ADM Neurobiology of Addiction 2 — Questions and Answers
Question 1: Imbalance between GABA (inhibitory) and glutamate (excitatory) systems is most clinically critical during withdrawal from which substance?
- Cannabis
- Alcohol (Correct answer)
- Cocaine
- Opioids
Correct answer: Alcohol
Chronic alcohol use suppresses glutamate and enhances GABA; abrupt cessation leads to glutamate rebound and GABA deficit, causing potentially fatal withdrawal seizures.
Question 2: Solomon and Corbit's 'opponent process theory' of addiction describes addiction as:
- A purely genetic predisposition to substance seeking
- An initial pleasurable A-state followed by an aversive B-state that strengthens with repeated use (Correct answer)
- A conditioned response to environmental cues alone
- A disorder of impaired serotonin synthesis
Correct answer: An initial pleasurable A-state followed by an aversive B-state that strengthens with repeated use
The opponent process theory posits that the hedonic A-state (pleasure) weakens while the opponent B-state (dysphoria/withdrawal) strengthens, driving continued use to avoid the negative state.
Question 3: The corticotropin-releasing factor (CRF) system activated during withdrawal contributes primarily to:
- Enhanced reward sensitivity
- Negative affect and anxiety driving relapse (Correct answer)
- Improved cognitive flexibility
- Reduced drug craving
Correct answer: Negative affect and anxiety driving relapse
CRF release during withdrawal activates stress circuits in the extended amygdala, producing negative emotional states (anxiety, dysphoria) that motivate drug use to relieve distress.
Question 4: Berridge and Robinson's 'incentive salience theory' distinguishes between 'wanting' and 'liking' in addiction, proposing that compulsive drug-seeking is driven by:
- Enhanced 'liking' (pleasure) with each use
- Sensitized 'wanting' (motivation) even as 'liking' decreases (Correct answer)
- Equal increases in both wanting and liking
- Decreased wanting due to prefrontal hyperactivity
Correct answer: Sensitized 'wanting' (motivation) even as 'liking' decreases
Incentive salience theory holds that dopamine sensitization amplifies 'wanting' (motivation circuits) independently of 'liking' (hedonic circuits), explaining compulsive use despite reduced pleasure.
Question 5: Chronic opioid exposure leads to upregulation of which intracellular signaling pathway, contributing to dependence?
- PI3K/Akt pathway
- cAMP/PKA pathway (adenylyl cyclase superactivation) (Correct answer)
- JAK/STAT pathway
- Wnt/beta-catenin pathway
Correct answer: cAMP/PKA pathway (adenylyl cyclase superactivation)
Opioids acutely inhibit adenylyl cyclase; chronic exposure causes compensatory superactivation of the cAMP/PKA pathway, which manifests as withdrawal when opioids are removed.
Question 6: PET and fMRI studies consistently show which finding across most substance use disorders?
- Increased prefrontal cortex glucose metabolism
- Reduced dopamine D2 receptor availability in the striatum (Correct answer)
- Enlarged nucleus accumbens volume
- Increased serotonin transporter density
Correct answer: Reduced dopamine D2 receptor availability in the striatum
Neuroimaging studies consistently demonstrate reduced striatal dopamine D2 receptor availability in individuals with substance use disorders, reflecting dopamine system dysregulation.
Question 7: The 'kindling' phenomenon in addiction is most clinically relevant to which condition?
- Opioid tolerance development
- Alcohol withdrawal seizures becoming more severe with each detoxification (Correct answer)
- Cannabis-induced psychosis
- Stimulant-induced cardiovascular complications
Correct answer: Alcohol withdrawal seizures becoming more severe with each detoxification
Kindling refers to the progressive worsening of alcohol withdrawal with repeated detoxifications, where each withdrawal episode lowers the seizure threshold through glutamate sensitization.
ADM Neurobiology of Addiction 2
Imbalance between GABA (inhibitory) and glutamate (excitatory) systems is most clinically critical during withdrawal from which substance?