Role of 5-HT1B receptors in the regulation of extracellular serotonin and dopamine in the dorsal striatum of mice.
To test the hypothesis that 5-HT1B receptors modulate serotonin (5-hydroxytryptamine, 5-HT) and dopamine release in the striatum, we used in vivo microdialysis in mice lacking 5-HT1B receptors. Local administration by reversed microdialysis of the selective 5-HT reuptake inhibitor, fluvoxamine (0.1-10 microM), concentration dependently increased 5-HT to the same extent in wildtype and in 5-HT1B knockout (KO) mice. Fluvoxamine (10 microM) increased dopamine levels similarly in both genotypes. The 5-HT releaser, fenfluramine (50 microM), increased both 5-HT and dopamine levels, but no difference was found between the genotypes. The 5-HT1B receptor agonist, 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one (CP-93,129), reduced 5-HT levels in the wildtype, but not in 5-HT1B KO mice. CP-93,129 at a concentration of 0.5 microM did not affect striatal dopamine outflow in either genotype, whereas dopamine outflow was increased 5-fold by 50 microM CP-93,129 in both genotypes. The CP-93,129-induced dopamine increase was not attenuated by ritanserin, a 5-HT2A/2C receptor antagonist, but was completely blocked by tetrodotoxin, demonstrating that the dopamine release was of neuronal origin. In conclusion, 5-HT1B autoreceptors are functionally present in the mouse striatum, but do not appear to play a significant role in the effects of a selective 5-HT reuptake inhibitor on extracellular 5-HT. In addition, the results in 5-HT1B knockout mice do not support a role of 5-HT1B heteroreceptors in the striatum on dopamine outflow in this brain area of mice.
De Groote
Lotte
L
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Olivier
Berend
B
Westenberg
Herman G M
HG
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D045604:Extracellular Fluid / Q000378:metabolism; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D012701:Serotonin; D004298:Dopamine