Neurotransmitter System In Addiction Flashcards
What is drug addiction?
Drug addiction, also known as substance use disorder (SUD), is a complex condition characterized by compulsive drug-seeking, continued use despite harmful consequences, and neuroadaptive changes in the brain’s reward circuitry.
Several mechanisms contribute to the development and maintenance of drug addiction
Increased risk for relapse despite years of abstinence
Differentiate between tolerance, sensitization and dependence
Tolerance – reduced drug effect after repeated use.
Sensitization – increased drug effect after repeated use.
Dependence – altered physiological state that leads to withdrawal symptoms upon cessation of drug use
Differentiate between reward and reinforcement in addiction
Reward – Positive emotional effects.
Reinforcement – A stimulus that causes a response to be maintained and increased.
Positive reinforcement: increases behavioral response to get a positive reward (food, sex, etc.). Negative reinforcement: increases behavioral response to end punishment (pain, starvation).
In this way, rewards and reinforcements in the environment powerfully shape an individual’s behavior.
How is the reward pathway activated in addiction?
Many drugs of abuse activate the brain’s reward pathway, particularly the mesolimbic dopamine system.
Dopamine is a neurotransmitter involved in pleasure, reward, and reinforcement learning.
Drugs such as cocaine, amphetamines, opioids, and alcohol increase dopamine levels in the nucleus accumbens, a key brain region involved in reward processing.
This dopamine surge leads to feelings of euphoria and reinforces drug-seeking behaviors
What effect does addiction have on neuroplasticity and learning?
Chronic drug use induces neuroplasticity changes in the brain, altering the structure and function of neurons and synapses.
These changes can lead to the formation of drug-related memories and associations, contributing to the conditioning of drug-seeking behaviors.
Neurotransmitter systems involved in learning and memory, such as glutamate and the endogenous opioid system, play crucial roles in the neuroplasticity underlying addiction.
Describe the relationship between addiction, tolerance and dependence
With repeated drug exposure, tolerance may develop, requiring higher doses to achieve the same effects.
Dependence may also occur, characterized by physical and psychological withdrawal symptoms upon cessation of drug use.
Tolerance and dependence result from neuroadaptive changes in neurotransmitter systems, receptor downregulation, and alterations in neuronal excitability
How do stress and craving contribute to addiction?
Stressful life events, environmental cues, and drug-associated stimuli can trigger intense cravings for drugs, contributing to relapse and continued drug use.
Stress activates the hypothalamic-pituitary-adrenal (HPA) axis and releases stress hormones such as cortisol, which can modulate neurotransmitter systems involved in addiction, including dopamine, serotonin, and GABA
How do genetic and environmental factors contribute to addiction?
Genetic factors account for approximately 40-60% of the risk of developing addiction.
Variations in genes encoding neurotransmitter receptors, enzymes involved in drug metabolism, and signaling molecules can influence susceptibility to addiction.
Environmental factors, such as exposure to drugs during adolescence, peer pressure, trauma, and socioeconomic status, also play significant roles in addiction risk.
How do co-occurring mental health disorders contribute to addiction?
Substance use disorders commonly co-occur with other mental health conditions, such as depression, anxiety, and post-traumatic stress disorder (PTSD).
These comorbidities may contribute to the initiation and maintenance of drug use and complicate addiction treatment
How does addiction affect decision making and executive function?
Chronic drug use can impair cognitive functions such as decision-making, impulse control, and judgment, leading to maladaptive behaviors and continued drug-seeking despite negative consequences.
Dysfunction in prefrontal cortical regions involved in executive function may contribute to impulsivity and poor decision-making in individuals with addiction
Which drugs block the dopamine pump?
Cocaine
Amphetamine
Which drugs mimic neurotransmitters by activating receptors?
Morphine & other opiates
Nicotine
Marijuana
Which drugs activate or inhibit channels?
Alcohol
PCP, ketamine
What is the MoA of stimulant drugs?
Stimulants such as cocaine and amphetamines increase dopamine, norepinephrine, and serotonin levels, leading to increased alertness, euphoria, and heightened arousal
What is the MoA of depressants?
Depressants such as alcohol, benzodiazepines, and opioids enhance the inhibitory effects of gamma-aminobutyric acid (GABA) or inhibit the excitatory effects of glutamate, resulting in sedation, relaxation, and decreased anxiety
What is the MoA of hallucinogens?
Hallucinogens such as LSD and psilocybin alter perception, mood, and cognition by interacting with serotonin receptors and other neurotransmitter systems
What is the general treatment approach to addiction?
Understanding the pharmacology of drug substance abuse is essential for developing effective treatment strategies.
Pharmacological interventions, such as medications for opioid addiction (e.g., methadone, buprenorphine) or alcohol dependence (e.g., naltrexone, acamprosate), target specific neurotransmitter systems to reduce cravings, withdrawal symptoms, and relapse risk.
Behavioral therapies, counseling, and support programs are also important components of addiction treatment
Describe the pharmacodynamics of nicotine
Absorption is pH dependent
In acidic media
Ionized poorly absorbed across membranes
In alkaline media
Nonionized well absorbed across membranes
At physiologic pH (7.4), ~31% of nicotine is nonionized
List nicotine’s withdrawal effects
Irritability/frustration/anger
Anxiety
Difficulty concentrating
Restlessness/impatience
Depressed mood/depression
Insomnia
Impaired performance
Increased appetite/weight gain
Cravings
What is the MoA of nicotine?
Nicotine primarily exerts its effects by binding to and activating nicotinic acetylcholine receptors (nAChRs) in the central nervous system and peripheral tissues.
Activation of nAChRs leads to the release of neurotransmitters such as dopamine, norepinephrine, serotonin, and glutamate
What are the effects of nicotine?
Enhanced mood
Increased alertness and arousal
Improved cognitive function
Appetite suppression
How does nicotine activate the reward pathway?
Nicotine’s activation of nAChRs in the mesolimbic dopamine system, particularly in the ventral tegmental area (VTA) and nucleus accumbens, leads to the release of dopamine, a neurotransmitter associated with pleasure and reward.
This activation reinforces the desire to use nicotine, contributing to its addictive properties
Describe tolerance and dependence of nicotine
With chronic nicotine use, tolerance can develop, requiring higher doses to achieve the same effects.
Dependence may also develop, characterized by withdrawal symptoms upon cessation of nicotine intake.
Nicotine withdrawal symptoms include irritability, anxiety, depressed mood, difficulty concentrating, increased appetite, and cravings for nicotine
Explain the pharmacokinetics of nicotine
Nicotine is rapidly absorbed through mucous membranes in the mouth and lungs when tobacco products are smoked or chewed.
It reaches peak blood levels within minutes, producing rapid effects. Nicotine is metabolized primarily in the liver by the enzyme cytochrome P450 2A6 (CYP2A6) into inactive metabolites, which are then eliminated in the urine
What is the MoA of alcohol?
Alcohol primarily acts as a central nervous system depressant, enhancing the inhibitory effects of the neurotransmitter gamma-aminobutyric acid (GABA) and inhibiting the excitatory effects of glutamate
What are the effects of alcohol?
Sedation and relaxation
Decreased anxiety and inhibitions
Impaired judgment, coordination, and reaction time
How does alcohol activate the reward pathway?
Alcohol consumption leads to the release of dopamine in the brain’s reward pathway, particularly in the nucleus accumbens, reinforcing the pleasurable effects of alcohol and contributing to its addictive potential
Describe tolerance and dependence of alcohol
With repeated alcohol exposure, tolerance can develop, necessitating higher doses to achieve the desired effects.
Dependence may also develop, characterized by physical and psychological withdrawal symptoms upon cessation of alcohol intake.
Alcohol withdrawal symptoms include tremors, anxiety, sweating, nausea, insomnia, and in severe cases, seizures and delirium tremens
Explain the pharmacokinetics of alcohol
Alcohol is rapidly absorbed through the stomach and small intestine and enters the bloodstream, reaching peak blood alcohol concentration (BAC) within 30 to 90 minutes, depending on factors such as the rate of consumption and presence of food in the stomach.
Alcohol is metabolized primarily in the liver by alcohol dehydrogenase (ADH) and other enzymes into acetaldehyde, which is further metabolized into acetate by aldehyde dehydrogenase (ALDH).
These metabolites are eventually converted into carbon dioxide and water and eliminated from the body via urine and exhalation
List the drugs used in the management of alcohol abuse
Disulfiram
Naltrexone
Acamprosate
What is the MoA of disulfiram?
Disulfiram- This drug blocks the oxidation of acetaldehyde to acetic acid by inhibiting aldehyde dehydrogenase. This results in the accumulation of acetaldehyde in the blood, causing flushing, tachycardia, hyperventilation, and nausea. Disulfiram has found some use in patients seriously desiring to stop alcohol ingestion.
What is the MoA of naltrexone?
Naltrexone- is a competitive and relatively long-acting opioid antagonist that helps decrease cravings for alcohol
What is the MoA of acamprosate?
Acamprosate- This drug is an agent used in alcohol dependence treatment programs and is thought to decrease cravings through its regulatory effects on N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation. This agent should also be used in conjunction with supportive psychotherapy
Describe the treatment approach in opioid agonist maintenance therapy
Methadone: Methadone is a long-acting opioid agonist that helps prevent withdrawal symptoms and reduce cravings in individuals with opioid dependence. It is typically administered in a supervised clinic setting daily.
Buprenorphine: Buprenorphine is a partial opioid agonist that can be prescribed by qualified healthcare providers in office-based settings. It reduces opioid cravings and withdrawal symptoms while having a lower risk of respiratory depression and overdose compared to full opioid agonists like methadone.
Naltrexone: Naltrexone is an opioid antagonist that blocks the effects of opioids by binding to opioid receptors. It can help prevent relapse in individuals who have already undergone detoxification and are abstinent from opioids.
What is nicotine replacement therapy?
Nicotine Patch, Gum, Lozenge, Inhaler, Nasal Spray: NRT provides a controlled dose of nicotine to help reduce cravings and withdrawal symptoms in individuals trying to quit smoking.
It is available over-the-counter and by prescription
Which medications are used in stimulant use disorder?
Bupropion: Bupropion is an antidepressant that may help reduce cravings and withdrawal symptoms in individuals with stimulant use disorder. Its precise mechanism of action in treating SUDs is not fully understood.
Modafinil: Modafinil is a wakefulness-promoting agent that has shown some efficacy in reducing cocaine cravings and improving cognitive function in individuals with cocaine use disorder.
Which adjunctive medications are used to treat substance use disorders?
Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants may be prescribed to manage co-occurring mood disorders and reduce symptoms of depression and anxiety in individuals with substance use disorders.
Anticonvulsants: Certain anticonvulsant medications, such as gabapentin and topiramate, have shown promise in reducing cravings and promoting abstinence in individuals with alcohol and substance use disorders.
