Neuromodulatory neurotransmitters influence LTP-like plasticity in human cortex:
a pharmaco-TMS study.
Author(s): Korchounov A, Ziemann U.
Affiliation(s): Department of Neurology, Goethe-University Frankfurt, Frankfurt, Germany.
Publication date & source: 2011, Neuropsychopharmacology. , 36(9):1894-902
Long-term potentiation (LTP) of synaptic efficacy is considered a fundamental
mechanism of learning and memory. At the cellular level a large body of evidence
demonstrated that the major neuromodulatory neurotransmitters dopamine (DA),
norepinephrine (NE), and acetylcholine (ACh) influence LTP magnitude. Noninvasive
brain stimulation protocols provide the opportunity to study LTP-like plasticity
at the systems level of human cortex. Here we applied paired associative
stimulation (PAS) to induce LTP-like plasticity in the primary motor cortex of
eight healthy subjects. In a double-blind, randomized, placebo-controlled,
crossover design, the acute effects of a single oral dose of the neuromodulatory
drugs cabergoline (DA agonist), haloperidol (DA antagonist), methylphenidate
(indirect NE agonist), prazosine (NE antagonist), tacrine (ACh agonist), and
biperiden (ACh antagonist) on PAS-induced LTP-like plasticity were examined. The
antagonists haloperidol, prazosine, and biperiden depressed significantly the
PAS-induced LTP-like plasticity observed under placebo, whereas the agonists
cabergoline, methylphenidate, and tacrine had no effect. Findings demonstrate
that antagonists in major neuromodulatory neurotransmitter systems suppress
LTP-like plasticity at the systems level of human cortex, in accord with evidence
of their modulating action of LTP at the cellular level. This provides further
supportive evidence for the known detrimental effects of these drugs on
LTP-dependent mechanisms such as learning and memory.
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