10.1 Neurophysiology of Reward and Addiction Flashcards
Motivation is a process that mediates goal-directed responses or goal-seeking behavior to changes in the _______ or _______ _______.
external; internal environment
Reinforcement is the consequence of operant/learned behaviors that ______ ____ ______ that a behavior will be ______ under similar conditions each time.
alters the probability; repeated
Saliency is something important in the _____ ______ worth paying attention to.
surrounding environment
What is a reward?
Objects, stimuli, or activities that have positive value.
Aversion is a ______ reinforcement of behavior that the individual will learn to ____ in future encounters.
negative; avoid
Pleasure is a _____ sensation often referred to as ______ or ______.
positive; eupohore; hedonia
The physiologic purpose of pleasure is to promote behaviors that are consistent with _____ __ ____ and the _____.
survival of self; species
What are natural rewards elicited by?
caring for young, palatable food, mating, and exercise
______ neurons encode the discrepancy between reward predictions and information about the actual reward received and broadcast the signal downstream to reward centers in the brain.
Dopaminergic
An unpredicted reward elicits an activation called a ______ ______ ______.
positive prediction error
A fully predicted reward elicits _____ _____.
no response
Omission of a predicted reward elicits a ______.
depression
Over repeated drug use, the repetition of reward prediction error (RPE) signals would ______ drug-related cues and behaviors.
reinforce
_______ _______ produce error-correcting DA-RPE signals only until the predictions match the actual events.
Natural rewards
_______ is associated with the reinforcing effects of most drugs of abuse.
Dopamine
Drugs of abuse increase _______ _______ concentrations in limbic regions, including the nucleus accumbens.
extracellular dopamine
Drugs of abuse provide _____ and _____ increases in dopamine than natural reinforces such as food and sex.
longer; larger
Which drugs increase dopamine directly?
cocaine, amphetamine, methamphetamine, and ecstasy
Which drugs increase dopamine indirectly via other neuron receptors?
nicotine, alcohol, opiates, and marijuana
Salience refers to a stimuli or environmental changes that are ______ or elicit an ______-______ switch.
arousing; attentional-behavioral
Salience affects the ______ to seek an anticipated reward and facilitates _____ _____.
motivation; conditioned learning
Because dopamine is involved in the _____ of reward and ______, drug-induced increases in dopamine will inherently motivate further procurement of more drug, regardless or whether or not the effects of the drug are perceived as pleasurable.
prediction; salience
Salience leads to a situation in which _____ _____ associated with the drug can increase dopamine themselves and elicit the desire for the drug.
sensory stimuli
What does the mesolimbic system consist of?
nucleus accumbens, ventral tegmental area (VTA), limbic system, and pre-frontal cortex
What are the important neurotransmitters in the mesolimbic system?
dopamine, GABA, opioids, EAAs, dynorphin, and orexin
The main function of the nucleus accumbens is to _____ sensations of pleasure/reward.
suppress
The nucleus accumbens is _______ ______ by a constant trickle of EAAs like glutamate.
constitutively activated
The nucleus accumbens neurons are GABAergic meaning the activation of these neurons stimulate them to _____ _____.
release GABA
GABA is _____, so stimulation of nucleus accumbens neurons will _____ their target.
inhibitory; inhibit
Constitutive inhibition of the pre-frontal cortex targets keeps the brain in a ______-_____ state.
reward-neutral
When you do something that elicits a reward, the _____ becomes activated.
ventral tegmental area (VTA)
Dopaminergic neurons from the VTA project to the _____ _____.
nucleus accumbens
Ultimately, when you do something that elicits a reward, the nucleus accumbens activity (releasing GABA & suppressing sensations of pleasure) is _____.
inhibited
Decreased nucleus accumbens activity (decreased GABA release) results in _______ ____ _______.
sensation of pleasure
The VTA is activated by ____, ____, or _____.
EAAs (glutamate); orexin; acetylcholine
The pre-frontal cortex releases ______.
EAAs (glutamate)
The dorsal tegmental area releases ______.
acetylcholine
The hypothalamus releases _____ and is activated by ______ ___ ____.
orexin; consumption of food
Nucleus accumbens neurons release ____ and _______.
GABA and dynorphin
Dynorphin is an _____ that binds to the ____-____ receptor in the VTA.
opioid; kappa-opioid
Together, GABA and dynorphin _____ the additional release of dopamine from the VTA as a means to ____ the reward process.
suppress; halt
The inactivation of the nucleus accumbens via dopaminergic neurons from the VTA is termed the ________-________ ____ ______.
dopamine-hypothesis of reward
Many drugs of abuse activate the ______ __-_____.
mesolimbic DA-system
Endogenous opioids activate the _____-_______ reward pathway.
dopamine-independent
Exercise, ethanol, and other activities increase endogenous opioid signaling at the ____, _____, and _____.
VTA; nucleus accumbens; pre-frontal cortex
Opioids activate ___-receptors which activate dopaminergic neurons in the VTA (via inhibiting local VTA interneurons which normally suppress dopaminergic activity), activate local interneurons in the nucleus accumbens (via inhibiting GABA-ergic neurons), and activate the pre-frontal cortex.
mu
Opioids _____ dopaminergic neurons in the VTA, allowing ______ dopamine in the nucleus accumbens, inhibiting GABA release, resulting in a profound sense of _____ via activation of the PFC.
disinhibit/activate; increased; pleasure
Compared to normal reward stimuli, rewards due to drugs of abuse are ______ to an otherwise mild stimulus because the dopamine signal in the nucleus accumbens is not proportional to the stimulus.
exaggerated
Chronic drug exposure alters the ______ of neurons in dopamine-related circuits.
morphology
Drugs have been reported to alter the expression of certain ______ _____ as well as a variety of proteins involved in neurotransmission.
transcription factors
What neurotransmitters have been documented to have addiction-related adaptations?
Dopamine, glutamate, GABA, opioids, serotonin, and various neuropeptides.
In people with addictions, abnormal neurotransmitter levels are found in the ________ region of the brain.
mesocortical
What does the mesocortical region of the brain include?
orbitofrontal cortex and cingulate cortex
The orbitofrontal cortex is involved in _____ _____.
compulsive behavior
The cingulate gyrus regulates ________.
disinhibition
What are conditioned associations?
A lasting memory that is created which associates good feelings with the circumstance and environment in which they occur.
Conditioned associations occur in the ______ and utilize circuitry which mediates _____ in the ______ when the abuser encounters the persons or things and is then driven to make poor decisions or seek out more drugs in spite of obstacles.
hippocampus; cravings; amygdala
Dynorphin feeds back from nucleus accumbens and helps to _____ dopaminergic signaling from the VTA.
suppress
The locus coeruleus is involved in _____ and ______.
arousal; vigilance
_____ ______ is due to excessive noradrenergic output from the locus coeruleus and CREB-dependent upregulation of target genes (dynorphin) in the locus coeruleus.
Physical dependency
DeltaFosB and AP-1 are upregulated by ____ and ____ ___ ____.
stress; drugs of abuse
______ and ____ upregulate expression of EAA receptor expression, elements of cell signal transduction pathways, and factors promoting drug seeking, motivation, and locomotion.
DeltaFosB and AP-1
Eventually, becoming _______ to fear drug withdrawal effects (which can be relieved by taking the drug) might lead to any source of stress or frustration becoming a ___ for drug use.
conditioned; cue
____ ______ is learning that one behavior is associated or leads to something unpleasant or aversive.
Fear conditioning
________ release within the reward circuit alters the subjective value assigned to fearful stimuli and directly affects memory consolidation.
Dopamine
Dopamine can alter the _____ through which fear occurs, alter the _____ itself, and/or alter the expression of the ______.
conditions; association; memory
In a non-addicted brain, the saliency of substances and substance cues should be ___.
low
In a non-addicted brain, conditioned cues have _____ to ____ influence on the saliency of drug-substances.
little; no
In a non-addicted brain, the saliency of natural rewards greatly ______ the saliency of drugs.
overrides
In an addicted brain, the saliency of substances and substance-related cues is _____.
increased
In an addicted brain, the pre-frontal cortex ____ _____ the drive to seek substances.
cannot inhibit
In an addicted brain, conditioned cues _____ the saliency of substances, further increasing _______-_______ behavior.
reinforce; substance-seeking
In an addicted brain, the saliency of substances ______ the saliency of natural rewards (which __ _____ influence behavior).
overrides; no longer
What does dopamine modulate in the amygdala?
retrieval of fear memories
Dopamine in the ______ signals prediction error between expected outcome and actual reward.
VTA
Dopamine in the ______ ______ modulates assignment of salience to certain stimuli and mediate decisions that seek (or avoid) a desirable (or aversive) situation.
nucleus accumbens
Acute stress (______ ______ ______) usually increases dopamine release in the nucleus accumbens in the short term.
corticotropin releasing factor (CRF)
______, ______, ______ stress results in CRF inducing a dopamine release. This causes dopamine to now be associated with ______ rather than pleasurable, appetitive results. This switches the _____ _____ to acute stressors.
prolonged; chronic; severe; aversion; emotional response
The _______ provides place and direction-contextual information about the environment in which stimuli are experienced.
hippocampus
Dopamine in the _____ _____ and _____ _____ causes a motor response associated with navigating the environment toward a desirable cue with the goal of engaging in the activity that elicits rewards.
substantia nigra; dorsal striatum
____-____ _______ is a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse.
long-term potentiation
In the ____ term, increased phosphorylation of ____ receptors and insertion of additional those receptors into the post-synaptic membrane of the locus coeruleus causes physical dependency.
short; AMPA
In the ____ term, ____-dependent upregulation of target genes involved in learning and memory causes physical dependency.
long; CREB
Activation of the calcium-calmodulin-CREB mechanism causes _______ _______ in the ____ term.
physical dependency; long
