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Non‐linear relationship between 5‐HT transporter gene expression and frequency sensitivity of 5‐HT signals
Author(s) -
Jennings Katie Ann,
Lesch KlausPeter,
Sharp Trevor,
Cragg Stephanie Jane
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07001.x
Subject(s) - endocrinology , medicine , extracellular , chemistry , stimulus (psychology) , gene expression , 5 ht receptor , electrophysiology , transporter , receptor , neuroscience , biology , serotonin , psychology , gene , biochemistry , psychotherapist
J. Neurochem. (2010) 115 , 965–973. Abstract Much evidence suggests that variation in expression of the 5‐hydroxytryptamine (5‐HT) transporter (5‐HTT) is linked to risk of psychiatric illness, but the neurobiological basis of this association is uncertain. In this study, we investigated the impact of variation in 5‐HTT expression on subsecond fluctuations in extracellular 5‐HT concentrations ([5‐HT] o ). Stimulus‐evoked [5‐HT] o was detected using fast‐scan cyclic voltammetry at carbon‐fibre microelectrodes in the substantia nigra in brain slices from 5‐HTT knockout (KO) and 5‐HTT over‐expressing (OE) mice. Compared with wild‐type (WT) controls, evoked [5‐HT] o was greater in KO and less in OE mice. In WT controls, evoked [5‐HT] o was frequency‐sensitive; however, in both KO and OE mice, evoked [5‐HT] o showed a striking loss of frequency sensitivity. The latter was observed in WT mice after application of a 5‐HTT blocker. These data show that while variation in 5‐HTT expression modified the peak magnitude of [5‐HT] o evoked by any given stimulus in a gene dose dependent manner, there was a non‐linear relationship between 5‐HTT expression and frequency sensitivity. Overall, the findings suggest that variation in 5‐HTT expression has a marked effect on frequency sensitivity which is a fundamental property of normal 5‐HT transmission.