Neuromodulatory Neurotransmitters Influence LTP-like Plasticity in Human Cortex: a Pharmaco-TMS Study

Alexei Korchounov (1) , Ulf Ziemann (1)

1 Neurology

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. Non-invasive 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 randomised 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, while 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.

Mots clés: Acetylcholine; Dopamine; Catecholamines; Plasticity; Human motor cortex; Transcranial magnetic stimulation; Long-term potentiation

Alexei Korchounov, Ulf Ziemann. Neuromodulatory Neurotransmitters Influence LTP-like Plasticity in Human Cortex: a Pharmaco-TMS Study. Neuropsychopharmacology, 2011, ⟨10.1038/npp.2011.75⟩. ⟨hal-00638138⟩