In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate.
Although the 5-HT(6) receptor subtype was identified some 5 years ago, very little is known about its function within the brain. Here we demonstrate, for the first time, the neurochemical effects of a selective 5-HT(6) receptor ligand. Using in vivo microdialysis in the freely moving rat, we evaluated the effects of the selective 5-HT(6) receptor antagonist SB-271046 by simultaneous measurement of 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (NA), glutamate and aspartate from the striatum and frontal cortex. SB-271046 did not alter basal levels of 5-HT, DA and NA in either brain region. Similarly, there was no change basal levels of either of the excitatory amino acids within the striatum. In contrast, administration of SB-271046 (10 mg kg(-1) s.c.) produced a significant (P<0.05), tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex, reaching maximum values of 375.4+/-82.3 and 215. 3+/-62.1% of preinjection values, respectively.
Dawson
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LA
Neuroscience Discovery Research, Wyeth, CN8000, Princeton, New Jersey, NJ 08543, USA. Dawsonl@war.wyeth.com
Nguyen
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Li
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D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D015306:Biogenic Monoamines; D018846:Excitatory Amino Acids; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; C117443:SB 271046