The Journal of Neuroscience, 2001, 21:RC192:1-6
RAPID COMMUNICATION
Psychostimulants Differentially Regulate Serotonin Transporter
Expression in Thalamocortical Neurons
Terri L.
Whitworth,
Laura C.
Herndon, and
Michael W.
Quick
Department of Neurobiology, University of Alabama at Birmingham,
Birmingham, Alabama 35294
5-HT transporters (SERTs) are transiently expressed in
thalamocortical neurons during development, permitting these
glutamatergic neurons to co-release 5-HT as a "borrowed"
transmitter. The high level of SERT expression in these neurons is
likely important in the serotonergic modulation of neocortical circuits
and provides a system for examining endogenous SERT regulation. We
tested the hypothesis that developmental expression of SERT in
thalamocortical neurons is regulated by psychostimulants that are
agonists and antagonists of SERT. Cultured thalamocortical neurons from
embryonic day 18 rats were examined for SERT expression until P15. In
untreated cultures, SERT protein levels peaked at postnatal day 3 (P3)
and were absent by P10. Chronic treatment with SERT substrates (5-HT, 3,4-methylenedioxymethamphetamine) increased both peak SERT
protein levels (fourfold) and the time course of SERT expression. SERT substrates also shifted the relative functional expression of SERT by
redistributing intracellular SERT protein to the plasma membrane. The
subcellular redistribution was prevented by PKC activators. SERT
antagonists (e.g., fluoxetine, cocaine) reduced total SERT
expression levels and the time course of SERT expression. These data
(1) show that endogenous SERT is differentially regulated by 5-HT and
psychostimulants, (2) indicate that SERT modulation occurs via changes
in both total SERT protein levels and subcellular redistribution of the
transporter, and (3) suggest that some of the actions of drugs of abuse
in neocortical development may be attributable to alterations in SERT
expression and concomitant changes in 5-HT signaling.
Key words:
cortex; development; drug abuse; monoamine; regulation; uptake
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