Reward and Addiction Flashcards
Motivation
Use goal oriented responses and behavior to change external or internal environments
Reinforcement can be used to cause similar behaviors to occur
Salience
Something important that is worth paying attention to in the environment
“Wanting”
You notice a feature that indicate that good rewarding things can come from it
Reward
Involves
- Hedonic effect of pleasure
- Motivation to obtain reward because of its value(Salience)
- Associated learning
Aversion
Negative reinforcement of behavior to avoid future encounters
Pleasure/ Hedonia
Positive sensation, euphoria or hedonia “Liking”
Reward Production Error (RPE)
Dopamine neurons encode the discrepancy between reward prediction and what you actually get ——> brain regions for reward learning
Positive Prediction Reward Error
- Unpredicted reward is elicited (massive brain stimulation)
No RPE
Fully predicted reward is eliciting no reward(no RPE) so you get the reward you expected
Negative Prediction Error
Don’t get reward you expect —-> depression in stimulation
Drugs vs natural rewards
Drugs: have a continuous negative RPE which increases stimulation of brain and is therefore preferred Natural Rewards(caring for young, food, exercise, mating): they are error-correcting DA-RPE, so you get the reward you expect (you learn to predict the outcome)
Drug abuse increases what NT and where
Dopamine in ECM of the Nucleus Accumbens
Cause 5-10 times higher Dopamine then natural reinforcement like sex and food
Drugs increasing Dopamine directly
Cocaine, Amphetamine, Methamphetamine, and ecstasy ——I dopamine reuptake
——> dopamine release
Drugs indirectly increase Dopamine
drugs bind to neurons that regulate other neurons to release more dopamine
Nicotine, Alcohol, opiates, marijuana
how environment and stimuli elicits behavior change (SALIENCE)
How this works in drugs and the reason people relapse
Drugs release 5-10 times more dopamine = more motivation to find the drug or stimuli then natural reward= you have motivation even if you can’t consciously feel the pleasure (since dopamine still increases)
+
Salience and Dopamine increases with even the sight, sound…. of anything associated with the drug in the environment = elicit desire for the drug
Mesolithic System uses what NT
What 4 parts to it
Uses DOPAMINE
- NA-> GABA
- Ventral Tegmental area -> Opioids
- Limbic System -> Dynorphin
- PFC-> EAA
NA (Nucleus Accumbens) Function
The Basic Circuit
To suppress sensation of pleasure and reward
Is default activated continuously by some EAA(GLUTAMATE) from hippocampus, amygdala, or PFC
Stimulated NA neurons release GABA at the PFC which keeps the brain in a reward neutral state (no pleasure)
The reward circuit
The VTA is activated VTA Neurons release Dopamine on NA NA neurons are inhibited NA doesn’t release GABA on the PFC Sensation and pleasure is felt
What activated the VTA
Due to engaging behavior which results in reward innately
Or due to a drug in innately
EEA GLUTAMATE from the PFC
ACH from the Tegmental Nuclei like Dorsal Tegmental Area
OREXIN from the hypothalamus when eating food
The reward feed back to shut it off
Neurons from the NA go to the VTA releasing GABA ——I VTA
And releasing Dynorphin (opioid) ——I(binds kappa-opioid R) VTA
= inhibit dopamine release
Dopamine hypothesis of reward
Inactivation of NA by the VTA
Dopamine-Independent Reward Pathway
Exercise, alcohol, and other activities increase opioid at all levels= VTA, NA, PFC: (BIND TO mu- receptors)
- VTA = bind/activate VTA dopaminergic inhibiting interneurons to allow VTA to release Dopamine
- NA = bind/activate to NA GABA releasing interneurons to inhibit NA form releasing GABA
- PFC= activate it directly
Uses endogenous opioids, a lot of pleasure
Reward from drug
Causes dopamine signal to the NA that is not proportional to a stimuli
REWARD= enhanced euphoria and exaggerated reward to a mild stimulus
Not learned behavior
Reward from natural thing like exercise
Dopamine release from VTA to inhibit NA due to a specific stimulus like running
To promote healthy living that may not have immediate benefits
REWARD= sense of pleasure
Learned behavior
Chronic Drug use alters neurons at a cellular level
Changes expression of TF and proteins involved in neurotransmission to regulate dopamine release
Chronic Drug use alters neurons at a neurotransmitter level
Adapting to the stimulus from Dopamine, GABA, ,opioids, serotonin, and others
Hippocampus in reward to a drug
Conditioned associations
Lasting memory associating reward with circumstance and environment
Amygdala in reward form drug
Causes cravings
Orbitofrontal cortex in reward from drug
Person sees, hears, smells, associated things to drug they are driven to make bad decisions to get the drug despite obstacles
Learning and memory mechanisms
Continuous increase in synaptic strength following a high frequency stimulation of a chemical response
How is synaptic strength increased form memory and learning
- Short-term memory = phosphorylation of AMPA receptors in the post-synaptic membrane
- Long-term memory(days -years) = activated Ca+2-Calmodulin-CREB mechanism
- Life long memory= activate delta-FosB and AP-1 cascade
- Dynorphin can also cause memory
How does CREB work and where is it used to make memory
IN NA
In the NA
(Days-weeks) memory of reward stimulation
1.Ca+2 binds to Calmodulin
2. increase in cAMP—-> activate PKA
3. PKA activates CREB
4. CREB is a TF that goes to DNA to transcribe a lot of Dynorphin
How does CREB work and where is it used to make memory
In the Locus Ceruleus
For physical dependency
Due to excessive NorE causing CREB pathway
1.Ca+2 binds to Calmodulin
2. increase in cAMP—-> activate PKA
3. PKA activates CREB
4. CREB is a TF that goes to DNA to transcribe a lot of proteins for learning and memory in the Locus Ceruleus
delta-FosB and AP-1 are activated by what and cause what in their pathway
Life long learning
Drugs abuse, chronic stress….
Activates the delta-Fos-B and AP-1 cascade
They go to the DNA to transcribe structural proteins, EAA receptors, factors that increase motivation for seeking drug
Basic pathway of drug and its effects
- Drug binds to Ligand, voltage, or GPCR receptor
- 2nd messengers made which increase Ca+ or other messengers and cause cascade
- TF made
- Expression changes: BDNF (neural growth), Cytoskeleton, synapse and growth, NT synthesis, NT receptors
Dopamine release from the VTA with conditioning (learning)
Short, fast, large released
To expect reward
Stop firing after event concludes
Except drugs keep DA release
Fear conditioning
You feel the withdrawal effects after drug effects go away causing fear of withdrawal causing drug consumption
Role of dopamine in addiction
Causes change in memory and emotion to a stimuli
Attached a euphoric feeling to previously feared stimuli and attaches an excepted reward feeling to a stimuli
LEARNED CONDITIONING
Stress in the NA
NA assigns salience to certain stimuli and make us seek that or avoid that
ACUTE STRESS= Corticotrophin releasing factor (CRF) causes DOPAMINE to get released in the NA (short-term)
SEVERE, CHRONIC STRESS= CRF causes DOPAMINE increase causing aversive results now, not pleasurable
They act on different CRF receptors causing different results from dopamine
VTA in reward
Signals the prediction error
Hippocampus in reward
Provides place and direction information about the stimuli you experienced
Substantia Nigra and Dorsal Striatum in reward
Motor response to navigate environment toward the desire with goal to get the reward
Amygdala in reward
Retrieves memories of fear and fear conditioning
Non- addicted brain
- Saliency to something cues are low (brain inhibits drive to seek substances=all areas)
- Learned/conditioned cues have little or no influence on the saliency of the drug
- Saliency of natural rewards»_space;> saliency of drugs
Addicted brain
- The saliency of stimuli or substance is increased and HIGH
- The PFC can’t control behavior or inhibit drive to seek the substance
- Learned/conditioned cues increase saliency of substance -> increasing seeking it more
- Saliency of drug»_space;> natural rewards that don’t influence behavior anymore
