Physiology of Reward and Addiction Flashcards
(19 cards)
What is the key neurotransmitter in reward pathways?
Dopamine
Draw the dopaminergic projections of VTA to other parts of the brain
Ok
Motivation Saliency Reward Aversion Pleasure
- mediates goal directed behavior
- something important in the envt worth paying attention to
- objects that have positive value
- something negative that you try to avoid in the future
- positive sensation - euphoria, hedonia
How do DA neurons play a role in rewards pathway?
Compare sought reward vs. what reward you got and tell other reward structures this (reward prediction error)
What signals do DA neurons give to downstream reward circuit when…
Unpredicted reward
Predicted reward
No reward
- activation (+ prediction error)
- no response
- depression (- prediction error)
What is different about drugs of addiction vs natural rewards?
In drugs, DA RPE does not stop producing dopamine after you get your reward > reinforce drug related behavior > develop preference for drug reward over natural reward
How do dopamine and salience relate to each other?
Dopamine is involved in development of salience and affects conditioned learning to seek more of the drug. Salience also affects how a person responds to exposure to things about the drug (relapsing)
What is the normal function of the nucleus accumbens?
Suppress sensations of pleasure/reward. Need NA to be active to avoid addiction
Draw the basic (inactivated) reward circuit
OK
Draw the activated reward circuit (when you get a reward)
oK
How does the reward circuit get activated?
VTA is activated when you get a reward > VTA releases dopamine > dopamine inhibits NA > decrease in GABA inhibiting the PFC to seek and experience pleasure
How is the reward circuit regulated?
NA feedbacks to VTA by releasing GABA and an opioid called dynorphin. This is supposed to halt the release of more dopamine.
What is another way to activate the reward circuit?
Dopamine independent pathway. EAA, Ach, orexin and opoiods can bind mu-receptors and activate VTA and increase dopamine release. VTA will activate NA inhibitors so the NA is inactivated.
So how does addiction actually happen?
Chronic exposure to drug (reward) alters the morphology of the neurons in the reward circuit (synapses, TFs, NTs etc.)
What part of the brain is believed to play a role in development of addictive behavior?
Mesocortical brain region that contains the orbitofrontal cortex and cingulate gyrus, which are responsible for compulsive behavior and regulating disinhibition respectively. Alterations here related to compulsive drug seeking and poor inhibitory control.
How does memory play a role in drug abuse?
Things/events related to drug encoded in hippocampus and can activate the amygdala when encountering things related to drug (crave the drug when you are at a place you last consumed it)
How does a relapse physiologically occur?
Repeated strong stimulation by drug > AMPA phosphorylation and increased number of AMPA receptors on neurons > CREB mechanism activation
What is CREB and what are its targets?
Targets and inhibits dynorphin in NA
Mediates physical dependency in locus coeruleus
How is physical dependence induced?
CREB upregulates target genes (FosB and AP-1) during drug abuse. Upregulation of these genes increase EAA receptor activity and cause long term structural changes to neurons.
