Lecture 3: Addiction and the Brain

Question 1

what is thought to happen to the reward pathway when exposed to drugs of abuse?

Answer 1

reward pathway is there for survival increase to prompt an animal to repeat rewarded behaviours

this pathway gets hijacked by drugs of abuse

Question 2

what does the strength of reinforcing property correlate with?

Answer 2

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

Question 3

what is an example of an animal model of reinforcement?

Answer 3

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

Question 4

what are two schedules of drug administration used to give drugs to animal models?

Answer 4

1. 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
2. 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.

Question 5

what is extinction?

Answer 5

reducing the drug seeking behaviour to zero by removing the reward and drug in general

Question 6

What are some activities in humans that can affect self administration?

Answer 6

1. presence of an alternative stimuli like high quality food, exercise equipment
2. drug history
3. gender
4. environment (enriched enviroments can reduce risks of drug taking behaviour)

Question 7

what is the reinstatement paradigm? what does it measure?

Answer 7

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

Question 8

What is the conditioned place-preference experiment?

Answer 8

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

Question 9

what do all strong reinforcers have in common?

Answer 9

they all stimulate dopamine release in certain regions of the brain

Question 10

what is in-vivo microdialysis? what is it used for? what data does it obtain and how?

Answer 10

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

Question 11

what is a drawback of in-vivo microdialysis?

Answer 11

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

Question 12

what does the in-vivo microdialysis dopamine measurements show in research?

Answer 12

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

Question 13

what is the best way to measure rapid dopamine release?

Answer 13

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

Question 14

what is the electrophysiological method of obtaining dopamine measurements?

Answer 14

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

Question 15

what is the reward pathway called and what is a key NT that it relys on?

Answer 15

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

Question 16

where does the dopamine come from in the brain?

Answer 16

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

Question 17

what are the two components of the mesocorticolimbic pathway?

Answer 17

mesocortical (amygdala and hippocampus) and mesocortical (VTA + nucleus accumbens)

Question 18

what is phasic and tonic release?

Answer 18

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

Question 19

which structures in the reward pathway release glutamate and which do not?

Answer 19

prefrontal cortex, amygdala, VTA, and hippocampus all release glutamate but the nucleus accumbens doesnt because its GABAergic

Question 20

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?

Answer 20

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

Question 21

how do cues trigger memory-related structures in the reward pathway? what do cues do to the reward pathway?

Answer 21

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

Question 22

What do acute drug effects do to the reward pathway?

Answer 22

1. they are predominately dopamine-related
2. theres an increase level of dopamine in the NA during drug taking and during anticipation of drug taking
3. 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

Question 23

what do chronic drug effects do to the reward pathway?

Answer 23

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