CARN Neurobiology of Addiction 5 — Questions and Answers
Question 1: Stress-induced relapse is neurobiologically mediated primarily through which system projecting to the bed nucleus of the stria terminalis (BNST)?
- Cholinergic projections from the nucleus basalis
- CRF and noradrenergic projections from the locus coeruleus and amygdala (Correct answer)
- Serotonergic projections from the dorsal raphe
- Dopaminergic projections from the substantia nigra
Correct answer: CRF and noradrenergic projections from the locus coeruleus and amygdala
Stress-induced relapse involves CRF and noradrenergic (from locus coeruleus) inputs to the BNST and extended amygdala, activating anxiety and drug-seeking circuits.
Question 2: The 'dark side of addiction' described by Koob refers to:
- Covert drug procurement behaviors
- The negative emotional state driving drug use for relief rather than pleasure (Correct answer)
- Neurological damage visible on brain imaging
- Social isolation caused by substance use disorders
Correct answer: The negative emotional state driving drug use for relief rather than pleasure
Koob's 'dark side' describes the shift from positive reinforcement (seeking pleasure) to negative reinforcement (seeking relief from dysphoria, anxiety, and pain) as addiction progresses.
Question 3: Which receptor type mediates alcohol's positive reinforcing effects through the mesolimbic dopamine system?
- Exclusively GABA-A receptors
- Multiple systems including mu-opioid, GABA-A, and dopamine receptors acting in concert (Correct answer)
- Only NMDA glutamate receptors
- Primarily nicotinic acetylcholine receptors in isolation
Correct answer: Multiple systems including mu-opioid, GABA-A, and dopamine receptors acting in concert
Alcohol's rewarding effects involve multiple receptor systems: mu-opioid receptors trigger dopamine release, GABA-A activation produces anxiolysis and euphoria, and NMDA blockade contributes to its reinforcing profile.
Question 4: Nicotine's addictive properties are primarily mediated through its action on:
- Mu-opioid receptors in the nucleus accumbens
- Nicotinic acetylcholine receptors (nAChRs) on VTA dopamine neurons (Correct answer)
- GABA-B autoreceptors in the prefrontal cortex
- Serotonin transporters in the raphe nuclei
Correct answer: Nicotinic acetylcholine receptors (nAChRs) on VTA dopamine neurons
Nicotine directly activates alpha4beta2 nicotinic acetylcholine receptors on VTA dopamine neurons, stimulating dopamine release in the nucleus accumbens and producing reinforcement.
Question 5: Genetic heritability estimates for substance use disorders generally range from:
- 5-15%, indicating minimal genetic influence
- 40-60%, indicating substantial but not deterministic genetic contribution (Correct answer)
- 90-99%, indicating nearly complete genetic determination
- 25-30%, indicating primarily environmental causation
Correct answer: 40-60%, indicating substantial but not deterministic genetic contribution
Twin and family studies consistently estimate heritability of substance use disorders at 40-60%, indicating genes significantly influence vulnerability while environment also plays a major role.
Question 6: Downregulation of D2 dopamine receptors in the striatum, observed in addiction neuroimaging, contributes to:
- Enhanced sensitivity to natural rewards compensating for drug effects
- Blunted reward response to natural reinforcers, increasing vulnerability to drug seeking (Correct answer)
- Increased inhibitory control over impulsive behaviors
- Normalization of the dopamine system toward pre-addiction baseline
Correct answer: Blunted reward response to natural reinforcers, increasing vulnerability to drug seeking
D2 receptor downregulation reduces sensitivity to natural rewards, creating a hypodopaminergic state where only powerful drug stimuli can generate meaningful reward signals.
Question 7: The process of extinction learning in addiction treatment (such as cue exposure therapy) targets which neurobiological mechanism?
- Erasing the original drug memory engram completely
- Forming a new inhibitory memory that competes with the drug-cue association (Correct answer)
- Permanently suppressing dopamine release in the NAc
- Reversing histone acetylation in the prefrontal cortex
Correct answer: Forming a new inhibitory memory that competes with the drug-cue association
Extinction does not erase original drug-cue memories but forms new inhibitory associations in the prefrontal cortex that suppress conditioned responses — explaining why relapse remains possible.
CARN Neurobiology of Addiction 5
Stress-induced relapse is neurobiologically mediated primarily through which system projecting to the bed nucleus of the stria terminalis (BNST)?