Pharmacological Manipulation of Long-term Potentiation and Cortical Inhibition from the Dorsolateral Prefrontal Cortex, a Model to Understand Cognitive Deficits of Schizophrenia

Several studies have assessed the pharmacological modulation of cortical inhibition (CI) and long-term potentiation (LTP) using transcranial magnetic stimulation (TMS) from the motor cortex and recorded these effects through surface electromyography (EMG). However, recording CI and LTP from the dorsolateral prefrontal cortex (DLPFC), a cortical region that is more closely associated with the pathophysiology of severe psychiatric disorders including schizophrenia were previously not done. Objectives: This study, therefore, was designed to investigate whether CI, indexed by long interval cortical inhibition (LICI), and LTP measured using paired associative stimulation (PAS) could be modulated and measured from the DLPFC in healthy participants through the use of TMS combined with electroencephalography ( EEG ) using a placebo-controlled, randomized double-blinded crossover study design. Methods: 12 healthy participants were given a single oral dose of baclofen, a GABAB agonist, dextromethorphan, a NMDA antagonist, L-DOPA, a dopamine precursor, rivastigmine, an acetylcholine esterase inhibitor for each arm of the study. Results: LICI was enhanced and suppressed by increasing GABAergic tone and cholinergic tone, respectively. LTP was increased by enhancing cholinergic tone and dopaminergic tone and abolished when NMDA receptors were blocked. Conclusion: These results are important and have the potential for therapeutic application in manipulating neural plasticity and CI in the DLPFC to treat a variety of conditions, including depression, Parkinson's disease, and schizophrenia.Ph.D.2019-11-09 00:00:0