Project description:Circular RNA (circRNA) has recently emerged as a novel type of endogenous non-coding RNA. It plays natural microRNA sponge effect that represses the activity of corresponding miRNAs by binding with them, thus regulating gene expression. Recent studies demonstrate that circRNAs are significantly enriched in the brain and a disproportionate fraction of them is derived from host genes that code for synaptic proteins. In addition, studies have shown that microRNAs are involved in synaptic plasticity, memory formation and cocaine addiction. However, the role of circRNAs in cocaine reward is largely unknown. This study aimed to identify the expression profile of circRNAs in the striatum of mice after cocaine self-administration by using circRNA microarray analysis.
Project description:Cocaine-dependent genome-wide effects were analyzed, total RNAs were extracted from ventral striatum tissue punches and processed for RNA-seq analyses.
Project description:Comparison of gene expression in the dorsal striatum of rats after chronic binge or acute binge cocaine injections or saline treatment
Project description:Comparison of gene expression in the dorsal striatum of rats after chronic binge or acute binge cocaine injections or saline treatment
Project description:TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in neurons in the striatum of adult Chat-EGFP/Rpl10a (DW167) mice that were administered either saline or cocaine.
Project description:Ablation of the Camk4 gene in dopaminoceptive neurons of the brain was performed using the Cre/loxP system, with the recombinase expressed from a BAC-derived Drd1a promoter. Our goal was to analyze how loss of CaMKIV will affect acitivity-regulated transcription induced by strong stimulation, i.e. cocaine. Experiment Overall Design: Animals were injected i.p. with either 25 mg/kg cocaine or saline and sacrificed after one hour by cervical dislocation. Expression profiling was performed using total RNA isolated from the striatum.
Project description:Drug addiction is a major public health issue that is characterised by continued drug use despite negative consequences. However, the molecular and cellular mechanisms that underlie this behaviour are not well understood. In this study we investigated the role of miR-137, a microRNA that has been previously shown to control the expression of genes necessary for neuronal development and synapse maturation, with common variants in the MIR137 gene linked to a higher risk of schizophrenia. Previously, we revealed that miR-137 expression in cocaine-trained animals exhibited spatial and temporal variability in the dorsal striatum (DS). Building upon this observation, we hypothesised that augmenting miR-137 function in the DS would impact drug-seeking behavior under punishment conditions by modulating molecular targets involved in synaptic plasticity. Male Sprague-Dawley rats were trained to self-administer cocaine and then randomly assigned to receive either lentiviral-mediated overexpression of hsa-miR-137 (miR-137OE) or an empty pCDH-vector (pCDH-EV) control in the dorsomedial striatum (DMS). Once stable cocaine self-administration was achieved, drug-taking was assessed under conditions in which lever presses were associated with a 0.25 probability of foot shock (0.5 mA). During five days of testing, pCDH-EV control animals showed a significant reduction in responding for cocaine, whereas miR-137OE animals displayed greater resistance to the suppression of cocaine responding across foot shock sessions compared to controls. RNA-sequencing analysis of striatal tissue from miR-137OE animals revealed significant enrichment of genes involved in synaptic plasticity and astrocyte signalling compared to control animals. Taken together, these findings provide insight into the mechanisms underlying addiction risk and and contribute to a better understanding of the neural substrates involved in these disorders.