AUTHOR=Salavati Bahar, Daskalakis Zafiris J., Zomorrodi Reza, Blumberger Daniel M., Chen Robert, Pollock Bruce G., Rajji Tarek K. TITLE=Pharmacological Modulation of Long-Term Potentiation-Like Activity in the Dorsolateral Prefrontal Cortex JOURNAL=Frontiers in Human Neuroscience VOLUME=12 YEAR=2018 URL=https://www.frontiersin.org/articles/10.3389/fnhum.2018.00155 DOI=10.3389/fnhum.2018.00155 ISSN=1662-5161 ABSTRACT=Background: Long-term potentiation (LTP) depends on glutamatergic neurotransmission and is modulated by cholinergic, dopaminergic and GABAergic inputs. Paired associative stimulation (PAS) is a neurostimulation paradigm that, when combined with electroencephalography (EEG), assesses LTP-like activity (PAS-induced LTP) in the dorsolateral prefrontal cortex (DLPFC). Thus, we conducted a study to assess the role of cholinergic, dopaminergic, GABAergic and glutamatergic neurotransmission on PAS-induced LTP in the DLPFC. We hypothesized that increasing the dopaminergic tone with L-DOPA and the cholinergic tone with rivastigmine will enhance PAS-induced LTP, while increasing the GABAergic tone with baclofen and inhibiting glutamatergic neurotransmission with dextromethorphan will reduce it compared to placebo.Methods: In this randomized controlled, double-blind cross-over within-subject study, 12 healthy participants received five sessions of PAS to the DLPFC in a random order, each preceded by the administration of placebo or one of the four active drugs. PAS-induced LTP was assessed after each drug administration and compared to PAS-induced LTP after placebo.Results: As predicted, L-DOPA and rivastigmine resulted in enhanced PAS-induced LTP in the DLPFC and dextromethorphan inhibited it compared to placebo. In contrast, baclofen did not significantly suppress PAS-induced LTP compared to placebo.Conclusions: This study provides a novel approach to study DLPFC neuroplasticity and its modulation in patients with brain disorders that are associated with abnormalities in these neurochemical systems. This study was based on a single dose administration of each drug. Given that these drugs are typically administered chronically, future studies should assess the effects of chronic administration.