Annika Vannan1, Gregory L Powell1, Michela Dell'Orco2, Melissa A Wilson3, Nora I Perrone-Bizzozero2, Janet L Neisewander4. 1. School of Life Sciences, Arizona State University, Tempe, AZ, USA. 2. Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. 3. School of Life Sciences, Arizona State University, Tempe, AZ, USA; Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA. 4. School of Life Sciences, Arizona State University, Tempe, AZ, USA. Electronic address: janet.neisewander@asu.edu.
Abstract
BACKGROUND: MicroRNAs (miRNAs) are "master post-transcriptional regulators" of gene expression. Here we investigate miRNAs involved in the incentive motivation for cocaine elicited by exposure to cocaine-associated cues. METHODS: We conducted NanoString nCounter analyses of microRNA expression in the nucleus accumbens shell of male rats that had been tested for cue reactivity in a previous study. These rats had been trained to self-administer cocaine while living in isolate housing, then during a subsequent 21-day forced abstinence period they either stayed under isolate housing or switched to environmental enrichment (EE), as this EE intervention is known to decrease cocaine seeking. This allowed us to create groups of "high" and "low" cocaine seekers using a median split of cocaine-seeking behavior. RESULTS: Differential expression analysis across high- and low-seekers identified 33 microRNAs that were differentially expressed in the nucleus accumbens shell. Predicted mRNA targets of these microRNAs are implicated in synaptic plasticity, neuronal signaling, and neuroinflammation signaling, and many are known addiction-related genes. Of the 33 differentially-expressed microRNAs, 8 were specifically downregulated in the low-seeking group and another set of 8 had expression levels that were significantly correlated with cocaine-seeking behavior. CONCLUSION: These findings not only confirm the involvement of previously identified microRNAs (e.g., miR-212, miR-495) but also reveal novel microRNAs (e.g., miR-3557, miR-377) that alter, or are altered by, processes associated with cocaine-seeking behavior. Further research examining the mechanisms involved in these microRNA changes and their effects on signaling may reveal novel therapeutic targets for attenuating drug craving.
BACKGROUND: MicroRNAs (miRNAs) are "master post-transcriptional regulators" of gene expression. Here we investigate miRNAs involved in the incentive motivation for cocaine elicited by exposure to cocaine-associated cues. METHODS: We conducted NanoString nCounter analyses of microRNA expression in the nucleus accumbens shell of male rats that had been tested for cue reactivity in a previous study. These rats had been trained to self-administer cocaine while living in isolate housing, then during a subsequent 21-day forced abstinence period they either stayed under isolate housing or switched to environmental enrichment (EE), as this EE intervention is known to decrease cocaine seeking. This allowed us to create groups of "high" and "low" cocaine seekers using a median split of cocaine-seeking behavior. RESULTS: Differential expression analysis across high- and low-seekers identified 33 microRNAs that were differentially expressed in the nucleus accumbens shell. Predicted mRNA targets of these microRNAs are implicated in synaptic plasticity, neuronal signaling, and neuroinflammation signaling, and many are known addiction-related genes. Of the 33 differentially-expressed microRNAs, 8 were specifically downregulated in the low-seeking group and another set of 8 had expression levels that were significantly correlated with cocaine-seeking behavior. CONCLUSION: These findings not only confirm the involvement of previously identified microRNAs (e.g., miR-212, miR-495) but also reveal novel microRNAs (e.g., miR-3557, miR-377) that alter, or are altered by, processes associated with cocaine-seeking behavior. Further research examining the mechanisms involved in these microRNA changes and their effects on signaling may reveal novel therapeutic targets for attenuating drug craving.
Authors: Wendy J Lynch; Alexis B Peterson; Victoria Sanchez; Jean Abel; Mark A Smith Journal: Neurosci Biobehav Rev Date: 2013-06-24 Impact factor: 8.989
Authors: Vivian Y Shin; Hongchuan Jin; Enders K O Ng; Alfred S L Cheng; Wilson W S Chong; Christine Y P Wong; Wai K Leung; Joseph J Y Sung; Kent-Man Chu Journal: Carcinogenesis Date: 2010-11-15 Impact factor: 4.944
Authors: Jonathan A Hollander; Heh-In Im; Antonio L Amelio; Jannet Kocerha; Purva Bali; Qun Lu; David Willoughby; Claes Wahlestedt; Michael D Conkright; Paul J Kenny Journal: Nature Date: 2010-07-08 Impact factor: 49.962
Authors: Gregory L Powell; Annika Vannan; Ryan M Bastle; Melissa A Wilson; Michela Dell'Orco; Nora I Perrone-Bizzozero; Janet L Neisewander Journal: Sci Rep Date: 2020-07-09 Impact factor: 4.379