Divergent actions of serotonin receptor activation during fictive swimming in frog embryos.
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-HT(7) 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-HT(7) 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.
McLean
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School of Biology, Bute Medical Buildings, University of St Andrews, KY16 9TS St Andrews, Fife, Scotland.
Sillar
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002997:Clomipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D011896:Rana temporaria / Q000196:embryology* / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D013550:Swimming / Q000502:physiology*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002997:Clomipramine; D044282:Receptor, Serotonin, 5-HT1A; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C104425:serotonin 7 receptor