Week 4: Addiction neuroscience Flashcards
What is the definition of addiction?
There is no universally accepted definition
Addiction as a brain disease?
It has contributed to eliminating some of the stigmas associated with addiction
No longer considered moral failure or a lack of willpower
What is a criticism of addiction being seen as a brain disease?
It disregards human decision making and choice
What makes addiction different from classical diseases?
It is a group of behaviours, not an illness
Cannot be explained by a disease process
It is not an infectious disease
What does the DSM-5 call addiction?
It is under substance-related and addictive disorders
What are the 9 classes of drugs that may be involved in addiction?
Alcohol Cannabis Hallucinogens PCP Opioids Inhalants Sedatives Stimulants Tobacco
The severity of an addiction depends on what?
How many criteria are met
What is a mild addiction?
2-3 criteria
What is a moderate addiction?
4-5 criteria
What is a severe addiction?
6+ criteria met
What is the cause of substance use disorders?
Thought to be a product of environmental and physiological factors
Explain positive reinforcement of drug addiction
Models suggest pleasurable effects of using a drug reinforce initial drug use
Over time, the rewarding effects of the drug are….
Reduced and drug-taking becomes compulsive
Explain negative reinforcement of drug addiction
When drug-taking behaviour is used as a way of achieving homeostasis (to feel normal or alleviate pain, discomfort or withdrawal)
Addiction shares features with which kind of disorders?
Impulsive and compulsive disorders
George Koob proposes that as an individual transit from an impulsive disorder to a compulsive disorder there is a shift from positive reinforcement to negative reinforcement driving the motivation for drug taking
Dopamine in parkinsons?
Those with Parkinsons have compromised levels of dopamine in their nucleus accumbens - they report blunted effects to stimulants
Opiates increase dopamine by…
Removing the inhibitory influence of GABA on dopamine-releasing cells
Addictive drugs activate reward pathways in the brain. How?
By triggering the release of dopamine
Drugs and LTP?
Cocaine exposure has been found to increase LTP in ventral tegmental areas lasting for days to months
Opioids, cannabis and alcohol all have been found to elicit LTP in mesolimbic and mesocortical projection areas
Dopamine in the nucleus accumbens?
It is a region in the central striatum that is heavily inadverted by dopamine fibres
- Some drugs elevate dopamine transmission here
- Food and sexual activity can also activate
Rats self-administering cocaine?
Dopamine levels in the nucleus accumbens increased during self-administration of intravenous cocaine
Dopamine antagonists decreased lever pressing by blocking the rewards of the drugs
What is gabapentin and what has it been found useful for?
It is a GABA agonist
Found to reduce drinking, decrease cravings in those with alcohol use disorder
Glutamate in addiction?
Addicts have lower levels of glutamate in their forebrains
What is synaptic plasticity?
The ability of synaptic connections to strengthen or weaken as a result of increased or decreased activity
Do those with substance use disorders have any differences in their white matter? What is an example of this?
Reduced white matter has been found in participants with substance use disorders.
A large number of studies have reported a significant loss of cerebral white matter found in postmortem and living individuals with alcohol use disorder
What is LTP?
Long term potentiation
- Increased efficiency of neurotransmission with a critical role in learning and memory
What happens to neurons with repeated drug use?
They adapt overtime - perhaps responsible for tolerance, addiction, and withdrawal
What intracellular pathway in the brain is activated with the administration of addictive drugs?
Cyclic adenosine monophosphate (cAMP) pathway
Are there any structural changes in the neurons of rats that self-administer cocaine? What might these changes lead to?
Prefrontal cortex
- Dendrites misshapen, large bulbous tips
Speculations claimed that these changes are linked to impaired decision making and judgements that are typical of human cocaine abusers
What is grey matter?
Brain tissue containing cell bodies with unmyelinated axons
Do drugs affect grey matter?
Studies have consistently reported gray matter volume reductions in the prefrontal regions and additional mesocorticolimbic structures
What else might grey matter volume reductions be associated with?
Drug craving
What is white matter?
refers to tracks of myelinated axons
When exposed to substances in utero, are there any consequential differences in the brain?
Children exposed to cocaine, tobacco, marijuana, or alcohol in utero have smaller head circumference and white and gray matter relative to children not exposed to these substances
Explain the changes in postsynaptic dopamine receptors in substance use disorders
Studies have found decreased density of D2 dopamine receptors in those with substance use disorders relative to controls
This is an important feature in addiction
How do we measure dopamine release in the brain?
Binding assay combined with positron emission therapy
What receptors are linked to the cAMP pathway?
Dopamine receptors
What is raclopride used to measure and what is commonly seen with these measurements?
Used to measure dopamine levels through competitive binding to DA D2 receptors
If there is high raclopride binding - means low dopamine
If there is low raclopride binding - means high dopamine (more to compete and not as much binding)
What happens to CREB when it is targetted by cAMP?
It becomes phosphorylated (becoming pCREB)
What happens when there is an increased amount of phosphorylated CREB?
There is diminished sensitivity to drug-induced reward
How is CREB linked with tolerance?
May provide a compensatory mechanism that responds to drugs
Why can’t methylphenidate produce dopamine transmission in ex-cocaine abusers?
Suggests compromised activity of the dopamine system
As well as long-term neural adaption in that these are ex-users
What does an over-expression of delta fosB lead to?
Increases sensitivity to the rewarding and reinforcement effects of stimulants
Give an experimental example of drug escalation
When rats are exposed to a drug for self-administration over extended periods of time, they behave differently compared to rats with short access
With long access, the administration started to increase significantly from a certain point (drug escalation)
How do we measure dopamine release in the brain?
Binding assay with combined with positron emission therapy
What is the inability to experience pleasure called?
Anhedonia - very typical symptom in addiction
What else might hypodopaminergia be associated with?
Hypofrontality - decreased activation in the prefrontal cortex
What are the effects of methylphenidate similar to?
Similar to cocaine
What happens when methylphenidate is used in controls and detoxified cocaine users?
Methylphenidate doesn’t have the same ability to produce increases in dopamine transmission of previous cocaine abusers
Rat studies with alcohol and the over expression of D2 receptors?
As the amount of D2 receptors in the brain increased, the amount of alcohol intake decreased - consumed very little
High levels = decreased preference for the drug
What are some interesting findings in IMPULSIVE rats?
They were found to have low dopamine D2 receptors
They also escalated to increased levels of self, they lose control - may be correlated with obtaining addiction -administration more than non-impulsive rats
What is reduced dopamine transmission in the brain referred to as?
Hypodopaminergia
- Depressive like symptoms
- An inability or difficulty with experiencing pleasure
How can hypodopaminergia be elicited in animals?
A drug called reserpine
What is the inability to experience pleasure called?
Anhedonia - very typical symptom in addiciton
What does hypofrontality impair?
Compromises planning and decision making - this is seen in those addicted to drugs
How do dopamine D2 receptor levels influence the vulnerability of drug addiction?
High dopamine D2 receptors = more likely to report the effects of drugs such as methylphenidate as not pleasant
Low dopamine D2 receptors = more likely to report the effects of the drug as pleasant
Rat studies with alcohol and the over expression of D2 receptors?
As the amount of D2 receptors in the brain increased, the amount of alcohol intake decreased
What are some interesting findings in impulsive rats?
They were found to have low dopamine D2 receptors
They also escalated to increased levels of self-administration more than non-impulsive rats
What else are low levels of dopamine D2 receptors associated with?
Decreased activity (metabolism) in the orbitofrontal cortex - This is an area involved in controlling behaviour and impulse control (could be why we see deficits)
Explain LTP and NMDA and AMPA receptors
NMDA receptors are occupied by glutamate
These NMDA channels open slightly to allow calcium into the cell
But these channels are blocked by magnesium
Magnesium can be removed by stimulation of AMPA receptors
- these allow sodium into the cell, depolarises the membrane and dislodges the magnesium in the NMDA receptor
- more AMPA are created, makes the cell more sensititve
