page_title: TET enzymes
section_title: Addiction
hierarchical_section_title: TET enzymes / TET functions / Addiction
caption_attribution_description: English: Important structures relatedto addiction
context_page_description: The TET enzymes are a family of ten-eleven translocation methylcytosine dioxygenases. They are instrumental in DNA demethylation. 5-Methylcytosine is a methylated form of the DNA base cytosine that often regulates gene transcription and has several other functions in the genome.
  Demethylation by TET enzymes, can alter the regulation of transcription. The TET enzymes catalyze the hydroxylation of DNA 5-methylcytosine to 5-hydroxymethylcytosine, and can further catalyse oxidation of 5hmC to 5-formylcytosine and then to 5-carboxycytosine. 5fC and 5caC can be removed from the DNA base sequence by base excision repair and replaced by cytosine in the base sequence.
  TET enzymes have central roles in DNA demethylation required during embryogenesis, gametogenesis, memory, learning, addiction and pain perception.
context_section_description: The nucleus accumbens (NAc) has a significant role in addiction.  In the nucleus accumbens of mice, repeated cocaine exposure resulted in reduced TET1 messenger RNA (mRNA) and reduced TET1 protein expression. Similarly, there was a ~40% decrease in TET1 mRNA in the NAc of human cocaine addicts examined postmortem.
  As indicated above in learning and memory, a short hairpin RNA (shRNA) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference.  Feng et al. injected shRNA targeted to TET1 in the NAc of mice.  This could reduce TET1 expression in the same manner as reduction of TET1 expression with cocaine exposure.  They then used an indirect measure of addiction, conditioned place preference.  Conditioned place preference can measure the amount of time an animal spends in an area that has been associated with cocaine exposure, and this can indicate an addiction to cocaine.   Reduced Tet1 expression caused by shRNA injected into the NAc robustly enhanced cocaine place conditioning.
caption: . Brain structures connected to addiction
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