fictive swimming in a dose-dependent manner, increasing burst durations and cycle periods. However, activation of 5-HT1,7 receptors with R8-OHDPAT or 8-OHDPAT fails to mimic 5-HT, and in some cases exerts exactly the opposite response; decreasing burst durations and cycle periods. Elevating endogenous 5-HT levels by blocking re-uptake with clomipramine transiently increases burst durations. The receptors involved in this endogenous response include 5-HT1A receptors, as in Xenopus, but also 5-HT7 receptors. However, like the 8-OHDPAT enantiomers, prolonged re-uptake inhibition can result in a motor response in the opposite direction to exogenous 5-HT. This effect is not reversed by 5-HT1A and/or 5-HT7 receptor antagonism, implicating 5-HT1B/1D receptors. Remarkably, antagonism of these receptors using methiothepin unmasks a dose-dependent response to clomipramine, reminiscent of exogenous 5-HT. Our data suggest that 5-HT1A,7 and 5-HT 1B/1D receptors act as gain-setters of burst durations, whilst 5-HT5A receptors are involved in the effects of bath-applied 5-HT on locomotion.

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Divergent actions of serotonin receptor activation during fictive swimming in frog embryos

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