CARN Neurobiology of Addiction 4 — Questions and Answers
Question 1: Neuroimaging studies of individuals with addiction commonly show reduced glucose metabolism and blood flow in which brain region?
- Occipital cortex
- Prefrontal cortex (Correct answer)
- Primary motor cortex
- Medulla oblongata
Correct answer: Prefrontal cortex
PET and fMRI studies consistently show hypofrontality (reduced prefrontal cortex activity) in addiction, correlating with impaired inhibitory control and decision-making.
Question 2: Which stage of the addiction cycle is primarily associated with activation of the extended amygdala and CRF systems?
- Binge/intoxication
- Withdrawal/negative affect (Correct answer)
- Preoccupation/anticipation
- Initial drug experimentation
Correct answer: Withdrawal/negative affect
The withdrawal/negative affect stage involves extended amygdala and CRF system activation, producing anxiety, dysphoria, and negative emotional states that drive compulsive use.
Question 3: The role of the hippocampus in addiction is best characterized as:
- Generating the initial euphoric response to drugs
- Encoding and contextual retrieval of drug-related memories that trigger craving (Correct answer)
- Regulating respiratory depression during opioid overdose
- Controlling the autonomic symptoms of withdrawal
Correct answer: Encoding and contextual retrieval of drug-related memories that trigger craving
The hippocampus encodes episodic and contextual memories of drug use; these memories can be retrieved by environmental contexts, powerfully triggering craving and relapse.
Question 4: Brain-derived neurotrophic factor (BDNF) in the context of addiction primarily:
- Consistently protects against addiction by promoting healthy neuroplasticity
- Has complex, region-specific roles — promoting addiction in some circuits and resilience in others (Correct answer)
- Exclusively mediates tolerance to opioids
- Has no established role in addiction neurobiology
Correct answer: Has complex, region-specific roles — promoting addiction in some circuits and resilience in others
BDNF has region-specific effects: in the VTA-NAc it promotes addictive behaviors, while in the medial prefrontal cortex it may confer resilience — making its role complex.
Question 5: The concept of 'opponent process theory' as applied to addiction explains:
- Why two drugs can have additive effects when used together
- Why initial drug pleasure is followed by an opposing aversive state that grows with repeated use (Correct answer)
- How classical conditioning pairs neutral stimuli with drug effects
- The mechanism by which naloxone reverses opioid overdose
Correct answer: Why initial drug pleasure is followed by an opposing aversive state that grows with repeated use
Opponent process theory posits that the initial pleasurable 'A-process' is opposed by an aversive 'B-process' that strengthens over time, driving tolerance and withdrawal-motivated use.
Question 6: Methamphetamine's neurotoxic effects on dopaminergic neurons are primarily mediated by:
- Direct mu-opioid receptor activation causing apoptosis
- Oxidative stress and excitotoxicity from massive dopamine and glutamate release (Correct answer)
- Acetylcholine depletion in the basal forebrain
- GABA-A receptor downregulation in the striatum
Correct answer: Oxidative stress and excitotoxicity from massive dopamine and glutamate release
Methamphetamine causes massive dopamine release creating reactive oxygen species, combined with glutamate excitotoxicity, resulting in oxidative damage to dopaminergic axon terminals.
Question 7: Epigenetic mechanisms in addiction, such as histone acetylation and DNA methylation, are clinically relevant because they:
- Cause permanent, irreversible changes to the genetic code
- Alter gene expression without changing DNA sequence, potentially transmissible across generations (Correct answer)
- Only affect neuronal development before birth
- Are unique to cocaine use and do not apply to other substances
Correct answer: Alter gene expression without changing DNA sequence, potentially transmissible across generations
Epigenetic changes alter gene expression patterns in addiction-related circuits without changing DNA sequence, can persist long-term, and may contribute to intergenerational transmission of addiction vulnerability.
CARN Neurobiology of Addiction 4
Neuroimaging studies of individuals with addiction commonly show reduced glucose metabolism and blood flow in which brain region?