Neurophysiology of Reward and Addiction (Pierce) Flashcards
- process that mediates goal-directed responses or goal-seeking behavior to changes in exeternal/internal environment
- reinforcement: consequence of operant behaviors that alters probability that behavior will be repeated under similar conditions each time
motivation
- something important in surrounding environment worth paying attention to
- attention-grabbing feature of rewarding objects
- heightens perception and focuses attention toward the particular sights, sounds, and smells associated with these rewards in a way that normally promotes well-being and survival
- triggered by encounters with reward-related cues and experienced as surges of motivation to obtain and consume the reward that can last beyond the time the individual is exposed to the cue
- something that has value to the individual so they want it
- can make the cues a/w drug use wanted almost as much as drug itself
salience
involves
1) hedonic effect of pleasure
2) motivation to obtain reward b/c its value (salience)
3) associated learning
reward
negative reinforcement of behavior that the individual will learn to avoid future encounters
aversion
- subjectively positive sensation often referred to as euphoria
- think of as “liking” something
pleasure/hedonia
What is the physiological purpose of pleasure?
- to promote behaviors that are c/w survival of self/species
- natural rewards elicited by behaviors may include caring for young, palatable food, mating, exercise/activity
- lack of interest, or no longer liking something previously liked
- component of depression
anhedonia
What neurons encode the discrepancy between reward predictions and info about actual reward received and send signal to the brain regions involved in reward learning?
dopaminergic (DA) neurons
- mismatch between events and reward elicited
- positive: unpredicted reward elicits an activation
- negative: omission of a predicted reward induces depression
- neutral: full predicted reward elicits no response (events that reliably precede reward delivery assigns value to reward itself, rather than just registering when reward has occurred)
reward prediction error (RPE)
What are the differences between drug and natural reward predictions and what do these differences lead to?
- repeated drug use: repetition of RPE signals continues to reinforce drug-related cues/behaviors
- natural rewards: produce error-correcting DA-RPE signals only until predictions match actual events
- result: when given a choice between state leading to drug or state leading to natural reward, individual develops bias toward drugs that strengthens w/ each use
- increase extracellular dopamine conc in limbic regions, including nucleus accumbens (NA)
- provide longer and larger (5-10x) increases in dopamine than natural reinforcers such as food or sex
- some increase dopamine directly (inhibit uptake or promote release) and some indirectly (other neuron receptors that modulate dopamine levels)
drugs of abuse
What is the relationship between reward prediction, salience, and dopamine?
- salience affects motivation to seek anticipated reward and facilitates conditioned learning
- suggests: drug-induced increases in dopamine will inherently motivate further procurement of more drugs (regardless of whether the effects of drug are consciously perceived to be pleasurable)
- salience also leads to situation where sensory stimuli a/w drug/drug intake can increase dopamine by themselves and elicit desire for drug (explains why addicted persons are more at risk of relapsing when exposed to an environment where they had previously taken the drug)
What are the important brain regions and NT’s a/w reward/addiction?
- mesolimbic system, dopamine
- nucleus accumbens (NA), GABA
- ventral tegmental area (VTA), opioids
- prefrontal cortex (PFA), EAA’s (glutamate)
- limbic system, dynorphin and orexin
What is the pathway for the reward-neutral state (no pleasure sensed)?
- main function of NA is to suppress sensations of pleasure/reward
- by default, it is constitutively activated by constant trickle of EAA’s (glutamate) from hippocampus, amygdala, or PFC
- NA neurons are GABAnergic (inhibitory), thus they inhibit their target regions, in this case they project to PFC
- constitutive inhibition of PFC targets keeps brain in reward-neutral state
What is the pathway for the reward state (pleasure sensed)?
- TLDR: VTA becomes activated and inhibits NA
1. DA neurons from VTA project to NA
2. DA is released into NA
3. DA inhibits neurons in NA
4. NA activity decreases
5. decreased NA activity results in sensation of pleasure (target areas in PFC are no longer inhibited)
In the reward-circuit, how is VTA activated in the first place?
by behavior/activity that results in reward VTA is activated by EAA’s (PFC), acetylcholine (other tegmental nuclei like dorsal tegmental area), and orexin (hypothalamus w/ food consumption)
How is the reward process halted within the reward-circuit?
- NA has projections back to the VTA
- NA sends GABAnergic neurons to VTA as well as neurons that release co-transmitter, dynorphin (opioid, binds kappa-opioid receptor in VTA)
- both GABA and dynorphin function to suppress additional release of dopamine from VTA to halt the reward process
- exercise, ethanol, and other activities increase endogenous opioid signaling at all levels of reward network (VTA, NA, PFC)
- via activation of mu-receptors, opioids activate: 1) dopaminergic neurons in VTA, 2) local interneurons in NA (inhibit GABAergic neurons locally), 3) the PFC itself
- net result: profound euphoria
dopamine-independent reward pathway
Describe calcium-calmodulin-CREB mechanism in terms of moderate-term addiction:
- Ca2+ binds to calmodulin > activates cAMP > activates PKA > activates CREB (transcription factor) > alters DNA within nucleus > produces more dynorphin
- faily short acting (days-weeks) and returns to normal levels after cessation of rewarding stimulus
Describe calcium-calmodulin-CREB mechanism in terms of locus ceruleus:
- within locus ceruleus calcium-calmodulin-CREB mechanism mediates physical dependency
- LC has excessive noradrenergic output (involved in arousal and vigilance) and CREB-dependent upregulation of target genes in LC leads to increase in structural proteins involved in learning/memory
Describe ΔFosB and AP-1 system in terms of reward/addiction:
- these are transcription factors that, when altered by drugs, can have lifelong (permanent) implications in terms of addiction
- mechanism: drugs of abuse, chronic stress, and other factors > trigger signaling cascades > ΔFosB and AP-1 > alter genes within nucleus > targets structural proteins, EAA receptor expression, elements of cell signal transduction pathways, and factors promoting drug seeking, motivation, and locomotion
