Neurophysiology of Reward and Addiction Flashcards
what is salience?
something important in the surrounding environment worth paying attention to; think of salience as “wanting”
what does it mean when something has salience?
it has value to an individual
what does reward involve?
hedonic (euphoric) effect of pleasure, motivation to obtain the reward because of its salience, and associated learning
what is aversion?
a negative reinforcement of behavior that the individual will learn to avoid future encounters
what is anhedonia?
lack of interest in something; no longer liking something previously liked- prominent feature in depression
an unpredicted award elicits what?
a positive prediction error
a fully predicted reward elicits what?
no response- no discrepancy associated with it
omission of a predicted reward induces what?
a depression (negative prediction error)
why is reward prediction error important?
it is going to highlight the difference between expected rewards and the experiences that induce either the expectation, omission, or fully-predicted value
drugs of abuse increase what?
extracellular dopamine concentrations in limbic regions, including the nucleus accumbens
what are some examples of drugs that increase dopamine directly?
cocaine, amphetamine, methamphetamine, and ecstasy
how do some drugs increase dopamine directly?
by inhibiting dopamine reuptake or promoting dopamine release
what are some drugs that increase dopamine indirectly?
nicotine, alcohol, opiates, and marijuana
what does salience affect?
the motivation to seek the anticipated reward and it facilitates conditioned learning
what are the effects of sensory stimuli associated with salience?
the sensory stimuli (sights or sounds) that are associated with salience (a drug or drug taking) can increase dopamine by themselves and elicit the desire for the drug
what is the important system involved in the neurophysilogic system of reward?
the mesolimbic system
what is the mesolimbic system made up of?
the nucleus accumbens, the ventral tegmental area, the prefrontal cortex, and the limbic system
what is the main function of the nucleus accumbens?
to suppress sensations of pleasure and reward
what type of neurons are nucleus accumbens neurons?
they are gabaergic
what is the nucleus accumbens constitutively being activated by?
a constant trickle of EAA like glutamate from the hippocampus, amygdala, or the pre-frontal cortex
what happens when the nucleus accumbens is activated?
they will be stimulated to release GABA upon their target
where do the GABAergic nucleus accumbens neurons project to and release GABA when stimulated?
the pre-frontal cortex
what is the effect of a constitutive inhibition of the PFC targets?
it keeps the brain in a reward-neutral state (no pleasure sensed)
what brain areas activate the nucleus accumbens?
hippocampus, amygdala, the PFC
when you do something that elicits a reward, what becomes activated?
the ventral tegmental area
what is the role of the ventral tegmental area?
it sends projects to the nucleus accumbens and turns it off
what is our main reward NT?
dopamine
what happens when the ventral tegmental area projects to the nucleus accumbens and releases dopamine?
the dopamine will inhibit the neurons in the nucleus accumbens
what happens when we have an inhibited nucleus accumbens/ nucleus accumbens activity decreases?
sensation of pleasure
How is the ventral tegmental area even activated??
upon engaging in behavior or activity that results in reward, the VTA is activated by EAA, orexin, or acetylcholine
where does orexin come from?
the hypothalamus
what areas activate the ventral tegmental area?
the prefrontal cortex, the hypothalamus, or the dorsal tegmental area
how do we shut the reward system off?
the reward feedback circuit- there are projections from the NA back to the ventral tegmental area
in addition to releasing GABA, the NA-neurons also release a co-transmitter called what?
dynorphin
what is dynorphin?
it is an opioid
what does dynorphin bind to?
the kappa-opiod receptor in the VTA
what do GABA and dynorphin function to do?
suppress additional release of dopamine from the VTA as a means to halt the reward process
what is the dopamine-hypothesis of reward?
the inactivation of the nucleus accumbens via the dopaminergic neurons from the VTA
what is the dopamine-independent reward pathway?
it utilizes endogenous opioids to obtain a profound sense of pleasure
How do opioids increase dopamine in the VTA?
by inhibitoon of GABAergic neurons locally through mu-receptors
Chronic drug exposure alters what?
the morphology of neurons in dopamine-regulated circuits
at a cellular level, what do drugs alter?
the expression of certain transcription factors
what is responsible for the conditioning?
hippocampus
what mediates craving?
the amygdala
when the abuser encounters the associated persons or things and is then driven to make poor decisions or seek out more drugs in spite of obstacles- what is responsible for this?
the orbitofrontal cortex
what is the mechanism of short term memory associated with reward and addiction?
increased phosphorylation of AMPA receptors in the post-synpatic membrane
what is the mechanism of longer term memory associated with reward and addiction?
activation of calcium-calmodulin-CREB mechanism
what is the mechanism of life-long memory associated with reward and addiction?
signaling cascades involving delta FosB and AP-1
what is one example of a target of the calcium-calmodulin CREB mechanism?
within the NA, a priminent target is dynorphin
what does CREB do>
it targets DNA to increase the transcription/translation of its target
what does the locus ceruleus mediate?
physical dependency
what mechanism targets the locus ceruleus?
CREB
what two transcription factors have life-long implications?
delta FosB and Ap-1
what are some targets of the deltaFos B and AP-1 transcription factors?
structural proteins, EAA receptor expression, and factors promoting drug seeking, motivation, and locomotion
