Week Four - Addiction Neuroscience Flashcards
What is the definition of addiction?
There is no single, universally accepted definition of addiction.
Why are there criticisms of addiction being a ‘brain disorder’?
Because it disregards human decision making and choice
What does the DSM-5 regard addiction as?
substance-related and addictive disorder
Substance-related disorders are classified into what 2 groups?
Substance use disorders
Substance-induced disorders
What do Substance use disorders involve?
Involve a cluster of cognitive, behavioural, and physiological symptoms as well as continued use of the substance despite significant substance-related problems.
Substance abuse disorder disorder contains what 9 classes of drugs?
alcohol, cannabis, hallucinogens, PCP, opioids, inhalants, sedatives, stimulants, or tobacco.
What do Substance-induced disorders include?
substance intoxication, substance withdrawal, and other substance/medication-induced mental disorders.
severity of substance-induced disorder depends on what?
How many criteria are met
2-3: mild
4-5: mod
6+: severe
What is the cause of of substance use disorders and addictive behaviour?
No single cause, but a product of enviro and physiological factors
Why are animal models ‘limited’ or criticised?
Because humans manipulate the addiction environments
How does the drug cycle begin?
Positive reinforcement: pleasurable effects reinforce drug use
Negative reinforcement may also however explain initial drug use in those who use drugs to escape distress/stress
Why does compulsive drug-taking occur?
Because the rewarding effects of drug use are reduced and there is a need to achieve a state of homeostasis (neg reinforcement)
Addiction shares features of what 2 disorders?
Impulsive and compulsive
When does negative reinforcement occur during drug taking?
When drug taking is driven by the need to reduce anxiety/stress
A shift from pos to neg reinforcement is evident when?
An individual transits from an impulsive disorder to compulsive disorder
What is a common feature of all addictive drugs?
They activate reward pathways in the brain by triggering the release of dopamine
What do reward pathways refer to?
The connections between striatal, midbrain, limbic and prefrontal regions of the brain known as the mesocorticolimbic pathways
Where do drugs such as amphetamine, cocaine, nicotine and morphine as well as food and sex elevate dopamine transmission?
in the nucleus accumbens (heavily innervated by dopamine fibres)
How do drugs create an illusion in the nucleus accumbens?
By creating an illusion and tricking the brain by imitating the release of chemicals associated with motivation
Lesioning the dopamine system at the level of the nucleus accumbus does what?
prevents the acquisition of cocaine and nicotine self-administration in rodents suggesting that dopamine mediates the enforcing effects of each.
What further substantiates dopamines involvement in addiction - parkinson’s?
D agonists often block the rewarding effects of drugs.
Humans with PD report having blunted effects of stimulants
What is drug addiction often characterised by?
Anhedonia (failure to experience rewarding stimuli)
In addition to the dopamine system, the serotonergic system plays a critical role in what?
Mediating the experience of pleasure as evidenced by depression research
What other 2 NT also play a role in addiction?
GABA
- opiates increase dopamine in part by removing the inhibitory influence of GABA on dopamine releasing cells
- GABA agonists have been found to reduce drinking, decrease craving ad improve sleep in those with alc use disorder
GLUTAMATE
- low glutamate levels in peeps with alc use disorder
Addiction leads to changes in (5)
synaptic plasticity
dendritic size and spines
white and gray matter
up/down-regulation of receptors
intracellular signalling pathways
What is synaptic plasticity?
The ability of synaptic connections to strengthen or weaken as a result of increased or decreased activity
What two receptions have received attention in SP?
NMDA and AMPA glutamate receptors
NMDA and AMPA glutamate receptors are typically involed in what?
long-term potentiation
What is LTP?
LTP refers to increased efficiency of neurotransmission and plays a critical role in learning and memory.
Changes in SP are observed in what?
Drug sensitisation (an enhanced response to the drug that is observed following repeated exposure; also known as reversed tolerance)
What did amphetamine treatment do to mices dendritic arbours/spines?
It increased the size of the in the nucleus accumbens and increased the number of spines these neurons had on their dendrites
What was elevated in animals treated with amphetamine?
What did this demonstrate?
The number of glutamatergic synapses in the nucleus accumbens.
This region of the brain becomes hyper-excitable following chronic amphetamine exposure
Robinson et al. (2001) found structural changes in dendrites located in the prefrontal cortex of rats that self-administered cocaine. What were these changes?
The dendrites of cells of the rats that self-administered cocaine were misshapen, with large, bulbous structures at their tips. - linked to impaired decision making and judgement
Current technology does not enable what?
Dendritic density and size measurements in humans
Studies have consistently reported what in regard to grey matter and substance use disorders? (2)
Gray matter volume reductions in the prefrontal regions and additional mesocorticolimbic structures.
Drug craving was negatively associated with gray-matter volume
White matter and substance use disorder findings? (2)
Reduced white matter has been found in participants with substance use disorders.
Significant loss of cerebral white matter found in postmortem and living individuals with alcohol use disorder
Rivkin et al. (2008) reported that children exposed to cocaine, tobacco, marijuana, or alcohol in utero had what?
Smaller head circumference and white and gray matter
Opioid use disorder is associated with changes to what?
White matter and gray matter changes in brain regions implicated in addiction including those involved in the regulation of impulse control, as well as in reward and motivational functions
Several studies have found what in regard to receptor regulation? Volkow and colleagues (1996)
Decreased density of postsynaptic dopamine receptors (D2) in participants with substance use disorder
Chang, Alicata, and Volkow (2007) found reduced dopamine transporter density and reduced dopamine D2 receptors in what area of the brain?
The striatum
Continued use of substances is associated with what?
Continued use is associated with complex intracellular changes.
Intracellular changes are believed to be responsible for?
Tolerance, addiction and withdrawal
What is one important intracellular change associated with drug addiction?
up-regulation of the (cAMP) pathway.
What is CREB?
A protein that plays a key role in learning and memory.
When is CREB induced?
Following chronic exposure to drugs such as stimulants and opiates.
An increase in phosphorylated CREB correlates with what?
Diminished sensitivity to drug-induced reward.
How is CREB linked with tolerance/dysphoria/withdrawal?
CREB provides a compensatory mechanism that responds to drugs
Over-expression of ΔFosB does what?
increases sensitivity to the rewarding and reinforcing effects of stimulants
What does the raclopride method allow?
Estimation of dopamine levels through competitive binding to D2 receptors
After Methylphenidate-induced increases in the striatal dopamine in controls and in detoxified cocaine abusers what happens?
Cocaine abusers and alcoholics show decreased dopamine increases and report reduced reward effects of MP
What can drugs cause?
Hypodopaminergia
What is Hypodopaminergia
depletion of monoamine stores in the brain, inducing depressive-like symptoms
What is Hypodopaminergia linked to? (2)
Anhedonia: inability or difficulty to experience pleasure
Hypofrontality: decrease activation of PFC - compromising planning/decision making
What is a challenge for neurobiology?
To understand why some individuals become addicted while others do not
What is a key to the current challenge for neurobiology? How?
Differences in reward circuits
Subjects with high d2 receptors = effects of MP not pleasant
Subjects with low d2 receptors = MP effects are pleasant
Overexpression of D2 receptors in the NAcb in rats did what?
Reduces alcohol preference and self-administration
Impulsive rats were found to have what?
Lower D2 receptors
In humans, low densities of D2 receptors were associated with?
Decreased metabolism in the orbitofrontal cortex - associated with OCD and impulsivity
