L22: Neurobiology of Addiction Flashcards
What is addiction (3 main characteristics)?
What characterizes the severity of the disease?
A chronic relapsing disorder characterized by:
1) Compulsion to seek and take drug
2) Loss of control in limiting intake
3) Emergence of a negative emotional state when access to the drug is prevented
Diagnosed by 11 diagnostic criteria, and severity depends on how many of these criteria the person meets (2/11=mild, 4/11=moderate, 6+/11= severe)
What type of disease is addiction?
Biopsychosocial disease
Biological factors can increase your likelihood of developing an addiction and can promote continued drug use
Risky drug use is associated with low SES, homelessness, social isolation, early life trauma.
Interventions need to target BOTH psychosocial and biological factors
What is the first stage in the cycle of addiction?
- Initial drug use: genetics (impulsivity), differences in monoamine NT metabolism (respond to different drug doses differently)
- mood (depression and anxiety)
What is the second stage in the addiction cycle?
- Continued drug use: associated with the positive effects of drug (euphoria, reduced anxiety, analgesia), driven by positive reinforcement
Incentive salience increases overtime (motivation for rewards that is learned by previously learned associations about reward)
Incentive sensitization
What is the third stage in the cycle of addiction?
- Drug withdrawal: opposite effects of acute drug use (dysphoria, increased pain, anxiety), unpleasant symptoms can drive craving and relapse, withdrawal symptoms get worse with chronic drug use
Some drugs have lethal withdrawal symptoms, others have long term withdrawal that is unpleasant and promotes continued drug use to avoid the bad symptoms
The desire to avoid withdrawal can promote continued drug use (negative reinforcement)
What is the final stage of the cycle of addiction?
- Compulsive drug use: shift from impulsive (risk taking and experimenting) to compulsive drug use (know consequences and do it anyway)
Shift from positive reinforcement to negative reinforcement to avoid feeling bad
What is the system that is responsible for promoting motivated behaviour?
Mesolimbic dopamine system
Dopamine containing neurons in the VTA project to the ventral striatum (mesolimbic) and prefrontal cortex (mesocortical)
Dopamine release occurs following a salient stimuli (drug) and promotes motivated behaviour (LEARNING)
How does the mesolimbic dopamine system work?
Midbrain dopamine is responsible for incentive salience, invigorate goal directed activity or general activation.
Rate of dopamine increase (above baseline level) is important to determine function.
Phasic burst associated with salience and reward, and deficits in dopamine signaling are associated with depression and anhedonia (no pleasure)
What does a phasic burst of dopamine indicate?
It indicates the salience of rewarding cues, not necessarily signal the reward itself
A phasic burst will happen when you anticipate the reward, even when it does not actually come (DA neurons fire despite no reward)
What is something that all drugs of abuse do?
ALL evoke dopamine release (through different mechanisms)
What are two examples of different mechanisms in drugs of abuse that cause DA release?
Opioids bind to mu opioid receptor on inhibitory GABAergic interneurons in the VTA, thus inhibiting the inhibition (because mu opioid receptors are inhibitory) and more dopamine is released
Psychostimulants (cocaine) block the dopamine transporter inhibiting reuptake of the NT into the presynaptic terminal and increased synaptic levels of DA
TRUE OR FALSE: Midbrain dopamine is required for psychostimulant reward but NOT opioid reward
TRUE, there must be DA release in the synapse already in order for the psychostimulants to work, BUT opioids actually cause the release
What is involved in the neurocircuitry adaptation in the transition to addiction?
Compulsive drug use is associated with incentive sensitization (amplification of drug wanting triggered by drug cues)
Driven by sensitization of mesolimbic dopamine system (amount of drug/cues evoke larger DA dependent behavioural responses)
Drives drug craving
Also recalibrates dopamine thresholds for natural rewards, leading to narrowing of focus to obtain drug-related rewards
Drug withdrawal is associated with deficits in dopamine tone, and lower tonic DA associated with anhedonia and depression and contributes to negative affective state od drug abstinence
How is the prefrontal cortex involved in addiction?
Glutamate afferents project from cortex to the striatum and increase DA levels.
Drug cues activate orbital frontal cortex in addicted (and not non-addicted) people
Glutamate release increase glutamate receptor expression (AMPA), and LTP at DA synapses in striatum (increased DA signaling)
How is the amygdala involved with addiction?
Central amygdala is a nucleus in the limbic brain associated with fear and anxiety
Neuropeptide release (CRF) in central amygdala causes anxiety
Drug withdrawal assoc with increased CRF in amygdala, and increased CRF assoc with aversive states of withdrawal
Contributes to increased drug-seeking behaviour in dependent animals
Blocking CRF signaling is effective at reversing symptoms of drug withdrawal and drug seeking behaviour
