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The molecular biology of addictive drugs
1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Abstract:
The additive drugs alcohol, morphine, cocaine, and amphetamine are each associated with the development of tolerance and physical dependence. Changes in gene expression occur in cell culture and in vivo with the administration of these centrally-acting drugs. This article reviews those experiments that have studied drug-induced alterations in gene transcription. Ethanol has diverse effects on the amounts of messenger RNA molecules within the central nervous system. Ion channels, neuropeptides, membrane receptors, and immediate early genes represent several regulated mRNAs. The effects are selective, however, as many other specific products are not altered. Evidence for a genetic predisposition to ethanol use reinforces the importance of the genotype. Opioids, cocaine, and amphetamine also affect gene transcription. Messenger RNAs studied have included many of those demonstrated to be altered by alcohol use. Interestingly, use of any of these drugs alters the expression of immediate early genes. These genes may represent an initial step in the pathway that leads to drug addiction. The composite of drug-induced changes in gene expression results in the cellular responses of tolerance and dependence. The characterization of these changes should provide a better understanding of the molecular mechanisms of drug addiction.
Insights
Additive drugs like alcohol, morphine, cocaine, and amphetamine alter gene expression, leading to tolerance and dependence. Understanding these gene transcription changes is key to the molecular mechanisms of drug addiction.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Additive drugs, including alcohol, morphine, cocaine, and amphetamine, are known to cause tolerance and physical dependence.
- Administration of these centrally-acting drugs induces changes in gene expression in both cell culture and in vivo.
- Genetic predisposition plays a role in the susceptibility to drug use, highlighting the importance of genotype.
Purpose of the Study:
- To review experiments investigating drug-induced alterations in gene transcription.
- To explore the impact of various addictive drugs on gene expression within the central nervous system.
- To understand the molecular mechanisms underlying drug addiction through gene expression changes.
Main Methods:
- Review of experimental studies on drug-induced alterations in gene transcription.
- Analysis of changes in messenger RNA (mRNA) levels in the central nervous system following drug administration.
- Focus on specific regulated mRNAs, including those for ion channels, neuropeptides, membrane receptors, and immediate early genes.
Main Results:
- Ethanol selectively affects mRNA levels in the central nervous system, altering specific gene products.
- Opioids, cocaine, and amphetamine also impact gene transcription, affecting many of the same mRNAs as alcohol.
- All studied drugs alter the expression of immediate early genes, suggesting a potential initial step in addiction pathways.
Conclusions:
- Drug-induced changes in gene expression contribute to cellular responses of tolerance and dependence.
- Immediate early genes may play a crucial role in the initial stages of the addiction process.
- Characterizing these gene expression alterations offers insights into the molecular mechanisms of drug addiction.