Serotonin infusions inhibit sensory input from the dural vasculature.
Intravenous infusions of serotonin (5-hydroxtryptamine creatinine sulphate, 5HT, 50-300 microg/kg/min) in cats reversibly inhibited the responses of cervical spinal cord neurons to electrical stimulation of the superior sagittal sinus. Inhibition developed over 20-30 min and resolved over the same time course, suggesting a dependence on accumulation of 5HT in the central nervous system. Inhibition was suppressed by prior intravenous injection of the 5HT antagonists methysergide (1 mg/kg) and methiothepin (1 mg/kg). Infusions of 5HT (50 microg/kg/min) caused a rise in whole blood levels of 5HT by a factor of 1.5 of control values. 5HT levels in platelet-free plasma rose by a factor of 50. Levels of 5HT and 5 hydroxyindole acetic acid released into the cerebrospinal fluid rose significantly. The results suggest that earlier clinical observations that 5HT infusions can ameliorate the pain of migraine may not have been due to cranial vasoconstriction alone, but could have involved a central action of 5HT.
Lambert
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GA
Institute of Neurological Sciences, The Prince Henry Hospital, University of New South Wales, Little Bay, Australia. G.Lambert@unsw.edu.au
Shimomura
T
T
Boers
P M
PM
Gordon
V
V
Donaldson
C
C
Zagami
A S
AS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D003392:Cranial Sinuses; D004388:Dura Mater / Q000098:blood supply*; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects*; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D007262:Infusions, Intravenous; D008719:Methiothepin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology* / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000503:physiopathology*; D013599:Systole / Q000187:drug effects; D014278:Trigeminal Nuclei / Q000503:physiopathology
D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008719:Methiothepin; D008784:Methysergide