Neurobiology and neurochemistry of reward and addictive behaviours Flashcards
Humans engage in behaviours that are rewarding. The pleasurable feelings provide positive reinforcement, so that the behaviour is repeated to ensure we get the same reward again. There are 2 types of reward, natural and artificial. What do these both mean?
- natural = food, sex, water, affection
- artificial = drugs, gambling, alcohol
When we talk about substances and their misuse, there is a continuum as laid out below:
Drug Use Drug Misuse, Abuse Problematic / Hazardous Drug Use Harmful Use Dependent Use
What does drug use mean?
- any psychoactive recreational substance use/ experimental use
- smoking weed for example
When we talk about substances and their misuse, there is a continuum as laid out below:
Drug Use Drug Misuse, Abuse Problematic / Hazardous Drug Use Harmful Use Dependent Use
What does drug misuse/abuse mean?
- any unsanctioned recreational substance use
When we talk about substances and their misuse, there is a continuum as laid out below:
Drug Use Drug Misuse, Abuse Problematic / Hazardous Drug Use Harmful Use Dependent Use
What does Problematic / Hazardous Drug Use mean?
- use of a psychoactive substance at amounts or rates likely to lead to problems
- can be physical or psychological problems
When we talk about substances and their misuse, there is a continuum as laid out below:
Drug Use Drug Misuse, Abuse Problematic / Hazardous Drug Use Harmful Use Dependent Use
What does Harmful Use mean?
- use of a psychoactive substance which leads to harm whether to health, psychological well being, or socially; need not be dependent use
When we talk about substances and their misuse, there is a continuum as laid out below:
Drug Use Drug Misuse, Abuse Problematic / Hazardous Drug Use Harmful Use Dependent Use
What does Dependent Use?
- persistent uncontrolled drug use repeatedly leading to [multiple] harmful consequences
- drinking alcohol to stop themselves entering withdrawal
What does addiction mean?
1 - need more of a drug/stimulus to achieve same effects as previously
2 - continue using drug/stimulus despite being aware of the negative consequences
3 - stop taking the drug/stimulus as patient is aware of the negative consequences
4 - normal function of the body is impaired if drug/stimulus is stopped
2 - continue using drug/stimulus despite being aware of the negative consequences
- a compulsive behaviour
- despite negative effects, patient still gets pleasure/positive reward which provides positive reinforcement and behaviour is reinforcing (compulsion)
- loss of control in limiting intake
What is Tolerance, also referred to as a hyposensitisation syndrome?
1 - need more of a drug/stimulus to achieve same effects as previously
2 - continue using drug/stimulus despite being aware of the negative consequences
3 - stop taking the drug/stimulus as patient is aware of the negative consequences
4 - normal function of the body is impaired if drug/stimulus is stopped
1 - need more of a drug/stimulus to achieve same effects as previously
- patient does not respond to a substance in the same way, becoming tolerant
- patient seeks a higher dose or stronger drug for same effect
What is Dependence?
1 - need more of a drug/stimulus to achieve same effects as previously
2 - continue using drug/stimulus despite being aware of the negative consequences
3 - stop taking the drug/stimulus as patient is aware of the negative consequences
4 - normal function of the body is impaired if drug/stimulus is stopped
4 - normal function of the body is impaired if drug/stimulus is stopped
- can present with physiological symptoms (alcohol withdrawal)
When we talk about harm associated with substance abuse disorders, there are 3 main types; pain, dependence and social. What are the 3 types of pain?
1 - acute, subacute and chronic
2 - early, middle and late
3 - acute, chronic and intravenous drug user
3 - acute, chronic and intravenous drug user
- acute = harm following a single use of a substance/drug
- chronic = harm due to regular use of a substance/drug
- intravenous drug user =high rate of toxicity
When we talk about harm associated with substance abuse disorders, there are 3 main types; pain, dependence and social. What are the 3 types of dependence?
1 - acute, subacute and chronic
2 - pleasure intensity, tolerance and dependence, psychological addiction
3 - acute, chronic and intravenous drug user
2 - pleasure intensity, tolerance and dependence, psychological addiction
- intensity of pleasure = drugs that induce immediate euphoria
- tolerance and dependence = stronger drug dose required for euphoric effects
- psychological addiction = cravings for drug
When we talk about harm associated with substance abuse disorders, there are 3 main types; pain, dependence and social. What are the 3 types of social harm?
1 - acute, subacute and chronic
2 - pleasure intensity, tolerance and dependence, psychological addiction
3 - acute, chronic and intravenous drug user
4 - intoxication, social harms, cost to economy
4 - intoxication, social harms, cost to economy
- intoxication = harm to persons or property following single use
- social harms = destruction of a social circle (family, friends)
- cost to economy = unemployment, treatment in NHS
When we talk about the life cycle of addiction, we need to consider the timescale and the effects. The scale for both of these is:
- acute drug use
- chronic drug use
- short term abstinence
- long term abstinence
When we think about time scale, how do we apply the above to a timescale for the life cycle of addiction? (for example is chronic drug use days or minutes)
- acute drug use = minutes/hours
- chronic drug use =days/year
- short term abstinence = hours days
- long term abstinence = days/years
When we talk about the life cycle of addiction, we need to consider the timescale and the effects. The scale for both of these is:
- acute drug use
- chronic drug use
- short term abstinence
- long term abstinence
When we think about the effect, how do we apply the above to an effect for the life cycle of addiction?
- acute drug use = reward/replacement
- chronic drug use = tolerance/dependance
- short term abstinence = withdrawal (tremors, GI disorders)
- long term abstinence = cravings/relapse (synaptic re-modelling)
What is the mesolimbic pathway, also referred to as the reward pathway?
1 - a dopaminergic pathway in the brain involved in positive reinforcement
2 - a glutaminergic pathway in the brain involved in positive reinforcement
3 - a sertoninergic pathway in the brain involved in positive reinforcement
4 - a acetylcholinergis pathway in the brain involved in positive reinforcement
1 - a dopaminergic pathway in the brain involved in positive reinforcement
The Mesocorticolimbic pathway is considered to be part of the wider cortico-basal ganglia-thalamo-cortical loop [CBGTC]. What components of the brain make up the CBGTC?
1 - cortex, cerebellum, basal ganglia
2 - cortex, thalamus and brain stem
3 - cortex, brain stem and basal ganglia
4 - cortex, basal ganglia and thalamus
4 - cortex, basal ganglia and thalamus
What are positive and negative valenced emotions, which is involved in the mesocorticolimbic pathway?
- positive = intrinsic attractiveness/goodness
- negative = averseness/badness of an event, object, or situation
- essentially positive or negative emotions
What is the start of the mesolimbic pathway?
1 - ventral tegmental area
2 - substantia niagra
3 - pituitary gland
4 - hypothalamus
1 - ventral tegmental area
- nucleus accumbens (main dopamine nucleus)
- located in the midbrain
The ventral tegmental area (VTA), located in the midbrain is the start of the mesocorticolimbic pathway. What is the VTA?
- a group of neurons located close to the midline on the floor of the midbrain
The ventral tegmental area (VTA), located in the midbrain is the start of the mesocorticolimbic pathway. The VTA is a group of neurons located close to the midline on the floor of the midbrain. VTA is the start of the mesolimbic pathway, where does it travel to next?
1 - nucleus accumbens
2 - substantia niagra
3 - pituitary gland
4 - hypothalamus
1 - nucleus accumbens
What is the difference between the mesolimbic and mesocortical pathways?
- mesolimbic = middle (midbrain) and limbic systems
- mesocortical = middle (midbrain) and cortical regions (outer brain areas)
What is the cingulate gyrus?
- an arch-shaped bulging of the cerebral cortex
- located above the corpus callosum
- described as the limbic cortex (involved in emotions and memory), influences emotionally enhanced memories
The ventral tegmental area, nucleus accumbens, prefrontal cortex and the cingulate gyrus are all involved in the mesocorticolimbic pathway. What other 2 key subcortical structures are involved in brain?
1 - amygdala and hippocampus
2 - amygdala and thalamus
3 - brain stem and hippocampus
4 - amygdala and pons
1 - amygdala and hippocampus
The image below illustrates the normal pathway for reward and reinforcement based on natural reinforces, such as food and sex. Why is understanding this pathway important for addiction, tolerance and dependance?
- addictive drugs can hijack this system
- BUT worse they provide an even greater positive valence than natural rewards (greater positive feeling), meaning they may be more likely to increase the risk of them repeating this regularly
The Nucleus Accumbens, which is part of the mesocorticolimbic pathway is important in processing of cognitive processing of motivation and reward, such as pleasure and re-enforcement. What are a few examples of non-natural pathways that can activate the natural pathway for reward and reinforcement seen below?
- cannabis/weed
- opioids
- alcohol
When we think about the reinforcement system we are aware that there is direct reinforcement from a stimulus, where something good has just occurred and we learn from this experience, and we are more likely to do this again. This is then able to strengthen neural connections between neurons detecting the stimulus and the neurons that produce the instrumental response, called long term potentiation. This is called associative learning (like with the dog, food, bell and saliva). Using cocaine as an example, how does this work?
- patient takes cocaine in a nightclub
- patient then associated going to a nightclub with taking cocaine
- clinically important as if someone in remission from cocaine goes to a nightclub they are more likely to relapse
Dopamine D1 receptors are involved in long term potentiation through the modification of glutamatergic transmission, which then allows long term potentiation (essentially more glutaminergic receptors are located on the cells membrane). What does this do to the synapses on dendrite spines and branches?
1 - nothing
2 - dendrite number and length increases
3 - synaptic remodelling causing increased number of dendritic spines
4 - synaptic remodelling causing a decreased number of dendritic spines
3 - synaptic remodelling causing increased number of dendritic spines
- more dendritic spines increase the surface area to receive information)
Dopamine D1 receptors are involved in long term potentiation in cocaine addiction through the modification of glutamatergic transmission, which then allows long term potentiation. This causes synaptic remodelling (essentially means more dendritic spines that increase surface area to receive information). Even in abstinence do these changes just disappear and what is the importance of them remaining?
- dendritic spines remain for months following abstinence
- memories in these pathways can trigger relapse, hence why its so difficult to remain abstinent
What is the locus coeruleus, which in Latin means “blue spot”?
1 - nucleus in the pons of the brainstem responsible for dopamine synthesis
2 - nucleus in the pons of the brainstem responsible for the synthesis of norepinephrine
3 - nucleus in the pons of the brainstem responsible for the synthesis of corticol
4 - nucleus in the pons of the brainstem responsible for the synthesis of serotonin
2 - nucleus in the pons of the brainstem responsible for the synthesis of norepinephrine
- principal site for brain synthesis of norepinephrine
- involved in stress and panic (fight or flight response)
Patients who associate alcohol with a positive valence (which increases dopamine release) and associate with a feeling of reward when consumed will have increased dopamine release from where?
- ventral tegmental area signals to the nucleus accumbens to release dopamine
In acute alcohol use what would we expect to see in GABA-A and NMDA receptors?
- agonist at GABA-A receptors
- antagonist at NMDA receptors
- cells inhibited from firing
In chronic alcohol use what would we expect to see in GABA and NMDA receptors?
- down regulation of GABA-A receptors as alcohol is acting as an agonist so we dont need as many
- up-regulation of NMDA receptors as alcohol is an antagonist so we need more to increase sensitivity
- the increased NMDA receptors means the firing of NMDA receptors returns to a normal level as a compensatory mechanism
In a patient who has alcohol withdrawal what could we see and why?
- over excitation due to increased NMDA receptors
- alcohol was acting as an antagonist to NMDA receptors, without it they go into overdrive
- physical symptoms (agitation, tremors, confusion, seizures)
Alcohol acts as a suppressant by acting as an agonist of GABA-A. In acute alcohol ingestion alcohol is GABA-A is agonist and an antagonist for the glutamate NMDA receptors. What does this do to the patient?
- increases GABA binding to GABA-A receptors, reducing neuronal activity
- decreases glutamates ability to bind with NMDA receptors and decreasing neuronal activity
Alcohol acts as a suppressant by acting as an agonist of GABA-A. In chronic alcohol ingestion what does alcohol do to GABA-A and glutamate NMDA (bound with Mg+) receptors. What happens to the receptors and what does this do to the patient?
- down-regulates the number GABA-A receptors
- down regulation of GABA-A is to increase neuronal firing (leads to tolerance)
- up-regulation of glutamate NMDA receptors
- up-regulation of glutamate NMDA receptors is to increase neuronal firing above the suppression by GABA
