Drugs of Abuse

Define dependence in pharmacology.

Physical adaptation with tolerance and withdrawal after repeated exposure

Define addiction in pharmacology.

Compulsive drug use despite harmful consequences driven by craving

Which neurotransmitter is central to reinforcement in addiction?

Dopamine

Which pathway is primarily targeted by addictive drugs?

Mesolimbic dopamine pathway

Where do dopamine neurons of reward pathway originate?

Ventral tegmental area (VTA)

Which brain region is key for reward and reinforcement?

Nucleus accumbens

What firing pattern increases dopamine release in addiction?

Burst firing of VTA neurons

What does dopamine encode in addiction models?

Prediction error between expected and actual reward

What happens to dopamine firing when reward is omitted?

Decreases

Which transporter is critical in cocaine addiction?

Dopamine transporter (DAT)

Why don’t SSRIs cause addiction?

They do not significantly increase dopamine

Which drugs increase dopamine via reuptake inhibition?

Cocaine and amphetamines

Which drugs increase dopamine via disinhibition of GABA neurons?

Opioids and cannabinoids

What intracellular change mediates opioid withdrawal?

Increased cAMP via adenylyl cyclase upregulation

Which protein is activated during withdrawal adaptation?

CREB

Which receptor is essential for opioid dependence?

Mu-opioid receptor

What is tolerance?

Need for higher doses to achieve same effect

What are the two types of tolerance?

Pharmacokinetic and pharmacodynamic

What protein mediates receptor internalization in tolerance?

Beta-arrestin

What is unique about morphine regarding receptor internalization?

Does not promote internalization

Which region shows highest dopamine increase in addiction?

Dorsomedial shell of nucleus accumbens

What triggers relapse in addiction?

Stress, drug re-exposure, and contextual cues

What brain process underlies cue-induced craving?

Synaptic plasticity

Which type of plasticity strengthens synapses?

Long-term potentiation (LTP)

Which type weakens synapses?

Long-term depression (LTD)

Which receptor is required for LTP and LTD?

NMDA receptor

What blocks NMDA receptors at rest?

Magnesium ions

What makes NMDA receptors coincidence detectors?

Need for glutamate and depolarization

Which receptor subtype promotes LTP in addiction?

D1 receptor

What happens to dopamine neuron excitability after drug exposure?

It increases

Which neurotransmitter system is altered by hallucinogens like LSD?

Serotonin system

Which receptor does LSD activate?

5-HT2A receptor

Which drug is a nicotinic receptor agonist?

Nicotine

Which nicotinic receptor subtype mediates reward?

Alpha4beta2

Which receptor subtype contributes to nicotine reinforcement?

Alpha7

What is the main withdrawal symptom of nicotine?

Irritability

Which drug is used as partial agonist for nicotine cessation?

Varenicline

Which antidepressant is used for nicotine cessation?

Bupropion

Which drug blocks voltage-gated sodium channels and DAT?

Cocaine

What is crack cocaine?

Free base form of cocaine that is smoked

What are major risks of cocaine use?

Stroke, MI, seizures

What is reverse tolerance in cocaine?

Increased sensitivity to small doses

Which drugs reverse monoamine transporters?

Amphetamines

What transporter is disrupted by amphetamines inside neurons?

VMAT

What is the effect of amphetamines on dopamine release?

Nonvesicular release into synapse

Which neurotransmitter is most affected by MDMA?

Serotonin

What major toxicity is associated with MDMA?

Hyperthermia

What dangerous condition can result from excessive water intake in MDMA users?

Hyponatremia

Which opioid receptor inhibits GABA neurons?

Mu receptor

Which opioid receptor inhibits dopamine neurons?

Kappa receptor

Which opioid is 100 times more potent than morphine?

Fentanyl

What is the antidote for opioid overdose?

Naloxone

What is a limitation of naloxone?

Short half-life

What is substitution therapy for opioids?

Replacing short-acting opioid with long-acting one

Which drug is used for opioid substitution therapy?

Methadone

Which partial agonist is used for opioid addiction?

Buprenorphine

What is the mechanism of cannabinoids?

Retrograde inhibition of neurotransmitter release

Which receptor mediates cannabinoid effects?

CB1 receptor

What is the active compound in marijuana?

THC

What is a major cognitive effect of cannabis?

Memory impairment

What is the relative addiction risk of cannabis?

2 out of 5

What is GHB?

GABA metabolite acting on GABA_B receptors

What effect does GHB have at low doses?

Disinhibition of dopamine neurons

What effect occurs at high doses of GHB?

Inhibition of dopamine release

What is a major abuse risk of GHB?

Used as date rape drug

What is the mechanism of benzodiazepines?

Enhance GABA_A receptor activity

Which subunit is linked to addiction in benzodiazepines?

Alpha1

Which receptor subtype mediates alcohol effects?

Multiple including GABA_A and NMDA

What is delirium tremens?

Severe alcohol withdrawal with hallucinations and autonomic instability

Which drugs treat alcohol withdrawal?

Benzodiazepines

What is the mechanism of inhalants?

Alter ion channels in CNS

Which inhalant increases VTA excitability?

Toluene

Which inhalant is not addictive?

Amyl nitrite

What is the mechanism of ketamine?

NMDA receptor antagonist

Why does ketamine have rapid antidepressant effects?

Enhances AMPA signaling

What is esketamine?

S-enantiomer of ketamine

Which therapy targets nucleus accumbens in addiction?

Deep brain stimulation

Which therapy targets prefrontal cortex?

Transcranial magnetic stimulation

Define dependence in pharmacology.

Physical adaptation with tolerance and withdrawal after repeated exposure

Define addiction in pharmacology.

Compulsive drug use despite harmful consequences driven by craving

Which neurotransmitter is central to reinforcement in addiction?

Dopamine

Which pathway is primarily targeted by addictive drugs?

Mesolimbic dopamine pathway

Where do dopamine neurons of reward pathway originate?

Ventral tegmental area (VTA)

Which brain region is key for reward and reinforcement?

Nucleus accumbens

What firing pattern increases dopamine release in addiction?

Burst firing of VTA neurons

What does dopamine encode in addiction models?

Prediction error between expected and actual reward

What happens to dopamine firing when reward is omitted?

Decreases

Which transporter is critical in cocaine addiction?

Dopamine transporter (DAT)

Why don’t SSRIs cause addiction?

They do not significantly increase dopamine

Which drugs increase dopamine via reuptake inhibition?

Cocaine and amphetamines

Which drugs increase dopamine via disinhibition of GABA neurons?

Opioids and cannabinoids

What intracellular change mediates opioid withdrawal?

Increased cAMP via adenylyl cyclase upregulation

Which protein is activated during withdrawal adaptation?

CREB

Which receptor is essential for opioid dependence?

Mu-opioid receptor

What is tolerance?

Need for higher doses to achieve same effect

What are the two types of tolerance?

Pharmacokinetic and pharmacodynamic

What protein mediates receptor internalization in tolerance?

Beta-arrestin

What is unique about morphine regarding receptor internalization?

Does not promote internalization

Which region shows highest dopamine increase in addiction?

Dorsomedial shell of nucleus accumbens

What triggers relapse in addiction?

Stress, drug re-exposure, and contextual cues