Science: Epigenetics of "Love Factor" dopamine regulates addictive behavior.

Learn about the latest advances in neuroscience ● click the blue letter to focus on us ● opioids are addictive, but cancer patients have to take these opioids for pain relief.more than 2 million Americans rely on or abuse prescription opioid analgesics and drugs.some drug addicts also have many other mental diseases, such as schizophrenia, anxiety disorder, depression, bipolar disorder, etc.therefore, drug addiction is an important public health problem.cocain promotes dopamine neurotransmission from the ventral tegmental area (VTA) to reward related brain regions, which is essential for its addiction.the projection of VTA brain area comes from the ventricular segmental area: cellular heterogeneity, connectivityandbehaviour； doi:10.1038/nrn.2016.165 In March last year, Dr. maze Ian of Ikan Medical College in Mount Sinai published an article in the journal Nature for the first time, which revealed that the pentahydroxytryptamination of histone glutamine residues occurred at h3q5 site and belonged to monoamination modification.this modification can regulate gene expression through sulfonylation.histones that control chromatin structure and gene expression regulate addiction related behaviors.serotonin is an inhibitory neurotransmitter, and dopamine is a neurotransmitter. Dopamine is a chemical substance used to help cells transmit pulses, which are called "love factor" and "happiness factor". They belong to monoamines. As a newly discovered histone monoamination modification, whether it also occurs in dopamine and plays a role in regulating addiction behavior.on April 10, 2020, maze Ian research team published an article in the top journal science again. In their previous work, they extended pentahydroxytryptamination to dopamine modification, and further found that dopamine modification in VTA brain area regulates cocaine addiction.the researchers found that histone can be used as an endogenous substrate for dopamination. Furthermore, liquid chromatography-mass spectrometry (LC-MS) of peptides showed that the modification of dopamine occurred at h3q5 site, known as h3q5 DOP.the research team previously found that pentahydroxytryptamination can exist either as single modification h3q5ser or as double modified h3k4me3q5ser. Further experiments showed that both h3q5 DOP and h3k4me3q5 DOP were present.since there is DOPA amination modification h3q5 DOP, how does this modification change in addiction and what role does it play? The researchers found a significant decrease in h3q5 DOP in the VTA brain region of cocaine addicts after death, while there was no significant change in h3k4me3q5 DOP.they further explored the changes of h3q5 DOP in addictive behavior by using cocaine self administration model in rats.after 10 days of continuous cocaine administration, the number of times of drug touch increased significantly. At the same time, h3q5 DOP was significantly decreased in VTA brain area, but this phenomenon did not exist on the 1st and 30th day after withdrawal, which indicated that dopamine modification in VTA brain area was dependent on cocaine. so far, no studies have shown the specific role of h3q5 DOP in addiction behavior. since the expression of h3q5 DOP did not decrease after cocaine withdrawal, the decreased expression of h3q5 DOP may play a role in the process of withdrawal and relapse. therefore, the researchers constructed the virus h3.3q5a, which could significantly reduce the expression of dopamination modification. They chose to inject h3.3q5a virus into VTA brain region after 10 days of continuous cocaine training. After 30 days of withdrawal, they found that the number of drug seeking behaviors in rats was significantly reduced during 1 hour cocaine training, which indicated that the decrease of dopamination modification could be reduced during the withdrawal period Less relapse. next, we need to know why reducing dopamine modification can reduce relapse behavior. first of all, RNA sequencing of the brain region showed that the decrease of h3q5 DOP expression greatly changed the gene expression pattern related to cocaine addiction, which indicated that h3q5 DOP regulated the gene expression related to cocaine addiction from the macroscopic point of view. secondly, what effect does this modification of dopamine itself have on the activity of dopaminergic neurons. in terms of electrophysiological activities, the frequency of spontaneous action potential of dopaminergic neurons decreased after the expression of h3q5 DOP was decreased. finally, in vitro rapid scanning cyclic voltammetry (fscv) showed that the release of dopamine was significantly reduced in another NAC brain region which was highly related to reward after decreasing h3q5 DOP expression in VTA brain region. in conclusion, we found that dopamine also has a histone monoamination similar to serotonin, which can reduce cocaine relapse. this is a promising therapeutic target for drug addiction.