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Lack of localization of 5‐HT 6 receptors on cholinergic neurons: implication of multiple neurotransmitter systems in 5‐HT 6 receptor‐mediated acetylcholine release
Author(s) -
Marcos Beatriz,
GilBea Francisco J.,
Hirst Warren D.,
GarcíaAlloza Mónica,
Ramírez María J.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05003.x
Subject(s) - acetylcholine , cholinergic , neurotransmitter , medicine , chemistry , endocrinology , 5 ht receptor , striatum , dopamine , receptor antagonist , glutamate receptor , receptor , neuroscience , serotonin , biology , antagonist
The involvement of the cholinergic system in learning and memory together with the cognitive enhancing properties of 5‐HT 6 receptor antagonists led us to study the relationship between 5‐HT 6 receptors and cholinergic neurotransmission. A selective cholinergic lesion, induced by injection of the immunotoxin 192‐IgG‐Saporin into the nucleus basalis magnocellularis, failed to alter the density of 5‐HT 6 receptor mRNA or protein expression in the deafferentated frontal cortex, suggesting that 5‐HT 6 receptors are not located on cholinergic neurons. The 5‐HT 6 receptor antagonist SB‐357134 (0.001–1 µ m ) induced a concentration‐dependant K + ‐evoked [ 3 H]acetylcholine (ACh) release in vitro in rat cortical and striatal slices, which was blocked by tetrodotoxin. SB‐357134, up to 1 µ m , stimulated glutamate release in cortical and striatal slices. In the cortex, riluzole (1 µ m ) blocked the SB‐357134‐induced K + ‐stimulated [ 3 H]ACh release, and simultaneous administration of MK‐801 (1 µ m ) and SB‐357134 (0.05 µ m ) elicited an increase in K + ‐evoked ACh release. In the striatum, SB‐357134, 1 µ m , decreased dopamine release, and the increase in K + ‐evoked [ 3 H]ACh release induced by 5‐HT 6 receptor blockade was reversed by the D 1 receptor antagonist, SCH23390 (1 µ m ). In both the frontal cortex and striatum, bicuculline, 1 µ m , showed no effect on SB‐357134‐evoked [ 3 H]ACh. These results are discussed in terms of neurochemical mechanisms involved in 5‐HT 6 receptor functions.