Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

• Published in: Neuropsychopharmacology 2011-08, Vol.36 (9), p.1894-1902
• Main Authors: Korchounov, Alexei, Ziemann, Ulf
• Format: Article
• Language: English
• Subjects: 631/378/2591/2592; 631/378/2632/1663; 631/378/548/1964; 631/92/436/108; Adolescent; Adrenergic Agonists - pharmacology; Adrenergic Antagonists - pharmacology; Adult; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Cholinergic Agonists - pharmacology; Cholinergic Antagonists - pharmacology; Cross-Over Studies; Dopamine; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Double-Blind Method; Drug dosages; Electromyography; Female; Humans; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Medical sciences; Medicine; Medicine & Public Health; Memory - drug effects; Memory - physiology; Memory Disorders - chemically induced; Memory Disorders - physiopathology; Motor Cortex - chemistry; Motor Cortex - drug effects; Motor Cortex - physiology; Neurosciences; Neurotransmitter Agents - physiology; Neurotransmitters; Original; original-article; Pharmacotherapy; Psychiatry; Transcranial magnetic stimulation; Transcranial Magnetic Stimulation - methods; Young Adult
• ISSN: 0893-133X; 1740-634X; 0007-0920
• DOI: 10.1038/npp.2011.75

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.