Addiction and relapse Flashcards
Teacher: Marchant
What does drugs do?
It modifies brain activity through specific pharmacological compoundsv
What is an addiction?
A chronic, relapsing brain disease
What is the clinical term for addiction?
Substance use disorder (SUD)
In which to categories can you class a diagnosis?
Pharmacological related
Psychology related
How is severity of SUD classed?
In gradations instead of binary
What are the individual risk factors for addiction?
- Each brain is different = different perception
- GWAS show that genes are part of it: alcohol/nicotine/opioid use disorder genes
- Co-morbidity; addiction comes alone –> psychological disorders, personality traits, learning disabilities
What are environmental factors for addiction?
- Family environment
- Peer influence
- Socioeconomic factors
- Access and availability (to drugs)
- Stress exposure and coping mechanism
- Cultural attitudes (social acceptance,norms,traditions)
What are drug-specific factors for addiction?
- ‘Risk’ of addiction of the drugs –> not the same for every drug
- Method of administration
- Frequency & intensity of use
What are gene-evironmental interactions that could create addiction?
Multiple risk factors combining –> having family history(genes) + high level stress environment + traumatic life experiences
What are protective factors for addiction?
- Strong social support
- Good coping skills (manage triggers)
- Access to healthcare (education and awareness)
Which neuromodulator pathway is involved in drug use?
The dopamine pathways for reward
What can be seen in cocaine and heroin reward when there is a lesion in the dopamine system? And what does this mean?
It decreases cocaine reward but not heroin reward.
- Also in absence in dopamine there is still reward
What is the role of dopamine in reward?
- It has a role in learning, motivation and pursuit but really for reward
What is beside dopamine also involved in reward neurobiology? And where in the brain do they come from?
- Endogenous opioids from the VTA, Nucleus Accumbens, Amygdala
What short-term/immediate effects can be seen after taking in drugs?
- Sudden flood of neurotransmitters
- Increased heart rate & blood pressure
- Impaired judgement & coordination
- Altered time perception
What changes can be seen in the brain in drug use?
- Reduced D2-receptor availability (D2 = dopamine inhibiting factor)
- Reduction in cortical thickness
- Long-term morphine-induced changes in dendritic morphology of neurons in the reward system
- Changes in spine density in prefrontal areas (number of spines & branching patterns)
Neurobiological theories on addiction:
What is the opponent-process theory?
Transition from positve reinforcement (drug reward) to negative reinforcement (drug alleviating negative emotions)
Neurobiological theories on addiction:
What is the incentive-sensitization theory?
Excessive ‘incensive salience’ to drug and drug-associated stimuli
Neurobiological theories on addiction:
What is the aberrant learning theory?
Repeated drug use reinforces drug-related stimuli and actions to pathological levels (excessive dopamine = excessive learning)
Neurobiological theories on addiction:
What is the habit theory?
Progressive development and dominance of drug habits over goal-directed control
What are the 3 elements of the addiction cycle?
- Binge/intoxication
- Withdrawal/negative affect
- Preoccupation/anticipation
–> cycle become stronger over time
What is involved in Binge/intoxication?
Rewarding effects of most drugs: basal ganglia,VTA, naturally occurring opioids
–> habit formation via dordal striatum
- Explaines what triggers cravings and use
- Positive reinforcement
consuming an intoxicating substance and experiences its rewarding/pleasurable effects
What is involved in withdrawal/negative affect?
- Decrease in function of the brain reward system –> increase in the anti-reward system
- Activation of stress neurotransmitters in the extended amygdala
- Negative reinforcement
experiencing a negative emoitonal state in the absence of the substance
What is involved in preoccupation/anticipation?
- Disruption of executive function caused by a compromised prefrontal cortex (decision-making, impulsivity, craving)
- Glutamate is increased, driving ‘substance use’ habits, and disrupts how dopamine influences the frontal cortex
Seeking substances again after a period of abstinence
What is another term for loss of control in addiction?
The Breaking Brake System
What does preclinical research enable us to do?
- Study brain mechanisms in detail
- Test new treatment strategies
- Identify risk factors
- Understand addiction development
- Develop prevention strategies
What is operant conditioning?
Learning process in which voluntary behavior is modified by association with the addition of reward or aversive stimuli
What is the definition of relapse?
Resumption of drug use after a period of abstinence –> craving
What are common triggers for relapse?
- Cues (induce cravings)
- Drug priming (lapse causes relapse)
- Stress
What is a methodological approach to research what brain regions are active during specific behaviors?
- Behavior-related cFos: looks at fos expression (lot of Glu = lot of Fos expression)
- Calcium imaging
What are neuronal ensembles?
Small subset of selectivly activated neurons that encode the learned associations
Brain activity in which brain structure is correlated with relapse?
Insula
What is GECI?
Genetically Encoded Calcium Indicator
Why is GECI used?
- It targets specific populations
- Can be used within session changes in bulk neuronal activity
Why is calcium used to detect neuronal activities?
Ca2+ is most attractive ion target:
- Ca2+ influx is the first step in neuronal activation
- Intracell. concentrations rises transiently during electrical activity
Voltage:
- Detailed temporal signal
- Electrophysiology records voltage –> true measure for APs
In the fiber photometry study with rats in the anterior insula, what was found during self-administration?
Anterior Insula activity highest in response to nicotine infusion
In the fiber photometry study with rats in the anterior insula, what was found during punishment?
Anterior Insula activity related to highest after response-contingent shock punishment
In the fiber photometry study with rats in the anterior insula, what was found during relapse?
Only significant difference between the outcomes was prior to an active nose-poke compared to inactive nose-poke
What is DREADD?
Proteins manipulated to react specifically with small molecules which act as chemical actuators, but which were not previously recognized by these proteins
What are the required attributes of a DREADD?
- No endogenous ligand
- Free of basal activity
- Exclusively and potently activated by an otherwise pharmacologically inert compound
What could targeted interventions of anterior insula possibly do?
Decrease cue or environment triggered relapse in humans
For what is alC activity necessary?
For context-induced relapse after both punishment and extiniction
