Regulation of serotonin release in the frontal cortex and ventral hippocampus of homozygous mice lacking 5-HT1B receptors: in vivo microdialysis studies.
To assess the involvement of the serotonin receptor subtype 5-HT1B as terminal autoreceptor regulating 5-HT release in mice, we compared basal values and potassium-evoked changes of extracellular 5-HT levels obtained by in vivo microdialysis in two serotoninergic terminal projection areas of conscious wild-type mice with those measured in homozygous mutant mice lacking the gene encoding the 5-HT1B receptor. In the frontal cortex and ventral hippocampus, basal and K+-evoked 5-HT release did not differ between the two strains of mice studied. The infusion via reverse microdialysis of the selective 5-HT1B receptor agonist CP-93,129 (500 nM) decreased significantly K+-evoked 5-HT release in the frontal cortex (by -44%) and ventral hippocampus (by -32%) of wild-type mice but had no effect in mutants. In a similar manner, the mixed 5-HT1B-5-HT1D receptor agonist sumatriptan (800 nM) decreased significantly K+-evoked 5-HT release in the frontal cortex (by -46%) of wild-type mice but had no effect in mutants. These results demonstrated that 5-HT1B knockout mice are not as sensitive to full (CP-93,129) and mixed (sumatriptan) 5-HT1B receptor agonists as are wild-type mice. These data provide in vivo evidence that, in mice, 5-HT1B, but not 5-HT1D, autoreceptors inhibit 5-HT release at nerve terminals located in the frontal cortex and ventral hippocampus.
Trillat
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AC
Laboratoire de Neuropharmacologie, Faculté de Pharmacie, Université de Paris-Sud, Châtenay-Malabry, France.
Malagié
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I
Scearce
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K
Pons
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D
Anmella
M C
MC
Jacquot
C
C
Hen
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R
Gardier
A M
AM
D000818:Animals; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006720:Homozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017551:Microdialysis; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000172:deficiency* / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology
D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D012701:Serotonin; D018170:Sumatriptan; D011188:Potassium