Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non‐human primate and rodent model systems, we provide evidence that brain‐derived EV (BDE) miRNA, miR‐29a‐3p (mir‐29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR‐29a levels show significant increase both with drug‐seeking and reinstatement in a rat MA self‐administration model. We also show that EV‐associated miR‐29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA‐induced inflammation and synaptodendritic damage. Furthermore, treatment with the anti‐inflammatory drug ibudilast (AV411), which is known to reduce MA relapse, decreased the expression of miR‐29a and subsequently attenuated inflammation and rescued synaptodendritic injury. Finally, using plasma from MUD subjects, we provide translational evidence that EV‐miR29a could potentially serve as a biomarker to detect neuronal damage in humans diagnosed with MA use disorder (MUD). In summary, our work suggests that EV‐associated miR‐29a‐3p plays a crucial role in MUD and might be used as a potential blood‐based biomarker for detecting chronic inflammation and synaptic damage.
Nicotine is commonly co-used with other psychostimulants. These high rates of co-use have prompted much research on the interaction of nicotine and various psychostimulant drugs. These studies range from examination of illicitly used psychostimulants such as cocaine and methamphetamine to prescription psychostimulants used in the treatment of attention deficit hyperactivity disorder such as methylphenidate (Ritalin™) and d-amphetamine (active ingredient of Adderall™). However, previous reviews largely focus on the interaction between nicotine and illicitly used psychostimulants with sparse mention of prescription psychostimulants. The currently available epidemiological and laboratory research, however, suggests high co-use between nicotine and prescription psychostimulants, and that these drugs interact to augment intake of either drug. The present review synthesizes epidemiological and experimental human and pre-clinical research assessing the behavioral and neuropharmacological interactions between nicotine and prescription psychostimulants that may contribute to high co-use between nicotine and prescription psychostimulants. Further, we discuss existing gaps in current knowledge. Nicotine has been less widely studied with alternative ADHD pharmacotherapies such as bupropion and atomoxetine, but we also discuss this research.
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