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Single Cell Measurement of Dopamine Release with Simultaneous Voltage-clamp and Amperometry
Published on: November 21, 2012
Neuronal development genes are key elements mediating the reinforcing effects of methamphetamine, amphetamine, and
Ike Dela Peña1, Se Jin Jeon, Eunyoung Lee
1Uimyung Research Institute for Neuroscience, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815, Nowon-gu, Seoul, 139-742, South Korea.
Rationale:
The molecular mechanisms underlying susceptibility to psychostimulant addiction remain unclear. Searching for commonalities in the effects of addictive drugs on brain gene expression is a prolific approach to determine transcriptional signatures influencing drug abuse.
Objective:
We explored the common transcriptional responses to the reinforcing effects of psychostimulants methamphetamine, amphetamine, and methylphenidate. We also aimed to identify transcriptional changes that may subserve abuse of these drugs.
Methods:
Genome-wide transcriptome profiling analyses were performed to identify common prefrontal cortical (PFC) and striatal gene expression profiles in drug-naïve (cohort 1) and stimulant-pretreated (cohort 2) rats, which showed a conditioned place preference to and self-administration of methamphetamine, amphetamine, and methylphenidate.
Results:
In behavioral studies, stimulant-pretreated rats showed behavioral sensitization characterized by enhanced behavioral response to the rewarding or reinforcing effects of psychostimulants. Inflammation-associated genes (e.g., Alas1, S100a8 and S100a9) were identified as the primary differentially expressed genes (DEGs) in both the PFC and the striatum of cohort 1 rats, while neuronal plasticity (Sgk1)- and brain development (e.g., Bhlhe22, Neurod1, Nr4a2, and Msx1)-associated genes comprised the major upregulated DEGs in the striatum of cohort 2 rats. Furthermore, a meta-analysis of the common striatal DEGs in this study along with morphine-regulated striatal transcriptomes in mice (National Center for Biotechnology Information-Gene Expression Omnibus Database Accession Code GSE7762) suggested similar expression profiles of genes involved in neuronal development (e.g., Bhlhe22, Nr4a2).
Conclusion:
This study provides evidence that brain development-associated genes mediate the reinforcing effects of methamphetamine, amphetamine, and methylphenidate and that these transcripts may underlie susceptibility to psychostimulant addiction.
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