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The Journal of Neuroscience, May 1, 2002, 22(9):3638-3644
Overcoming the Effects of Stress on Synaptic Plasticity in the
Intact Hippocampus: Rapid Actions of Serotonergic and Antidepressant
Agents
Alison C.
Shakesby1,
Roger
Anwyl2, and
Michael
J.
Rowan1
Departments of 1 Pharmacology and Therapeutics and
2 Physiology, Trinity College, Dublin 2, Ireland
Acute inescapable stress dramatically affects the inducibility of
plasticity at glutamatergic synapses in the intact hippocampus. The
present study examined the involvement of serotonergic mechanisms in
mediating and modulating the block of long-term potentiation (LTP) in
the CA1 area of anesthetized rats after exposure to an elevated
platform stress. Fluoxetine and fenfluramine, agents that raise
hippocampal extracellular 5-HT concentration, blocked the induction of
LTP in nonstressed animals, thus mimicking the effect of stress. In
contrast, (±)-tianeptine, a drug that decreases 5-HT levels, had no
effect on LTP induction in nonstressed animals. Remarkably, (±)
administration of tianeptine after the stress rapidly overcame the
block of LTP induction without affecting baseline excitatory
transmission. Consistent with a reduction of 5-HT levels being
responsible for this effect of tianeptine, the ( ) enantiomer, which
is associated with the 5-HT uptake enhancing action of (±)-tianeptine,
also caused a recovery of the induction of LTP in previously stressed
animals, whereas the relatively inactive (+) enantiomer had no effect.
Furthermore, fluoxetine prevented the effect of tianeptine in stressed
animals. These findings show that antidepressants have rapid and
powerful interactions with the mechanisms controlling the persistence
of the block of LTP by inescapable stress.
Key words:
acute stress; synaptic plasticity; long-term
potentiation; 5-hydroxytryptamine; fluoxetine; fenfluramine; tianeptine; in vivo; antidepressant
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293638-07$05.00/0
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