Drug Abuse and Addiction Flashcards
Dopamine Hypothesis of cocaine reinforcement
Cocaine binds to transporter and blocks reuptake of dopamine in mesolimbocortical pathways. Potentiates dopaminergic neurotransmission and initiates the sequence of events that ultimately cause rewarding effects of the drug.
Ways in which drugs change nerve cells
Cytolasmic processes - after receptor stimulation, intracellular phosphorylation.
Alteration of gene expression - activation of transcription factors.
Epigenetic Mechanisms - Changes in gene expression through drugs and experience; methylation of DNA and histone modification by acetylation to increase/decrease availability of genes for transcription.
Dopamine Receptors
Are G protein coupled
Signal transduction mechanisms can alter gene expression!!!!
Epigenetics***
Environmental exposures or choices people make can actually “mark” or remodel the structure of DNA at the cell level or even at the level of the whole organism and change gene expression.
Mechanisms of Epigenetic Change
can be precipitated by drugs of abuse
Methylation of DNA preventing translation
Acetylation of histones that result in an opening of the chromatin so that translation is facilitated.
(Histones are the balls with tails that wrap up DNA into Chromosomes)
Treatment of Alcohol abuse
Disulfiram - creates an unpleasant reaction to alcohol consumption
Naltrexone - Opioid antagonist that can be used to manage alcohol dependence
Acamprosate (Campral) - thought to stabilize chemical imbalance in the brain seen in alcohol withdrawal
Treatment of Opiate abuse
Methadone - Strong Opioid Agonist with long duration of action with controlled supply used to titrate dependence down
Buprenorphine - Mixed Opioid Agonist-Antagonist used to manage addiction and dependence
Tobacco Treatment
Nicotine replacement patches - self explanatory
Bupropion - Antidepressant used to help quit smoking by reducing cravings
Varenicline (Chantix) - Nicotinic receptor partial agonist that can reduce cravings while not giving full effect of nicotine.
Long term effects of cocaine on D2 receptors in brain
Cocaine reduces the level of active D2 receptors due to the fact that it inhibits the reuptake of Dopamine. The brain adjusts by limiting the number of receptors that can bind to Dopamine. The levels can return to normal but not for a long time.
How are drugs powerful?
They alter signal transduction and change gene expression and protein levels at the cellular level. They override neurotransmission mechanisms which manifest into behavioral changes.
RTI-336
A a phenyltropane derivative which acts as a potent and selective dopamine reuptake inhibitor and stimulant drug that can act as a substitute medication for curbing illegal cocaine use.
Vaccine Treatment
A new approach that can prevent drugs from entering the brain.
