Although the 5‐HT6 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‐HT6 receptor ligand. Using in vivo microdialysis in the freely moving rat, we evaluated the effects of the selective 5‐HT6 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.
British Journal of Pharmacology (2000) 130, 23–26; doi:
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