Biology of Reward Flashcards
What is it important to remember about substance misuse?
That patients are individuals - the factors that drive patients to misuse substances are unique and individualised and should be treated as such.
What is better for substance misuse - treatment or prevention?
Prevention is better as treatment is high cost and chronic in nature
Why do humans like behaviours that are rewarding?
Pleasurable feelings from behaviour = positive reinforcement & positive valence = repetition of behaviour
What are the two types of rewards/highs?
Natural & artificial
What are examples of artificial highs?
Drugs, gambling, alcohol
What are examples of natural highs?
Food, sex, nurture & affection
What are the levels of the continuum of use?
- Drug Use
- Drug Misuse, Abuse
- Problematic / Hazardous Drug Use
- Harmful Use
- Dependant Use
What type of use is this?
Psychoactive recreational substance use / experimental use
Drug use
What type of use is this?
Any unsanctioned recreational substance use
Drug Misuse or Drug Abuse
What type of use is this?
Use of a psychoactive substance at amount of rate LIKELY to lead to problems
Problematic / Hazardous Drug Use
What type of use is this?
Use of a psychoactive substance which leads to harm whether to health, psychological well being or social (dont need to be dependent)
Harmful Use
What type of use is this?
Persistent uncontrolled drug use repeatedly leading to multiple harmful consequences
Dependent use
What is the following a definition of?
State in which a person engages in compulsive behaviour, even when aware of negative consequences. Behaviour is reinforcing. Loss of control in limiting intake.
Addiction
What is the following a definition of?
Person no longer responds to a substance - higher dose is required to achieve the same effect.
Tolerance
What is another term for tolerance?
Hyposensitisation syndrome
What is the following a definition of?
Person functions normally only in the presence of a drug, There is manifested physical homeostatic disturbance when the drug is removed.
Dependance
What is delirium tremens a sign of?
Alcohol withdrawal
What social harms can arise from substance misuse?
Damage to property, relationships, people, destruction of families, job loss, unemployment, policing implication and healthcare provision cost
Which type of dependance has the highest cost to society?
Opiod use - IVDU
How does acute drug use compare to chronic drug use in terms to definition?
Acute drug use = Minutes-hours of use
Chronic = days-years of use
What are then negative risks to chronic drug use?
Tolerance and dependance
What are the risks associated with short term abstinence?
Withdrawal (can be v dangerous)
What are the risks associated with long term abstinence?
Cravings & relapse
Which part of the brain is involved in developing addiction?
The mesocorticolimbic system
What is the mesocorticolimbic system part of?
The coptic-basal ganglia-thalamo-cortical loop (CBGTC)
Which is the key structure in the brain that mediates emotional and motivational processing inc pleasure?
Nucleus Accumbens [NAcc]
Which are the two pathways involved in the msocorticolimbic circuitry?
Mesolimbic pathway
Mesocortico pathway
Where does the mesolimbic pathway run from and to?
From ventral tegmental area to the cingulate gyrus
Where does the mesocortical pathway run?
From ventral tegmetal area to the pre-frontal cortex
Which central parts of the brain are involved with reward?
Amygdala & Hippocampus
What role does the pre-frontal cortex play in addiction?
Impulsiveness & decision making - important for long-term addiction
What does the nucleus accumbens release?
Dopamine
In terms of dopamine - why are artificial highs more addictive than natural highs?
They release more powerful and reliable activation = more dopamine released more regularly
What does blockade of dopamine release do?
Lessens the rewarding effects of addictive drugs
What does activation of the mesocorticolimbic pathways result in?
Release of extracellular dopamine release via the nucleus accumbens
What is a problem with long term abuse of substances in terms of natural highs?
P is used to euphoric artificial highs which are greater than natural highs - means they can face a lifetime of less happiness as a result
Which substances act directly on the nucleus accumbens?
Opioids, cannabinoids & alcohol
Which substances produce reward partly through non dopaminergic mechanisms?
Cannabinoids
Alcohol
Nicotine
Is the nucleus accumbens only stimulated by a substance?
No - can also be stimulated in anticipation of the reward
How does the brain reinforce positive valence?
Recognises something good has happened
Attaches positive valence to it
Strengthens the neural connections between neurons that detect stimulus and those that produce the response
What is the name for the strengthening of neural connections between stimulus detection and response?§
Long term potentiation
What describes the impact that the environment of misuse can have?
Associative learning
How do Ps get addicted?
Initial drug = released dopamine = reinforcement of the experience,.
However - tolerance increases, so increasing amounts of drugs are needed = dependance.
Homeostatic changes & neuronal adaptations
If a P successfully detoxes and abstains from drugs, but then relapses later - what is the risk?
That they will misjudge their tolerance (which has since decreased) and have higher chances of OD
Why is there a lifelong risk of relapse?
Due to associative learning from synaptic plasticity
What is psychosis?
A temporary detachment from reality, often with marked positive features (such as hallucinations)
Which NT do we think is involved in the positive symptoms of psychosis / schizophrenia?
Dopamine
What do anti-psychotics do?
Block or antagonise dopamine
What do cocaine and amphetamine do?
Cause changes molecularly and cellularly that promote dysregulation (e.g. inc activity in ventral tegmental area)
AND
Cause hypofrontality (decreased blood flow to pre-frontal cortex - cant think things through as well
How does dopamine enhance long term potentiation?
Modifies glutamateric transmission at D1 receptors - leading to synaptic remodelling by increased numbers of dendritic spines and branches
What is long term potentiation?
Strengthening of synapses based on recent activity
How long does long term potentiation last for?
Months - Years
What does long term potentiation mean for recovery?
Memories in these pathways may trigger relapses years later
How does cocaine affect D2 receptors?
Decreases the numbers of them (down regulates them)
What is the consequence of down regulated D2 receptors?
Less D2 = adverse impacts on classic condition (learning/memory) + decreased motivation.
What do opiates target?
Opiate receptors in the mesocorticolimbic circuits
Name one area of the brain which is most adversely affected by opiods?
Locus coeruleus
What does the locus coeruleus do?
Has noradrenergic nuclei - therefore responsible for attention, arousal & flight / fight response of ANS
What does chronic activation of opioid receptors do?
Activates homeostatic mechanisms - which compensate for the functional changes caused by chronic use. This allows locus coeruleus neurons to return to their normal firing rates.
This leads to tolerance and dependence.
What does acute opioid use do to neurons?
Acutely inhibits firing of the neurons in the locus coeruleus.
What happens to the locus coeruleus in acute withdrawal?
There is a substantial increase in LC firing (this is what causes the physical symptoms).
This increase triggers over activation of the autonomic nervous system.
What is the Kindling effect?
That withdrawal symptoms worsen with every repeated withdrawal
What is the best way to achieve complete abstinence and return to normal living?
Stepwise process - includes:
- motivating P
- involving them in the treatment plan
- minimise harms done in taking subtsances
- improve physical and mental health
- Reduce criminal activity
- reduce the rates of blood-born infections
- to stop substance use, and use safer alternative in short term if necessary
Use biopsychosocial approach
What receptors does alcohol affect?
GABA A (agonist)
NMDA (antagonist)
Therefore = depressive effects
Also inhibits the functioing of most voltage gated channels
What receptors does alcohol affect?
GABA A (agonist)
NMDA (antagonist)
Therefore = depressive effects
Also inhibits the functioning of most voltage gated channels
How does alcohol affect the nucleus accumbens?
Leads to increased dopamine release in the nucleus accumbens.
ALSO - inhibition of NMDA channels = disinhibits VTA dopaminergic neurons = increased dopamine release in the nucleus accumbens.
What is alcohol dependance syndrome?
Strong desire / compulsion to drink with difficulty refraining
Withdrawal when it is stopped
Evidence of tolerance (inc or dec)
Progressive loss of pleasure in alternative interests
Persistent use despite clear evidence of harm
What is the loss of pleasure called?
Anhedonia
What are the acute effects of alcohol?
Agonist of GABA A
Antagonist of NMDA
Cells inhibited from firing
What are the chronic effects of alcoho?
Downregulation of GABA A receptors
Upregulation of NMDA receptors
- Firing rates return to normal
What are the chronic effects of alcoho?
Downregulation of GABA A receptors
Upregulation of NMDA receptors
- Firing rates return to normal
What happens to receptors in withdrawal?
The balance shifts to excitation - lots of NMDA receptors allow Na to flow = lots of physical symptoms
What are the physical symptoms of alcohol withdrawal?
Agitation
Tremors
Confusion
Seizures
What are the treatment steps for alcohol dependence?
Assessment
Psychoeducation
Motivation for change
Safe withdrawal
Relapse prevention & treatment of underlying issues
Which drugs can be used for withdrawal of alcohol?
Benzodiazepines
Oral thiamine
Damage to which part of the brain can cause Wernicke’s?
Mamilliary bodies
