Lecture 3: Addiction and the Brain Flashcards
what is thought to happen to the reward pathway when exposed to drugs of abuse?
reward pathway is there for survival increase to prompt an animal to repeat rewarded behaviours
this pathway gets hijacked by drugs of abuse
what does the strength of reinforcing property correlate with?
correlates with addiction potential of drugs… i.e. the addiction potential of heroin is high, therefore it has stronger reinforcing potential as compared to LSD and vice versa
what is an example of an animal model of reinforcement?
includes a rat in a box
everytime the rat presses a level, a drug will be given to the rat
if the drug is rewarding then the rat will keep pressing the lever to receive more drug (increase in frequency)
this method can also be modified so drug injected can be systematic or in specific brain regions
the harder the animal works to get the drug the more reinforcing it will be
what are two schedules of drug administration used to give drugs to animal models?
- fixed ratio schedule: animal is required to perform behaviour a specific number of times to achieve the reward …. drug is given everytime a task is done
- progressive-ratio schedule: animal is required to perform and increasing number of responses for subsequent reward i.e. 1, 2,4,8 etc.. so the number of times the animal has to perform will increase everytime they get the drug. So the animal will be working for the drug more… the more reinforcing the drug is, the harder the animal will work to get it. So if the drug isnt that reinforcing, the animal will likely stop after 2 or 4 time sof performing the task and not getting a reward. Theres a quicker break point (time where animal stops trying) if drug isnt reinforcing.
what is extinction?
reducing the drug seeking behaviour to zero by removing the reward and drug in general
What are some activities in humans that can affect self administration?
- presence of an alternative stimuli like high quality food, exercise equipment
- drug history
- gender
- environment (enriched enviroments can reduce risks of drug taking behaviour)
what is the reinstatement paradigm? what does it measure?
the reinstatement paradigm measures vulnerability to relapse into drug abuse
in this paradigm, animals are trained to self administer
the behaviour is then extinguished by discontinuing the delivery of the drug, then the animal eventually gives up on the behaviour
after that, the experimenters see which stimuli will cause the animal to reinstate drug-seeking behaviour (engage in drug administering behaviour again) even though there is no drug available
things like stress, small dose of the drug, drug association cues are things that cause reinstatement
so this measures the likelihood of relapse of a drug after extinction
What is the conditioned place-preference experiment?
Involves a training chamber, where the rat is injected with a drug of unknown reinforcing properties and thenmoved into a neutral chamber
then from the neutral chamber, the rat decides if it wants to stay in the neutral chamber or go into the drug associated chamber that it was in before
if the rat chooses to go to the drug associated chamber, and spends more time there over the neutral chamber then theres higher reinforcing properties to the drug
if it spends more time in the neutral chamber then the drug was not as reinforcing
what do all strong reinforcers have in common?
they all stimulate dopamine release in certain regions of the brain
what is in-vivo microdialysis? what is it used for? what data does it obtain and how?
in-vivo microdialysis involves implanting a micro probe in the pleasure areas of the mice’s head sterotaxically (sterotaxic surgery).
once it is connected to the probe, the animal can move freely in a cage and the probe measures Neurotransmitter release changes when present with different stimuli
it does this by removing fluid in CSF from brain to measure and then pumping artificial CSF back into the brain of the mouse
this method allows experimenter to obtain levels of neurotransmitter from freely moving rats
what is a drawback of in-vivo microdialysis?
it has poor time resolution –> the sampling typically captures the release of dopamine over a few minutes rather than seconds so it misses some information
what does the in-vivo microdialysis dopamine measurements show in research?
the baseline dopamine is at 100%
the highest natural activity that causes high dopamine release is at 160%
for drugs of abuse it spikes up to 1100% (amphetamines) and 400% in cocaine
what is the best way to measure rapid dopamine release?
fast-scan cyclic voltammetry because it can get a resolution in an order of seconds than minutes but its an indirect way of measuring dopamine concentration
it works by measuring the oxidation of dopamine (loss of electrons) when a low voltage is applied to a probe
the results of it show that aversive stimuli like quinine can decrease basal release of dopamine and sucrose can increase the dopamine
what is the electrophysiological method of obtaining dopamine measurements?
rat wears apparatus that looks like a hat with two probes thats implanted.
shows real time actions of all neurons around the probe when drug is given
looks at the number of times neurons fire per second
it has the fastest time resolution
can measure electrical responses of individual neurons
what is the reward pathway called and what is a key NT that it relys on?
the reward pathway is called the mesocorticolimbic pathway and it relies on dopamine as the major NT
its called this pathway because most drugs indirectly or ddirectly stimulate the components of this pathway, disruption of this pathway prevents self administration (so does blocking dopamine receptors in this pathway), and block of dopamine receptors also produces anhedonia (loss of ability to feel pleasure) and motivation loss
where does the dopamine come from in the brain?
comes from dopamine-releasing neurons in the ventral tegmental area
this area is excited by drugs of abuse and causes it to release dopamine into the nucleus accumbens which is correlated to reward and feelings of euphoria
also releases to the amygdala and hippocampus –> associated with emotion (pleasure) and memory/learning
and the prefrontal cortex –> associated with higher cognitive function
what are the two components of the mesocorticolimbic pathway?
mesocortical (amygdala and hippocampus) and mesocortical (VTA + nucleus accumbens)
what is phasic and tonic release?
phasic release is when the VTA releases a bunch of dopamine to the NA and mesocortical pathway after a drug is taken
tonic release is the background release of dopamine at rest to these structures
which structures in the reward pathway release glutamate and which do not?
prefrontal cortex, amygdala, VTA, and hippocampus all release glutamate but the nucleus accumbens doesnt because its GABAergic
what are the medium spiny neurons (MSN’s) in nucleus accumbens? what are their properties? and what are the properties of d1 and d2 receptors?
this is located in the ventral portion of the striatum and 95% of neurons there are MSN’s
they release GABA when depolarized
they have two major divisions, those that have d1 receptors, and those that have d2 receptors
the d1 and d2 receptors have different output paths in the Nucleus accumbens
d1 receptors are associated with reward and d2 receptors are associated with aversion
activation of both receptors susually results in increased locomotion
they have dopamine (from VTA), glutamate (input from PFC mainly, but also from hippocampus and amygdala) and other NT’s modulating their activity
MSN’s gather info from other neurons because dnedritic spines on their dendrites allow it
VTA neuronal axon releases dopamine to nucleus accumbens and the dopamine binds on its corresponding d1 or d2 receptor in the nucleus accumbens
how do cues trigger memory-related structures in the reward pathway? what do cues do to the reward pathway?
cues trigger memory structures, and this can lead to reinstatement (relapse) of drug seeking behaviour)
the amygdala and hippocampus become active in the presence of drug associative cues and seems to be a major component of craving
their output influences other components in the reward pathway
extinguished drug taking behaviour in animals can be restarted by directly stimulating the hippocampus
What do acute drug effects do to the reward pathway?
- they are predominately dopamine-related
- theres an increase level of dopamine in the NA during drug taking and during anticipation of drug taking
- memory related structures are stimulated via dopamine creating a strong emotional memory of drug taking events and u get over learning of events related to drug taking which can be responsible for craving and relapse
what do chronic drug effects do to the reward pathway?
chronic effects involve glutamate and dopamine
- repeated drug use changes the strength of glutamate signalling between components of the pathways
- changes in PFC modulation by dopamine results in loss of both behavioural control and appropriate decision making by abnormal glutamate signalling from PFC
glutamate-mediated signaling from PFC, amygdala and hippocampus to NA is altered with chronic use
