Neurobiology of Addiction Flashcards

Which neurotransmitter is primarily associated with the reward pathway in addiction?

Answer: Dopamine

Dopamine is the primary neurotransmitter in the mesolimbic reward pathway and is central to the reinforcing effects of all major addictive substances.

The mesolimbic dopamine pathway originates in which brain region?

Answer: Ventral tegmental area

The mesolimbic pathway originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens, forming the brain's primary reward circuit.

What neuroadaptation to repeated drug exposure is the primary basis of tolerance?

Answer: Downregulation of dopamine receptors

Repeated drug exposure leads to downregulation of dopamine receptors, so more drug is required to produce the same effect, which is the cellular basis of tolerance.

Which brain region plays the most central role in drug craving and reward processing?

Answer: Nucleus accumbens

The nucleus accumbens, part of the ventral striatum, is the primary target of dopamine from the VTA and is critically involved in reward processing, craving, and drug-seeking behavior.

The 'allostatic model' of addiction describes which phenomenon?

Answer: A chronic shift in the brain's reward set point leading to negative affect

The allostatic model describes how repeated drug use shifts the brain's hedonic set point downward, resulting in chronic negative affect and driving continued use to restore a sense of normalcy.

Which system becomes hyperactive during drug withdrawal and contributes to dysphoria and anxiety?

Answer: Brain stress systems including CRF and dynorphin

Brain stress systems, particularly corticotropin-releasing factor (CRF) and dynorphin, become hyperactive during withdrawal, producing dysphoria and negative affect that powerfully drive relapse.

In the context of addiction, neuroplasticity refers to:

Answer: Persistent drug-induced changes in neural structure and function that underlie compulsive behavior

In addiction, neuroplasticity refers to lasting drug-induced changes in synaptic structure and function, including dendritic remodeling and altered gene expression, that underlie compulsive drug-seeking.

How do opioids primarily produce their analgesic and euphoric effects?

Answer: By activating mu-opioid receptors coupled to inhibitory G proteins

Opioids bind to mu-opioid receptors (as well as delta and kappa receptors), which are Gi-coupled and reduce neuronal excitability, producing analgesia and euphoria through downstream dopamine release.

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

Answer: Potentiation of GABA-A receptors and inhibition of NMDA glutamate receptors

Alcohol enhances inhibitory GABAergic neurotransmission at GABA-A receptors and inhibits excitatory glutamatergic neurotransmission at NMDA receptors, producing CNS depression.

Why does abrupt alcohol withdrawal cause seizures?

Answer: Rebound NMDA receptor hyperactivity and reduced GABA function due to neuroadaptation

Chronic alcohol use upregulates NMDA receptors and downregulates GABA-A receptors; abrupt cessation leaves the brain in a hyperexcitable state due to these neuroadaptations, leading to seizure risk.

What is the primary mechanism by which cocaine produces its euphoric effects?

Answer: Blocking reuptake transporters for dopamine, norepinephrine, and serotonin

Cocaine blocks monoamine reuptake transporters (DAT, NET, SERT), flooding the synapse with dopamine, norepinephrine, and serotonin, with dopamine accumulation in the nucleus accumbens producing intense euphoria.

What role does the prefrontal cortex play in addiction?

Answer: It mediates impulse control and decision-making, both of which are impaired in addiction

The prefrontal cortex mediates executive functions including inhibitory control and decision-making; dysfunction of this region in addiction results in impaired control over drug-seeking despite negative consequences.

The endocannabinoid system's primary role in addiction neurobiology involves:

Answer: Modulating synaptic plasticity and reward processing via CB1 and CB2 receptors

The endocannabinoid system, through CB1 and CB2 receptors, modulates synaptic plasticity and reward processing and plays a key role in the motivational aspects of multiple substance use disorders.

Which neurobiological change is particularly severe and long-lasting in methamphetamine addiction?

Answer: Dopaminergic neurotoxicity with loss of striatal dopamine terminals

Methamphetamine causes significant dopaminergic neurotoxicity through oxidative stress and excitotoxicity, leading to loss of dopamine nerve terminals in the striatum that can persist for years.

What percentage of addiction vulnerability is estimated to be attributable to genetic factors?

Answer: 40–60%

Twin and family studies consistently estimate that genetic factors account for approximately 40–60% of the risk for developing substance use disorders, with the remainder due to environmental factors.

Epigenetic changes in addiction refer to:

Answer: Heritable changes in gene expression without alteration of the underlying DNA sequence

Epigenetic changes such as DNA methylation and histone modification alter gene expression without changing the DNA sequence and may persist or be passed to offspring, linking environment to heritable biology.

The OPRM1 A118G polymorphism is clinically relevant in addiction medicine because it:

Answer: Predicts differential response to naltrexone treatment for alcohol use disorder

The OPRM1 A118G variant affects mu-opioid receptor function and has been associated with differential response to naltrexone, with some evidence that carriers of the G allele show better treatment outcomes.

Which concept best explains why some individuals can use substances recreationally without developing addiction while others progress to compulsive use?

Answer: Gene-environment interactions affecting neurobiological vulnerability

Gene-environment interactions, where genetic predispositions interact with environmental factors such as trauma, stress, and age of first use, determine neurobiological vulnerability to addiction.

What is 'incentive salience' in addiction neurobiology?

Answer: The process by which drug-associated cues acquire powerful motivational significance driving drug-seeking

Incentive salience, driven by dopamine in the nucleus accumbens, is the process by which conditioned stimuli associated with drug use acquire intense motivational value, eliciting craving and drug-seeking when encountered.

Long-term potentiation (LTP) in addiction research is significant because it:

Answer: Represents a cellular mechanism by which drug-associated memories become deeply and persistently encoded

LTP in regions such as the amygdala and nucleus accumbens underlies the formation of powerful, persistent drug-associated memories that contribute to craving and relapse risk even after prolonged abstinence.