Neurophysiology of Reward and Addiction Flashcards
Reward prediction error
- Dopaminergic neurons encode the mismatch b/w reward predicted and the info about the actual reward, then send this to brain regions involved in reward learning
1. Positive prediction error - unpredicted reward elicits an activation (brain arousal)
2. No response - fully predicted reward –> assigns value to reward itself rather than only noting when it occurred
3. Negative prediction error - omission of a predicted reward induces depression
Drug vs natural reward
- Repeated drug use causes repeated reward prediction error signals since the exogeneous compound elicits a larger and longer (5-10X) increase in extracellular [dopamine] in limbic regions than natural reinforcers (e.g. food and sex). These signals continue to reinforce drug-related cues and behaviors since we are unable to appropriately correct the reward prediction to this level
- Natural rewards produce an error-correcting dopamine reward prediction error that signals until the predictions match the actual events
Reward prediction and salience
- Salience = stimuli or environmental changes that are arousing or elicit an attentional-behavioral switch and it affects the motivation to seek anticipated reward + conditions learning –> drug-induced dopamine will motivate further drug procurement b/c salience and motivation to seek the drug becomes more powerful
- Also leads to an increase in DA via sensory stimuli associated w/ drug or drug taking to elicit desire for drug –> risk of relapse when exposed to familiar environment
Dopamine-hypothesis of reward
- Activation of the ventral tegmental area when engaging in behavior/activity that results in reward
- Dopaminergic neurons from the ventral tegmental area project to the nucleus accumbens
- Dopamine inhibits nucleus accumbens –> decreased activity
- Decreased GABA released on the prefrontal cortex –> sensation of pleasure
- Nucleus accumbens projects back on to the ventral tegmental area and eventually releases GABA and dynorphin (acts through kappa-opioid receptors) to suppress the additional DA release from the VTA to halt reward process
main function of the nucleus accumbens
- Suppress sensations of pleasure/reward via GABA projections to constitutively inhibit the prefrontal cortex –> reward-neutral state
- Nucleus accumbens is constitutively activated by trickle of EAA from hippocampus, amygdala or prefrontal cortex
How does the ventral tegmental area become activated in reward pathway?
Upon engaging in behavior or activity that results in reward it can be activated by:
- EAA from pre-frontal cortex
- ACh from dorsal tegmental area
- Orexin from hypothalamus in consuming food
Dopamine-independent reward pathway
- Exercise, ethanol, etc increase endogenous opioid at all lvls of the reward network via activation of mu-receptors w/in:
1. Dopaminergic neurons in the ventral tegmental area –> inhibit local interneurons to ‘disinhibit’ DA neurons and allow for DA release
2. Local interneurons in the nucleus accumbens to inhibit GABA neurons locally
3. Prefrontal cortex - Net = profound sense of pleasure
Normal reward stimuli vs reward due to drugs of abuse: normal reward stimuli
- Caused by release of dopamine from ventral tegmental area
- Reinforces behaviors c/w health, longevity and don’t have immediate benefit
- Reward = sense of pleasure
Normal reward stimuli vs reward due to drugs of abuse: drugs of abuse
- Drugs enhance dopamine release from ventral tegmental area
- Dopamine signal in nucleus accumbens is not proportional to stimuli (constant negative reward prediction error)
- Reward = enhanced euphoria and exaggerated reward to an otherwise mild stimulus
Memory in reward/addiction: hippocampus
-Lasting memory created that associates rewarding feelings w/ circumstance/context and environment in which they occur (“conditioned associations”)
Memory in reward/addiction: amygdala
- retrieval of fear memories
- mediates cravings
Memory in reward/addiction: ventral tegmental area
-signal prediction error b/w expected outcome and actual reward experienced
Memory in reward/addiction: substantia nigra & dorsal striatum
-motor response associated w/ navigating environment toward desirable cue w/ goal of engaging in activity that elicits reward
Memory in reward/addiction: orbitofrontal cortex
-when abuser encounters associated persons or things and then driven to make poor decisions or seek out more drugs in spit of obstacles
Memory mechanisms in reward/addiction
- Persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse –> requires repeated strong stimulation (Papez circuit)
a. Short-term - increased phosphorylation of AMPA in post-synpatic membrane
b. Longer term - activation of Ca2+-Calmodulin-CREB mechanism (LTP)
c. Life long - signaling cascades involving deltaFosB and AP-1
