Abstract
Cocaine dependence involves in the brain's reward circuit as well as nucleus accumbens (NAc), a key region of the mesolimbic dopamine pathway. Many studies have documented altered expression of genes and identified transcription factor networks and epigenetic processes that are fundamental to cocaine addiction. However, all these investigations have focused on mRNA and/or miRNA, which may not reflect the involvement of small nucleolar RNAs (snoRNAs), which has been implied in a broad range of biological processes and complex diseases including brain development and neuropathologocal process. To further address the role of snoRNA in cocaine addiction, we show that repeated exposure and conditioned place preference (CPP) training to cocaine negatively regulates the expression of MBII-52 mRNA level, which is a brain-specific C/D box snoRNA, but not influences the serotonin receptor 2C (5HT2CR) mRNA level in NAc. Furthemore, we show, developing lentiviral vector (LV)-expressing MBII-52 and LV-5HT2CR for stable and regulatable MBII-52 and LV-5HT2CR expression. LV-MBII-52 and LV-5HT2CR expression in NAc attenuate cocaine induced CPP and locomotor activity. Taken together, these findings show that MBII-52 and 5HT2CR exert an inhibitory influence on the behavioral responses to cocaine exposure.
Highlights
Cocaine addiction is defined as a psychological disease that is characterized by uncontrollable, compulsive drug seeking and drug abuse, which poses negative health and social consequences [1,2]
Repeated cocaine exposure produces changes in gene expression and altered neuronal morphology within the nucleus accumbens (NAc), a brain region involved in the motivational effects of drugs abuse [3,4], and these alterations are thought to contribute to the expression of conditioned place preference (CPP) and behavioral sensitization, which have been widely used for underlying the rewarding effect of psychostimulants [5,6]
We investigated whether cocaine regulates the expression of MBII-52 in the mice NAc in vivo
Summary
Cocaine addiction is defined as a psychological disease that is characterized by uncontrollable, compulsive drug seeking and drug abuse, which poses negative health and social consequences [1,2]. Small nucleolar RNAs (snoRNAs) represent one of the most abundant noncoding RNA (ncRNA) molecules of ,60 to 300 nucleotides in length [7]. MBII-52 has been reported to exhibit an 18-nucleotide-long complementarity to an alternative exon of the serotonin receptor 2C (5HT2CR) premRNA [9]. Several groups have reported the MBII-52 involved in regulation of editing or splicing of the 5HT2CR premRNA in the Prader-Willi syndrome (PWS) [10,11]. In these studies, it has been noted that a mouse model lacking MBII-52
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