phys of reward Flashcards
what is the central tenet of reward?
dopamine is invlved in reward seeking behaviors
where can dopamine fibers go and how?
via VTA
to nucleus accumbens
hippocampus
amygdala
prefrontal cortex
what does hypothalamus do in the reward system?
initiates neuroendocrne and viceral responses to reward by integrating all inputs
what is motivation?
process that mediates goal directed responses
what is reinforcement?
consequnce of learned behaviors that alters probability that it will be repeated
what is saliency?
something important to pay attention to
what is reward
objects, stimuli that have positive value
what is aversion?
negative reinforcment of behavior, need to avoid
what is pleasure?
positive sensation that promotes behaviors that allow survival
what does DA have to do with pleasure?
encodes discrepancy between reward predictions and information about actual rewards
sends this info to brain regions involved with rewards learning
what does an unpredicted award do?
causes an activation
what does a predicted award do?
nothing
what if you dont get a predicted reward?
depression
whats assigns value to reward?
events that preceded delivery of reward
what happens with repeated drug use and rewards?
what happens to an individuals choices?
repetition of reward prediction error signals continues to reinforce drug related cues and behavior
develops bias towards drug that strengthens drug use
what happens with natural reward mecanism?
produce error correcting DA-RPE signals only until predictions match actual events
what do drugs of abuse do with DA? why is this relevant
increase extracellular DA concentrations, esp in limbic regions such as NA
provide longer and larder increases in DA than natural reinforcers
do drugs directly increase DA?
some do (amphetamine, meth, cocaine)
some work indirectly via neuron receptors (nicotine, alcohol, opiates)
how are DA and salience related?
drug induced increases in dopamine will make you look for more
stimuli associated with the drug can elicit desire for drug
this is why relapse happens!
what does mesolimbic system consist of ? what does it utilize
nucleus accumbens
VTA
limbic system
PFC
utilizes dopamine, but other thing too such as GABA
what is the main purpose of NA?
suppress sensation of pleasure/reward
how is NA activated?
constitutively by constant trickle of EAA like glutamate
what kind of neurons are NA? what do they do
gaba ergic, which causes them to inhibit their target, PFC
consitutitive inhibition of PFC keeps brain in reward neutral state
what happens when you do something to get a reward?
VTA get activated
how does the reward circuit work?
dopaminergic neurons from VTA go to A
DA released on NA
inhibits NA neurons
NA activity decreases
results in pleasure
how does VTA get activated?
activated by EAA from PFC
DTA (AcH)
or Hypothalamus (orexin)
what do NA do to VTA?
inhibit it via GABA
require dynorphin
stops reward process
what receptor does dynorphin bind to?
kappa opioid on VTA
explain reward feedback circuit
NA releases GABA on VTA
dynorphin is co transmitter
stops DA from being released by VTA
what can activate VTA via mu receptor?
exercise, ethanol, and other activities
how do EAA, Ach, orexin and opioids affect VTA? NA? PFC? what happens
inhibit local interneurons on VTA, disinhibit dopaminergic neurons
activate local interneurons of NA, inhibit gabaergic neurons
activate PFC
profound state of euphoria
how do drugs affect reward due to dopamine release?
can enhance dopamine release from VTA
how do drugs reinforce behavior that has no benefit?
dopamine signal in NA not proportional to stimuli
how do drugs cause reward for behavior to be sense of pleasure derived?
enhanced euphoria and exaggerated reward
how does addiction occur?
chronic drug exposure that alters morphology of neurons in dopamine related circuits
drugs alter expression of certain transcription factors at cellular level
also affect proteins involved with neurotransmission in brain region regulated by dopamine
what neurotransmitters are affected during addiction?
glutamate, gaba, opioids, serotonin
where re there abnormal neurotransmitter levels in addicted people brains?
what does this do
mesocortical region of the brain
plays role in aberrant behaviors such as poor inhibition and relapse
what does orbitofrontal cortex control?
involved in compulsive behavior
when abuser encounters certain persons or things
what does cingulate gyrus do?
regulates disinhibition
what creates lasting memories about good feelings and environment in which they occur?
hippocampus, uses circuitry that amygdala uses
what is amygdala used for?
circuitry for memories to mediate cravings
how can memory affect abusers?
seek out more drugs despite obstacles
what contributes to memory for abusers?
hippocampus
amygdala
orbitofrontal cortex
how is memory formed?
increase in synaptic strength
strong stimulation repeatedly
phosphorylaion of AMPA receptors and more AMPA receptors
activation of calcium-calmodulin-CREB
what does CREB do and where?
with NA, targes dynorphin
within LC: mediates physical dependency
returns to normal after drugs stop
how does physical dependency happen?
too much noradrenergic output from LC
CREB upregulation of genes in LC
what is FosB, what happens to it?
AP1*
upregulated by stress and drug abuse
upregulates EAA receptors
upregs cell signal transduction pathways
upregs factors promoting drug seeking
how long does it take for changes to FosB to occur?
months to years!
what induces associative learning?
sufficiently large DA, such as by drugs in NA
what does conditioning trigger?
phasic DA firing in VTA resulting in large, short lived increases of DA
reflects expectation of reward
whats te difference between drugs of abuse and natural reinforcers?
natural stop firing when event stops
drug abuse keeps firing
what do conditioned responses do?
provide cues to drug taking in specific circumstances
reinforced by aspects of the drug taking process
wat do drug addicted cues do in addicts?
elicits drug urges and physiological responses
activation of reward circuits
how does fearing drug withdrawal affect drug use?
becomes cue for drug use, conditioned to useto avoid witdrawal
what is fear conditioning?
learning that one behavior leads to something bad
what alters subjective value assigned to stimuli in circuit?
what does it do as a result
dopamine, affects memory consolidation
how can dopamine affect stimuli?
alter conditions thru which fear occurs
alter association itself
gives value to fearful stimuli
why can DA affect learned experiences so much?
so many dopamine receptors and cascade pathways
is conditioning relevant to many addictions?
yes
in the non addicted brain, explain saliency of substances and conditiioned cues
saliency of drugs is low
substance cues are low, brain inhibits drive to seek
substances
conditioned cues have no influence on saliency
in the addicted brain, explain saliency of substances and conditiioned cues
saliency of drugs is higher
overrides PFC control of behavior, cant inhibit drive to seek substances
conditioned cues reinforce saliency, increasing substance seekin behavior
saliency of substances overrides saliency of natural rewards
what does VTA do?
prediction error between expected outcome and actual reward
what does NA do?
salience to stimuli
mediate decisions that seek a desirable situation
what does hippocampus do?
place and direction contextual info about environement in which stimuli is experienced
what do substantia nigra and dorsal striatum do?
motor response associated with going towards desirable cue to elicit reward
acutre stress does what to DA?
increases DA release in NA
chronic stress does what with DA? why?
induces dopamine release that was one associated with pleasure, switches emotional response to acute stressors
divergent action between CRF1 and CRF2 receptors in NA
