Neurophysiology of reward and addiction Flashcards
what is motivation
a process that mediates goal-directed responses or goal seeking behavior to change in the external or internal environment
What is reinforcement
the consequence of operant (learned) behaviors that alters the probability that a behavior will be repeated under similar conditions each time
whaet is saliency
something important in the surrounding environment worth paying attention to
What is a reward
objects, stimuli, or activities that have positive value
What is aversion
a negative reinforcement of behavior that the individual will learn to avoid future encounters
What is pleasure
a positive sensation often referred to as euphoria or hedonia
promotes behaviors that are consistent with survival of self and the species
What is the difference between an unpredicted reward and a predicted reward and the issues with repeated drug use
An unpredicted reward elicts an activation (positive prediction error)
a fully predicted reward elicts no response
omission of a predicted reward induces a depression
over repeated drug use, the repetition of these reward prediction error (RPE) signals would continue to reinforce drug related cues and behaviors
this is contrast to natural rewards that produce error correcting DA-RPE signals only until the predictions match actual events
as a result when given the choice between drug and natural reward, the individual develops a bias towards drug that strengthens with each drug use
Effects of drugs on dopamine
Drugs of abuse increase extracellular dopamine concentrations in limbic regions including the nucleus accumbens (NA)
produce longer and larger increases in dopamine
Cocaine, amphetamine, methamphetamine, and ecstsy increase dopamine by inhibiting dopamine reuptake
nicotine, alcohol, opiates, and marijuana work indirectly on neurons that modulate dopamine levels
drugs also affects the salience making the environment more pleasurable and arousing as well
What is the basic circuit of the mesolimbic system
main purpose of the Nucleus accumbens is the suppress sensations of pleasure therefore by default the NA is constiently activated from the hippocampus amygdala and prefrontal cortex via the neurotransmitter Glutamate
NA contains GABA neurons that synapse on to the pre frontal cortex keeping the brain at a reward neutral state
What is the reward circuit of the mesolimbic system
When something elicts a reward the Ventral tegmental area becomes activated which inhibits the NA
Dopamine from the ventral tegmental area project to the NA
Dopamine is released into the NA
Dopamine inhibits the NA and therefore the NA activity decreases
this then allows for activation at the pre frontal cortex leading to a sensation of pleasure
this is called the dopamine-hypothesis of reward
How does the Ventral Tegmental Area become activated
The VTA is activated by excitatoryneuro transmitters (EAA) orexin or acetylcholine
these arise from the Dorsal tegmental area (ach) the pre-frontal cortex (EAA) and the hypothalamus (orexin)
The reward feedback circuit
Projections from the NA back to the Ventral tegmental area that inhibit the VTA since they are GABA neurons
the NA will also release a co transmitter called dynorphin, this opioid will bind the kappa opioid receptor in the VTA and help supress additional release of dopamine from the VTA to halt the reward process
How can the VTA be activated via opioids
Exercise, ethanol, and other activities can release endogenous opioid signaling at all levels of the reward network: THe VTA, NA and PFC
this activation is done on mu receptors that activate dopamine neurons in the VTA
this is done by disinhibiting local VTA interneurons that suppress the dopaminergic activity
it will also activate local interneurons in the NA and inhibit the GABA neurons in the NA
also will activate the PFC its self
all this leads to a profound amount of euphoria/pleasure
called the dopamine independant reward pathway
what plays a major factor in the addictive behaviors caused by a drug
Chronic drug exposure alters the morphology of neurons in dopamine regulated circuits
can affect expression of certain transcription factors and nuclear proteins binding to regulatory regions
this has been noted for all neurotransmitters not dust dopamine
people with addictions have shown to have abnormal levels of neurotransmitter levels in the mesocortical region including the orbitofrontal cortex and the the cingulate gyrus important in compulsive behaviors and regulation of disinhibition
Role of memory with drug addiction
A lasting memory is created that associates good feelings with the circumstances of the environment in which it occured
these memories called conditioned associations also utilize the cravings (amygdala) when the abuser encounters those persons or things and is then driven to make a poor decision or seek out more drugs
a strong repeated stimulation increases the phosphorylation of the AMPA receptors and insertion of additional AMPA receptors into the post synaptic membrane
leads to activation of the calcium calmodulin CREB mechanism
within NA the target is dynorphin
Physical dependency of the drug
Excessive noradrenergic output from the locus ceruleus and CREB dependant upregulation of target genes in the locus ceruleus
change in FosB and AP-1 genes shown to be upregulated by stress and drugs of abuse
these upregulate the expression of EAA receptors
upregulates the cell signal transduction pathways
and factors promoting drug seeking motivation and locomotion
How does conditioning play a factor in addiction relapse
dopamine increases induced by drugs can induce associative learning (conditioning)
this triggers phasic Dopamine firing in the VTA resulting in fast large short lived DA in the NA reflecting expectation of a reward
therefore conditioned responses prvide powerful cues to drug taking in specific social circumstances and is then reinforced by the drug taking process
How does fear play a role in the conditioning of an addiction relapse
Conditioned fear of drug withdrawal effects can become a cue to use the drug
conditioning of the dopamine intake can lead to prevention of a conditioned fear
Non addicted brain
the saliency of substance and substances cues are low because the brin inhibits the drive to seek the substances
conditioned cues have little to no influence in the saliency of the drug substances
the saliency of the natural rewards greatly overrides the saliency of drugs
Addicted brain
the saliency of the substance and substance related cues is increased
this overrides the PFCs control of behavior and can no longer inhibit the drive to seek the substance
conditioned cues reinforce the substance seeking behavior
the saliency of substances overrides the saliency of natural rewards which no longer influence behavior
Summary of dopamine modulation in key brain regions: Amygdala
retrieval of fear memories
Summary of dopamine modulation in key brain regions: Ventral tegmental area
signals prediction error between expected outcome and actual reward experienced
Summary of dopamine modulation in key brain regions: Nucleus accumbens
assignment of saliency to certain stimuli and mediate decisions that seek or avoid a desirable situation
acute stress, corticotropin releasing factor CRF usually increases dopamine relese in the NA in short term
prolonged chronic stress results in CRF inducing a dopamine release that was once associated with pleassurable appetitive results
Summary of dopamine modulation in key brain regions: hippocampus
provides place and direction contextual information about the environment in which the stimuli os experience
Summary of dopamine modulation in key brain regions: substantia nigra and dorsal striatum
motor response associated with navigating the environment toward the desirable cue with a goal of engaging the activity
