14) Reward and Addiction Flashcards
What are the 3 major dopaminergic pathways?
- Nigrostriatal system
- Mesolimbic system
- Mesocortical system
Carefully study image for more details
What is the primary reward circuit?
Where is its origin and terminal buttons?
Mesolimbic Pathway is the primary reward circuit in almost all organisms even invertebrates.
Origin = VTA
Terminal = Nucleus Accumbens (ventrial striatum)
Describe the 5 areas of the entire reward circuit
- Ventral Tegmental Area (VTA) - Source of DA cell bodies sending axon projections to the NA
- Nucleus Accumbens (NAc) receives DA inputs (axon terminals) from the VTA
- Basal Ganglia increases motor output to produce an overall increase in behavior
- Hippocampus tells the NAc where we are and what is happening around us (our context)
- Prefrontal Cortex provides the NAc with several options for behavior
What is reinforcement? What is its purpose?
What does the mesolimbic reward circuit normally direct/motivate?
Reinforcement = something that strengthens a behavior
The purpose of reinforcement is to create motivated behaviors.
The mesolimbic reward circuit normally directs/motivates behavior towards pursuit of natural rewards (sex, food, etc.) that increase DA release in NAc and away from non-rewarding behaviors (suppress DA release)
What is positive reinforcement? What is characteristic of this?
What is negative reinforcement?
Positive reinforcement = rewards introduced to increase a behavior
- Self-administration = animals will voluntarily push a lever to receive things that are positive reinforcers
Negative reinforcement = Punishment introduced to decrease a behavior
How do we know that positive reinforcement activates the mesolimbic pathway? (3)
- Natural rewards elevate DA release in the NAc
- measured with dialysis = fluid in/out
- Rats will self-administer electrical stimulation of the VTA -> NAc pathway
- DA neurons in the VTA change their activity patterns during reward learning
- When reward is predicted, but not delivered = VTA neural activity is suppressed
All drugs of abuse increase dopamine release in the NAc.
The way they do it differs.
How does nicotine do it? Cocaine and amphetamines? Opiates?
Nicotine
- Binds to ACh receptors on VTA neurons causing depolarization
- Increases glutamate release onto VTA neurons
- Both effects increase DA release from VTA nerons projecting to the NAc
Cocaine and Amphetamine
- Block DA reuptake into VTA axon terminals which increases the effect of DA in the NAc
Opiates
- Opioid receptors are inhibitory and present on GABA interneurons in the VTA
- Therefore decrease GABA release and inhibition of VTA neurons
- This disinhibits VTA neurons and increases dopamine release in the NAc
Start of addiction that leads to tolerance?
Pharmacodynamic tolerance (presynaptic) characteristics
What drugs?
- Blocks dopamine reuptake
- Causes large increases in dopamine release
Tolerance
- Continued high levels of synaptic dopamine activate dopamine autoreceptors on the presynaptic neuron
- Autoreceptor activation inhibits production of dopamine
- Eventually, the neuron becomes depleted of dopamine
Amphetamines and cocaine
Pharmacodynamic tolerance postsynaptic characteristics
Tolerance to drugs that mimic or amplify the actions of a neurotransmitter tends to decrease receptor activity
- Down-regulation - decrease in number of functional receptors
- Desensitization - decrease in receptors’ ability to elicit changes
Chronic drug abuse brain characteristics
- Lower D2 receptor expression
- Lower baseline DA release
- Creates blunted response to natural rewards and anhedonia
- Subjects dont feel ‘normal’ unless they have dopamine levels increased by their drug of choice
Drug treatment strategies
Psycho-social interventions (AA)
Medical interventions
- Decreases withdrawal symptoms
- Provide alternatives
- Block actions of drugs
- Alter the metabolism of the drug
- Block the brain’s reward system
Still high rates of relapse.
