Metallothiol transferase FosB: Difference between revisions
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<Structure load='4NB0' size='500' frame='true' align='right' caption='Structure of FosB in Staphylococcus aureus (PDB code [[4NB0]])' scene='Insert optional scene name here' /> | <Structure load='4NB0' size='500' frame='true' align='right' caption='Structure of FosB in Staphylococcus aureus (PDB code [[4NB0]])' scene='Insert optional scene name here' /> | ||
The transcription factor, DeltaFosB, is known to be involved in some of the physiological mechanisms linked to addiction and compulsive behaviors. Levels of DeltaFosB have been shown to increase in multiple regions of the brain in response to repeated drug exposure as well as stress, certain antipsychotic or antidepressant medications, electroconvulsive seizures, and certain lesions. DeltaFosB is a truncated, highly stable splice variant of the FosB transcription factor whose expression is regulated by alternative splicing of the FosB gene. Due to this splicing, DeltaFosB is known to have a half life five times that of FosB, which is thought to be a basis for addiction. | The transcription factor, DeltaFosB, is known to be involved in some of the physiological mechanisms linked to addiction and compulsive behaviors. Levels of DeltaFosB have been shown to increase in multiple regions of the brain in response to repeated drug exposure as well as stress, certain antipsychotic or antidepressant medications, electroconvulsive seizures, and certain lesions. DeltaFosB is a truncated, highly stable splice variant of the FosB transcription factor whose expression is regulated by alternative splicing of the FosB gene. Due to this splicing, DeltaFosB is known to have a half life five times that of FosB, which is thought to be a basis for addiction <ref name ="James">PMID:25083822</ref>. | ||
'''STRUCTURE''' | '''STRUCTURE''' | ||
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'''PSYCHOLOGICAL INFLUENCES''' | '''PSYCHOLOGICAL INFLUENCES''' | ||
The regulation of gene expression is believed to be related to some of the behavioral abnormalities associated with drug dependency. Due to genetic changes that are related to chronic drug use, transcription factors have been implicated in the mechanisms of addiction <ref | The regulation of gene expression is believed to be related to some of the behavioral abnormalities associated with drug dependency. Due to genetic changes that are related to chronic drug use, transcription factors have been implicated in the mechanisms of addiction <ref name ="James"/>. Addiction is thought to develop through certain pathways in the brain following chronic drug use. These areas include the nucleus accumbens, the ventral tegmental area, and the mesolimbic/dopaminergic pathway. Studies have shown that with long term use of amphetamine, cocaine, ethanol, methamphetamine, morphine, neuroleptics, nicotine, and THC, DeltaFosB accumulates primarily in the NAc and dorsal striatum. | ||
Studies have shown that when DeltaFosB has been overexpressed in mice, drug-seeking behavior is increased. Additionally, it increases sensitivity to opioids,and causes greater dependence and tolerance to morphine. | Studies have shown that when DeltaFosB has been overexpressed in mice, drug-seeking behavior is increased. Additionally, it increases sensitivity to opioids,and causes greater dependence and tolerance to morphine. | ||
It has also been found that levels of DeltaFosB are higher when drugs are self-administered rather than experimentally injected. This implies that DeltaFosB levels may be affected by behavioral rather than purely physiological effects of the drug. | It has also been found that levels of DeltaFosB are higher when drugs are self-administered rather than experimentally injected. This implies that DeltaFosB levels may be affected by behavioral rather than purely physiological effects of the drug. | ||
