Neurobiology of Addiction Flashcards

Accumulation of delta FosB (ΔFosB) in the nucleus accumbens with repeated drug exposure is significant because it:

Answer: Represents a stable molecular switch contributing to long-lasting addiction-related neuroplasticity

ΔFosB is a uniquely stable transcription factor that accumulates with repeated drug exposure and persists weeks to months, altering gene expression in ways that reinforce addictive behaviors.

Koob and Volkow's 'three-stage cycle of addiction' includes which of the following stages?

Answer: Intoxication/binge, withdrawal/negative affect, preoccupation/anticipation (craving)

The three-stage model describes binge/intoxication (basal ganglia), withdrawal/negative affect (extended amygdala), and preoccupation/anticipation (prefrontal cortex) — each stage engages distinct brain circuits.

Behavioral sensitization (reverse tolerance) — where repeated drug exposure produces increasingly exaggerated responses — is most prominently associated with which system?

Answer: The mesolimbic dopamine system and stimulant drugs

Behavioral sensitization is classically demonstrated with stimulants (cocaine, amphetamines) via sensitization of mesolimbic dopamine circuits, producing enhanced locomotor and reinforcing responses.

Alcohol's acute anxiolytic and sedative effects are primarily mediated through which mechanism?

Answer: Blocking NMDA glutamate receptors and potentiating GABA-A receptor function

Alcohol potentiates GABA-A receptors (enhancing inhibition) and inhibits NMDA glutamate receptors (reducing excitation), producing CNS depression, anxiolysis, and sedation.

The insula cortex plays which specific role in addiction that makes it a therapeutic target?

Answer: Processing interoceptive signals (body states) that drive drug urges and conscious craving

The insula integrates interoceptive body signals with conscious awareness; disruption of insula function (e.g., in stroke patients) has been shown to eliminate cigarette craving, implicating it in conscious drug urges.

Opioid-induced hyperalgesia (OIH) following long-term opioid use is primarily mediated by:

Answer: NMDA receptor sensitization and increased dynorphin/kappa-opioid signaling

OIH involves NMDA receptor-mediated central sensitization and upregulation of pronociceptive kappa-opioid/dynorphin signaling, paradoxically increasing pain sensitivity with chronic opioid use.

The ALDH2*2 variant (aldehyde dehydrogenase 2 deficiency), common in East Asian populations, affects alcohol use disorder risk primarily by:

Answer: Causing accumulation of acetaldehyde, producing flushing and aversion that is protective against AUD

ALDH2*2 impairs acetaldehyde metabolism, causing toxic acetaldehyde buildup after drinking (flushing, nausea, tachycardia), which acts as a biological deterrent — the same mechanism exploited by disulfiram.