Not all stimulants are the same: histone acetylation and deacetylation in the cortex

BISAGNO, VERÓNICA

Little Rock

Exposición; Center for Translational Neuroscience Distinguished Lecture Series; 2019

UAMS

Dysregulation of HDACs has been proposed to modulate the establishment and maintenance of aberrant transcriptional programs and behaviors associated with cognitive dysfunctions. These mechanisms may also be pivotal for psychostimulant-induced neuroadaptations and behavioral manifestations of addiction. However, more data are needed to elucidate specific molecular targets of pro-addictive and pro-cognitive drugs because they may have a differential impact on brain functions. Methamphetamine and modafinil are psychostimulants with different addictive and cognitive profiles. Specifically, methamphetamine negatively impacts the prefrontal cortex (PFC) leading to cognitive decline and addiction, whereas modafinil enhances cognition and has a low abuse liability.  In our continued efforts to understand these molecular mechanisms, we investigated the possibility that modafinil and methamphetamine may differentially influence the acetylation status of histones 3 and 4 (H3ac and H4ac) at proximal promoters of class I, II, III and IV HDACs as well as the effect on gene expression. Our results suggest that HDAC targets linked to the effects of modafinil and methamphetamine may be related to the functional effects of these psychostimulants.