Psychostimulants are not identical pharmacological agents: distinct effects of psychostimulant drugs on the regulation of class IIa HDACs in the mouse mesocorticolimbic and striatal systems.

BISAGNO V; BERNARDI A; TORRES, OSCAR V.; SOSA MH; MUÑIZ JA; URBANO FJ; GARCIA-RILL E; CADET JL

Daegu

Congreso; International Brain Research Organization Meeting; 2019

IBRO

Methamphetamine (METH), modafinil (Mod), methylphenidate (MPH) and caffeine (Caf) are psychostimulants drugs with different addictive and cognitive profiles: while METH causes neuroplastic changes that leads to cognitive deficits and addiction; modafinil, caffeine and methylphenidate can act as cognitive enhancers that improve mesocorticolimbic system function.?Epigenetic mechanisms are contributory factors in drug-induced neuroadaptations, specifically, dysregulation of histone deacetylases (HDACs) has been proposed as a potential contributor to the establishment and maintenance of aberrant transcriptional programs associated with changes in cognitive functions and behaviors.?HDACs are key players that regulate chromatin functions that generate short-term and long-term metaplastic cellular changes responsible for behavioral adaptations. We are interested in class IIa HDACs because they are most highly expressed in brain regions linked to learning and memory and also because they can shuttle between nucleus and cytoplasm.?Class IIa HDACs have several druggable targets. HDAC7 has been linked to inflammation and neuroprotection, these functions are also affected by psychostimulant exposure.