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ABPN Addiction Psychiatry study materials
ABPN Addiction Psychiatry study resources

ABPN Addiction Psychiatry practice questions

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Question 1Neurobiology, Etiology, and Pharmacology of Addictive Disorders

The mesolimbic dopamine pathway arises from which pair of structures?

  1. Locus coeruleus to prefrontal cortex
  2. Raphe nuclei to amygdala
  3. Ventral tegmental area to nucleus accumbens Correct answer.
  4. Substantia nigra to dorsal striatum

Explanation

The mesolimbic pathway projects from ventral tegmental area dopamine neurons to limbic targets including the nucleus accumbens, and it is central to reward and reinforcement. The other pathways listed are nigrostriatal, noradrenergic, and serotonergic circuits with different functions.

Question 2Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Alcohol withdrawal seizures are most directly explained by which neuroadaptive change?

  1. Reduced GABA-A inhibition and NMDA receptor rebound hyperexcitability Correct answer.
  2. Cholinergic overactivity in the basal forebrain
  3. Opioid receptor blockade in the locus coeruleus
  4. Excess dopamine D2 receptor stimulation

Explanation

Chronic alcohol enhances GABA-A inhibition and suppresses NMDA receptor function. Abrupt removal produces reduced GABAergic inhibition and rebound glutamatergic excitation, which lowers seizure threshold.

Question 3Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Cocaine increases synaptic dopamine primarily by which mechanism?

  1. Inhibiting monoamine oxidase intracellularly
  2. Directly activating dopamine D2 receptors
  3. Reversing vesicular monoamine transport to release dopamine
  4. Blocking the dopamine transporter and reducing dopamine reuptake Correct answer.

Explanation

Cocaine binds the dopamine transporter and prevents reuptake, increasing extracellular dopamine. Amphetamine also reverses vesicular transport, and direct D2 agonism is not cocaine's main action.

Question 4Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Which opioid receptor is the primary target for morphine analgesia and reward?

  1. Delta
  2. Mu Correct answer.
  3. Sigma
  4. Kappa

Explanation

Mu-opioid receptors mediate analgesia, euphoria, respiratory depression, and physical dependence. Kappa and delta receptors modulate other opioid effects, and sigma is not an opioid receptor.

Question 5Neurobiology, Etiology, and Pharmacology of Addictive Disorders

A twin study reports that alcohol use disorder has a heritability of about 0.50. Which interpretation is most appropriate?

  1. About half of the variance in liability in the studied population is attributable to genetic differences Correct answer.
  2. Half of affected individuals inherited the disorder from an affected parent
  3. The disorder is caused equally by one gene and one environmental exposure
  4. An individual with an affected twin has a 50% lifetime risk

Explanation

Heritability estimates the proportion of population variance in a trait attributable to genetic differences under the study conditions. It does not describe an individual's risk or identify a specific gene.

Question 6Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Repeated intermittent psychostimulant exposure can produce which persistent change?

  1. Immediate loss of dopamine neurons
  2. Reversal of drug effects by conditioned cues
  3. Progressive decrease in locomotor response
  4. Progressive increase in drug-induced locomotor and reward responses Correct answer.

Explanation

Sensitization is a progressive increase in behavioral and reward responses after repeated intermittent drug administration. It reflects enduring neuroadaptation and is distinct from tolerance.

Question 7Neurobiology, Etiology, and Pharmacology of Addictive Disorders

An individual in recovery experiences intense craving when passing a former drinking bar. This is best explained by which process?

  1. GABA receptor sensitization
  2. Operant extinction
  3. Negative reinforcement
  4. Classical conditioning of environmental cues to drug effects Correct answer.

Explanation

Environmental cues repeatedly paired with drug effects can become conditioned stimuli that elicit craving and drug-seeking responses. This cue reactivity is a form of classical conditioning.

Question 8Neurobiology, Etiology, and Pharmacology of Addictive Disorders

In addiction, allostasis is best described as which process?

  1. An acute withdrawal response limited to the elimination half-life of the drug
  2. A shift in reward and stress set points with escalating drug use Correct answer.
  3. A conditioned placebo response elicited by previously neutral environmental cues
  4. A stable reward set point maintained by unchanged homeostatic feedback mechanisms

Explanation

Allostasis refers to adaptation of reward and stress systems away from their original set points. As these systems become dysregulated, more drug is needed to maintain equilibrium and normal function.

Question 9Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Nicotine's primary reinforcing action is mediated by which receptor effect?

  1. Direct antagonism of mu-opioid receptors in the brainstem
  2. Alpha4beta2 nicotinic receptor activation on VTA dopamine neurons Correct answer.
  3. Blockade of dopamine transporters in the nucleus accumbens
  4. Inhibition of GABA-A receptors in the cerebral cortex

Explanation

Nicotine activates alpha4beta2 nicotinic acetylcholine receptors on ventral tegmental area dopamine neurons, increasing dopamine release in the nucleus accumbens. This action is central to nicotine reinforcement.

Question 10Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Benzodiazepines potentiate GABA-A currents mainly by which mechanism?

  1. Increasing the duration of channel openings
  2. Reducing chloride conductance
  3. Increasing the frequency of channel openings Correct answer.
  4. Directly opening GABA-A channels without GABA

Explanation

Benzodiazepines are positive allosteric modulators that increase the frequency of GABA-A channel openings in the presence of GABA. Barbiturates more characteristically increase channel opening duration.

Question 11Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Naltrexone reduces alcohol reinforcement primarily by which action?

  1. Irreversible inhibition of aldehyde dehydrogenase causing acetaldehyde accumulation
  2. Competitive blockade of NMDA glutamate receptors
  3. Mu-opioid antagonism blunting alcohol-induced dopamine release Correct answer.
  4. Positive allosteric modulation of GABA-A receptors

Explanation

Naltrexone antagonizes mu-opioid receptors, which blunts opioid-mediated reinforcement and alcohol-induced dopamine release. This can reduce heavy drinking and craving.

Question 12Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Acamprosate's action in alcohol use disorder is thought to involve which effect?

  1. GABA-A positive allosteric modulation
  2. Modulation of glutamatergic NMDA receptor activity Correct answer.
  3. Mu-opioid receptor antagonism
  4. Inhibition of acetaldehyde dehydrogenase

Explanation

Acamprosate is believed to modulate glutamatergic NMDA receptor activity and may reduce withdrawal-related hyperexcitability. It is used to support abstinence maintenance rather than to treat acute withdrawal.

Question 13Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Buprenorphine's ceiling effect on respiratory depression is best explained by which property?

  1. Selective agonist activity at kappa-opioid receptors
  2. Full agonist activity at mu-opioid receptors
  3. Pure antagonist activity at mu-opioid receptors
  4. Partial mu agonism with high affinity and low intrinsic efficacy Correct answer.

Explanation

Buprenorphine binds mu-opioid receptors with high affinity but has low intrinsic efficacy, producing a plateau in opioid effects as dose increases. This partial agonism limits respiratory depression compared with full agonists.

Question 14Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Varenicline aids smoking cessation by acting as which type of agent?

  1. Partial agonist at alpha4beta2 nicotinic receptors Correct answer.
  2. Full agonist at alpha4beta2 nicotinic receptors
  3. Competitive antagonist at NMDA receptors
  4. Irreversible inhibitor of monoamine oxidase B

Explanation

Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors, which reduces nicotine withdrawal and blunts the rewarding effect of smoked nicotine. It is not a full nicotinic agonist or an NMDA antagonist.

Question 15Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Disulfiram produces aversive flushing and nausea after alcohol by which mechanism?

  1. Inhibiting aldehyde dehydrogenase and raising acetaldehyde Correct answer.
  2. Blocking alcohol dehydrogenase
  3. Antagonizing opioid receptors
  4. Enhancing GABA-A receptor activity

Explanation

Disulfiram inhibits aldehyde dehydrogenase, causing acetaldehyde to accumulate when alcohol is consumed. The resulting flushing, nausea, and autonomic symptoms discourage drinking.

Question 16Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Delta-9-tetrahydrocannabinol's rewarding effects are primarily initiated by which action?

  1. Direct activation of dopamine D2 receptors
  2. CB1 agonism that modulates presynaptic neurotransmitter release Correct answer.
  3. Blockade of dopamine transporters
  4. Positive allosteric modulation of GABA-A receptors

Explanation

THC is a partial agonist at CB1 receptors, which are presynaptic Gi/o-coupled receptors that modulate neurotransmitter release. This can disinhibit ventral tegmental dopamine neurons and contribute to reward.

Question 17Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Impaired prefrontal cortical control in addiction is most closely associated with which deficit?

  1. Selective loss of spinal motor neurons
  2. Increased hippocampal neurogenesis
  3. Enhanced cerebellar motor coordination
  4. Deficits in inhibitory control and delayed discounting Correct answer.

Explanation

Prefrontal circuits support response inhibition, planning, and valuation of delayed outcomes. Their dysfunction in addiction is linked to impulsivity and steep delay discounting.

Question 18Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Stress-induced relapse to drug seeking is strongly mediated by which system?

  1. Corticotropin-releasing factor and the extended amygdala Correct answer.
  2. Nicotinic receptors at the neuromuscular junction
  3. Mu-opioid receptors in the spinal cord
  4. Dopamine D2 autoreceptors in the dorsal striatum

Explanation

Stress activates corticotropin-releasing factor systems, especially in the extended amygdala, which contribute to negative affect and relapse vulnerability. This stress circuitry is distinct from spinal or neuromuscular mechanisms.

Question 19Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Compared with cocaine, amphetamine has which additional pharmacologic action?

  1. Directly agonizing dopamine D1 receptors
  2. Inhibiting monoamine oxidase type A
  3. Reversing vesicular monoamine transport and promoting dopamine release Correct answer.
  4. Blocking dopamine reuptake at the transporter

Explanation

Both cocaine and amphetamine inhibit the dopamine transporter, but amphetamine also enters nerve terminals, reverses vesicular monoamine transport, and promotes non-exocytotic dopamine release. This additional action distinguishes amphetamine from cocaine.

Question 20Neurobiology, Etiology, and Pharmacology of Addictive Disorders

After chronic heavy alcohol use, which neuroadaptive pattern contributes to withdrawal hyperexcitability?

  1. Selective dopamine D2 receptor supersensitivity
  2. Upregulation of GABA-A receptors and downregulation of NMDA receptors
  3. Increased GABA release with unchanged glutamate function
  4. Downregulation of GABA-A receptors and upregulation of NMDA receptors Correct answer.

Explanation

Chronic alcohol exposure downregulates GABA-A receptor function and upregulates NMDA receptor activity as adaptation to sustained inhibition. When alcohol is removed, this imbalance produces hyperexcitability and withdrawal symptoms.

Question 21Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Opioid withdrawal produces autonomic hyperactivity largely because chronic mu-opioid agonism does which action?

  1. Suppresses locus coeruleus cAMP signaling, which rebounds during withdrawal Correct answer.
  2. Directly destroys locus coeruleus neurons
  3. Blocks nicotinic receptors at autonomic ganglia
  4. Increases GABA-A receptor density in the cortex

Explanation

Chronic mu-opioid agonism inhibits locus coeruleus neurons and reduces cAMP signaling. During withdrawal, cAMP activity rebounds, increasing noradrenergic outflow and producing autonomic hyperactivity.

Question 22Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Which genetic variant is associated with alcohol flushing and a lower risk of alcohol use disorder in East Asian populations?

  1. ADH1B*2, which slows alcohol metabolism
  2. DRD2 Taq1A, which increases dopamine synthesis
  3. ALDH2*2, which reduces aldehyde dehydrogenase activity Correct answer.
  4. OPRM1 A118G, which abolishes mu-opioid receptor function

Explanation

ALDH2*2 encodes a less active aldehyde dehydrogenase, leading to acetaldehyde accumulation, flushing, and unpleasant reactions to alcohol. This genotype is associated with reduced risk of alcohol use disorder.

Question 23Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Reduced dopamine D2 receptor availability in individuals with substance use disorders is often interpreted as which finding?

  1. Evidence of increased responsiveness to natural rewards
  2. A correlate of blunted reward sensitivity and addiction risk Correct answer.
  3. Proof that dopamine is unrelated to reinforcement
  4. A protective factor against compulsive drug use

Explanation

Lower striatal D2 receptor availability has been associated with reduced responsiveness to natural rewards and increased vulnerability to compulsive drug use. It is a correlate, not proof of causation.

Question 24Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Incubation of drug craving refers to which finding?

  1. Cue-induced drug seeking appears only during acute withdrawal
  2. Cue-induced drug seeking is independent of glutamate receptor plasticity
  3. Cue-induced drug seeking intensifies over the first weeks to months of abstinence Correct answer.
  4. Cue-induced drug seeking declines steadily as abstinence lengthens

Explanation

In animal models, cue-induced drug seeking can increase, or incubate, over days to weeks of forced abstinence rather than decline immediately. This intensification has been linked to synaptic plasticity in reward circuits.

Question 25Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Naloxone reverses opioid overdose by which mechanism?

  1. Inhibiting opioid metabolism
  2. Competitively antagonizing mu-opioid receptors Correct answer.
  3. Activating mu-opioid receptors
  4. Blocking NMDA receptors

Explanation

Naloxone is a short-acting competitive antagonist at mu-opioid receptors, displacing opioids and rapidly reversing respiratory depression. It does not activate opioid receptors or block NMDA receptors.

Question 26Neurobiology, Etiology, and Pharmacology of Addictive Disorders

The reward-related dopamine projection most centrally implicated in drug reinforcement originates in which brain region and terminates where?

  1. Locus coeruleus to prefrontal cortex
  2. Raphe nuclei to basolateral amygdala
  3. Ventral tegmental area to nucleus accumbens Correct answer.
  4. Substantia nigra pars compacta to dorsal striatum

Explanation

The mesolimbic pathway carries dopaminergic projections from the ventral tegmental area to the nucleus accumbens and is a central substrate for drug reward. The nigrostriatal pathway instead supports movement, while the locus coeruleus and raphe nuclei are primarily noradrenergic and serotonergic.

Question 27Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Cocaine's reinforcing effect is most directly produced by blocking which transporter in the synapse?

  1. The dopamine transporter (DAT) Correct answer.
  2. The vesicular monoamine transporter (VMAT2)
  3. The serotonin transporter (SERT)
  4. The norepinephrine transporter (NET)

Explanation

Cocaine binds the dopamine transporter and blocks dopamine reuptake, raising extracellular dopamine in reward circuits. Although cocaine also affects serotonin and norepinephrine transporters, its reinforcing action is most closely tied to dopamine transporter blockade.

Question 28Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Acute alcohol intoxication produces its principal sedative effects through which pair of actions?

  1. Dopamine D2 agonism and serotonin reuptake blockade
  2. Alpha-2 adrenergic agonism and histamine H1 blockade
  3. Mu-opioid agonism and cannabinoid CB1 activation
  4. GABA-A potentiation and NMDA receptor antagonism Correct answer.

Explanation

Alcohol acutely potentiates GABA-A receptor currents and inhibits NMDA-type glutamate receptors, producing sedation and impaired cognition. Chronic exposure leads to opposite adaptations that contribute to withdrawal.

Question 29Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Which opioid receptor subtype primarily mediates the rewarding and analgesic effects of morphine?

  1. Nociceptin/orphanin FQ receptors
  2. Delta opioid receptors
  3. Mu opioid receptors Correct answer.
  4. Kappa opioid receptors

Explanation

Mu-opioid receptors are the main targets of morphine and mediate analgesia, euphoria, and respiratory depression. Kappa and delta receptors contribute to other opioid effects but are not the primary reward receptor for morphine.

Question 30Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Caffeine's stimulant effect is primarily explained by antagonism at which receptor?

  1. Nicotinic acetylcholine receptors
  2. Dopamine D2 receptors
  3. Adenosine A1/A2A receptors Correct answer.
  4. GABA-A receptor channels

Explanation

Caffeine blocks adenosine A1 and A2A receptors, reducing inhibitory adenosine tone and increasing alertness. It does not act primarily through dopamine, GABA, or nicotinic receptors.

Question 31Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Methadone is used for opioid use disorder mainly because it acts as which type of medication?

  1. An alpha-2 adrenergic agonist
  2. A partial mu-opioid agonist with low intrinsic activity
  3. A long-acting full mu-opioid agonist Correct answer.
  4. A competitive mu-opioid antagonist

Explanation

Methadone is a full mu-opioid agonist with a long half-life that suppresses withdrawal and craving without the rapid peaks of short-acting opioids. Buprenorphine is the partial agonist, and naltrexone is an antagonist.

Question 32Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Naltrexone's action at mu-opioid receptors is best characterized as which of the following?

  1. Irreversible inhibition of opioid synthesis
  2. Competitive antagonism Correct answer.
  3. Allosteric potentiation of endogenous opioids
  4. Partial agonism with a ceiling effect

Explanation

Naltrexone competitively blocks mu-opioid receptors and prevents opioid agonists from producing reinforcement. Because it can displace agonists in dependent patients, it may precipitate withdrawal.

Question 33Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Wernicke encephalopathy in severe alcohol use disorder is most directly caused by deficiency of which nutrient?

  1. Folate
  2. Niacin
  3. Vitamin B12
  4. Thiamine Correct answer.

Explanation

Thiamine deficiency causes Wernicke encephalopathy, which can progress to Korsakoff syndrome if untreated. Alcohol use disorder increases risk through poor nutrition and impaired absorption.

Question 34Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Which genetic variant is associated with faster ethanol oxidation to acetaldehyde and a lower risk of alcohol use disorder?

  1. ADH1B*2 (rs1229984) Correct answer.
  2. DRD2 Taq1A (rs1800497)
  3. ALDH2*2 (rs671)
  4. OPRM1 A118G (rs1799971)

Explanation

ADH1B*2 encodes a faster alcohol dehydrogenase that increases acetaldehyde formation, producing flushing and aversion and lowering alcohol use disorder risk. ALDH2*2 also affects risk but slows acetaldehyde clearance rather than accelerating ethanol oxidation.

Question 35Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Twin and adoption studies best support which estimate of the heritability of alcohol use disorder?

  1. Approximately 50% Correct answer.
  2. Approximately 5%
  3. Essentially 0%
  4. Approximately 90%

Explanation

Twin and adoption studies indicate that alcohol use disorder is substantially heritable, with estimates around 50%. Heritability is population-level and does not mean that half of an individual's risk is fixed by genes.

Question 36Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Chronic nicotine exposure produces which characteristic change in brain nicotinic acetylcholine receptors?

  1. Downregulation of all nicotinic receptor subtypes
  2. Immediate reversal of receptor desensitization
  3. Upregulation of nicotinic binding sites Correct answer.
  4. Complete loss of alpha4beta2 receptor expression

Explanation

Chronic nicotine exposure typically upregulates high-affinity nicotinic acetylcholine receptor binding sites, especially alpha4beta2-containing receptors. This upregulation coexists with receptor desensitization and contributes to withdrawal.

Question 37Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Dynorphin acting at kappa opioid receptors is most closely linked to which addiction-related process?

  1. Stimulation of respiratory drive
  2. Euphoria and increased social reward
  3. Stress-induced negative affect and relapse Correct answer.
  4. Analgesia without any accompanying affective change

Explanation

Dynorphin acting at kappa opioid receptors produces dysphoria and stress-like effects and is implicated in stress-induced relapse. This system is distinct from mu-opioid reward and from CRF-driven stress responses.

Question 38Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Cannabinoid CB1 receptors in the brain are predominantly located where and act through which signaling pattern?

  1. Postsynaptically, where they open chloride channels
  2. Inside the nucleus, where they alter gene transcription directly
  3. Presynaptically, where endocannabinoids suppress neurotransmitter release Correct answer.
  4. On glial cells, where they increase glutamate reuptake

Explanation

CB1 receptors are presynaptic Gi/o-coupled receptors that respond to retrograde endocannabinoids and suppress neurotransmitter release. This positioning lets endocannabinoids modulate both excitatory and inhibitory synapses.

Question 39Neurobiology, Etiology, and Pharmacology of Addictive Disorders

A patient with ultrarapid CYP2D6 metabolism is prescribed codeine. Which risk is most increased?

  1. Excessive conversion of codeine to morphine and opioid toxicity Correct answer.
  2. Immediate allergic reaction to codeine
  3. Increased renal excretion of codeine without CNS effects
  4. Reduced conversion of codeine to morphine and consequently poor analgesia

Explanation

Codeine is a prodrug converted to morphine largely by CYP2D6. Ultrarapid metabolizers convert more codeine to morphine and can develop opioid toxicity at standard doses.

Question 40Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Lofexidine alleviates opioid withdrawal signs by acting as which type of medication?

  1. Direct mu-opioid receptor agonist
  2. Alpha-2 adrenergic agonist Correct answer.
  3. Competitive mu-opioid receptor antagonist
  4. GABA-B receptor agonist

Explanation

Lofexidine is an alpha-2 adrenergic agonist that reduces noradrenergic hyperactivity during opioid withdrawal. It relieves autonomic symptoms but does not reverse opioid receptor blockade.

Question 41Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Buprenorphine can precipitate withdrawal in a person physically dependent on full mu-opioid agonists because it has which property?

  1. Very low affinity for the mu-opioid receptor
  2. Pure antagonism with no measurable intrinsic activity
  3. High mu-opioid affinity with partial agonism Correct answer.
  4. Selective kappa-opioid agonism

Explanation

Buprenorphine binds mu-opioid receptors with high affinity and only partial intrinsic activity. In a patient maintained on a full agonist, it can displace the full agonist and precipitate withdrawal.

Question 42Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Repeated episodes of alcohol withdrawal are thought to increase seizure risk through which phenomenon?

  1. Tolerance to benzodiazepines
  2. Sensitization of adenosine receptors
  3. Kindling Correct answer.
  4. Reverse tolerance to alcohol

Explanation

Kindling refers to the progressive increase in withdrawal severity, including seizure risk, with repeated withdrawal episodes. It reflects long-lasting neuroadaptive changes in excitability.

Question 43Neurobiology, Etiology, and Pharmacology of Addictive Disorders

In incentive-sensitization theory, mesolimbic dopamine transmission is most closely tied to which component of addiction?

  1. Withdrawal-related autonomic signs
  2. The hedonic pleasure of drug consumption
  3. Pathological wanting and incentive salience Correct answer.
  4. Drug clearance by the liver

Explanation

Incentive-sensitization theory distinguishes pathological 'wanting' from hedonic 'liking' and assigns a central role to mesolimbic dopamine in incentive salience. The pleasure of consumption is not identical to dopamine-mediated wanting.

Question 44Neurobiology, Etiology, and Pharmacology of Addictive Disorders

During early abstinence from chronic cocaine, which neurochemical state contributes to anhedonia and depressed mood?

  1. Reduced dopaminergic transmission Correct answer.
  2. Excess norepinephrine reuptake
  3. Increased dopamine release in the nucleus accumbens
  4. Upregulation of dopamine D2 receptors

Explanation

Chronic cocaine use can deplete dopamine and downregulate reward circuitry, producing anhedonia and depressed mood during early abstinence. These symptoms reflect reduced dopaminergic transmission rather than excess dopamine.

Question 45Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Baclofen is sometimes used off-label for alcohol use disorder because it acts as which type of agent?

  1. Mu-opioid receptor antagonist
  2. GABA-B receptor agonist Correct answer.
  3. GABA-A receptor positive allosteric modulator
  4. Glutamate NMDA receptor agonist

Explanation

Baclofen is a GABA-B receptor agonist that can reduce alcohol craving and use in some patients. It is not a GABA-A modulator, opioid antagonist, or NMDA agonist.

Question 46Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Cue-induced cocaine seeking after prolonged abstinence is most strongly associated with which synaptic change in the nucleus accumbens?

  1. Loss of essentially all glutamatergic synapses
  2. Selective deletion of dopamine D1 receptors
  3. Increased surface AMPA receptor expression Correct answer.
  4. Upregulation of GABA-A chloride conductance

Explanation

Prolonged abstinence after cocaine self-administration is associated with increased surface AMPA receptor expression and glutamatergic plasticity in the nucleus accumbens. These changes enhance cue-induced seeking and are linked to incubation of craving.

Question 47Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Long-term opioid therapy can paradoxically increase pain sensitivity through which proposed mechanism?

  1. NMDA receptor-mediated central sensitization Correct answer.
  2. Downregulation of spinal NMDA receptors
  3. Enhanced GABAergic inhibition in the dorsal horn
  4. Increased endogenous opioid release

Explanation

Opioid-induced hyperalgesia is proposed to involve NMDA receptor-mediated central sensitization and descending facilitation. This can make pain worse despite continued opioid exposure.

Question 48Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Adolescents show heightened vulnerability to substance use disorders partly because of which developmental pattern?

  1. Absence of dopamine receptors in the adolescent brain
  2. Complete myelination of prefrontal cortex before puberty
  3. Later maturation of prefrontal control than limbic reward circuits Correct answer.
  4. Earlier maturation of prefrontal control compared with limbic reward circuits

Explanation

Adolescent brain development features earlier maturation of limbic reward circuits than of prefrontal control circuits. This imbalance can favor impulsive and sensation-seeking behavior during a period of high plasticity.

Question 49Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Chronic heavy alcohol use increases the hepatotoxic risk of acetaminophen mainly by which mechanism?

  1. Induction of CYP2E1 and increased toxic metabolite formation Correct answer.
  2. Inhibition of acetaminophen glucuronidation
  3. Depletion of glutathione without any change in drug metabolism
  4. Reduction of CYP2E1 activity

Explanation

Chronic alcohol induces CYP2E1, which converts acetaminophen to the toxic metabolite NAPQI. Combined with glutathione depletion, this increases hepatotoxicity risk.

Question 50Neurobiology, Etiology, and Pharmacology of Addictive Disorders

Tolerance to benzodiazepines after long-term use is best explained by which receptor-level adaptation?

  1. Conversion of GABA-A receptors into NMDA receptors
  2. Complete loss of GABA-A receptors from the synapse
  3. Increased benzodiazepine binding without functional change
  4. Changes in GABA-A subunit composition and decreased potentiation Correct answer.

Explanation

Long-term benzodiazepine use can produce tolerance through changes in GABA-A subunit composition and reduced positive modulation. Receptors are not generally lost entirely or converted into other receptor types.