3-addiction and brain Flashcards
what is the concept/question of abuse potential
are some drugs more likely to result in addiction/dependence than others?
what do drugs of abuse do to the reward pathway (basic)
artificially manipulate/”hijack” the reward pathway
what is reinforcement
a behavioural event followed by a consequent event such that the behaviour is then more likely to be repeated
what is a fixed ratio schedule (in studying the strength of reinforcement properties of a drug)
animal is required to perform behaviour a specific number of times to achieve reward
what is a progressive ratio schedule (in studying the strength of reinforcement properties of a drug)
animal is required to perform an increasing number of responses for subsequent reward
what strongly correlates with abuse/addiction potential of drug
a high strength of reinforcing property
what is extinction
reduce the drug seeking behaviour ti zero by removing the reward/drug
what is a good way to test how far an animal is willing to go to get the drug? (2 main things)
start with fixed-ratio schedule then move to progressive ratio schedule (it may have to perform the same task hundreds of times)
what is the reinstatement paradigm
the measure of vulnerability to relapse into drug abuse
how do they do the reinstatement paradigm in experiments (4 steps)
- animals trained to self administer
- extinguish behaviour by discontinuing drug
- animal gives up on behaviour
- test different stimuli to see what will cause the animal to reinstate drug seeking behaviour (even tho no drugs there)
what are the main things that cause reinstatement in humans (3)
stress
small dose of drug
drug associated cues
what is conditioned place-preference experiment
-room with specific colours is where they administer drug. then later they see if the animal will go back to that one or a neutral room
what does it mean if the animal prefers the drug associated chamber
drug is probably reinforcing
what does it mean if the animal prefers the neutral chamber
drug probably has a negative effect
what does it mean if the animal doesnt prefer the neutral chamber or the drug associated chamber
the drug probably has no effect
what do all strong reinforcer drugs have in common
all stimulate dopamine release in certain regions of the brain
what is in vivo microdialysis
implant a probe (stereotaxic surgery) in specific brain region and collect fluid to analyze its neurotransmitter levels
what did microdialysis dopamine measurements tell us about natural vs drug induced dopamine release
a lot more dopamine is released via drugs rather than naturally stimulating things
what does a bigger dose of drugs do to the amount of DA released in the nucleus accumbens
increases DA release
what is fast-scan cyclic voltammetry and how does it work
captures rapid dopamine release (in concentrations) within seconds
measures the oxidation of dopamine (loss of e) when low voltage is applied to probe
what is a downside to in-vivo microdialysis
it is slow (minutes to get info) so you may miss important info and you have to pump fluid back into the brain
what does quinine do to dopamine release and why
it is an aversive stimuli, so it decreases basal release of dopamine
what is electrophysiology / how does it work
measures the activity of neurons that are releasing dopamine by implanting electrodes to measure the change in electrical properties of neurons
what 2 things makes electrophysiology great
fast
can measure electrical response of individual neurons
what are the 3 techniques for measuring dopamine in the brain
microdialysis
fast-scan cyclic voltammetry
electrophysiology
what is the technical name of the reward pathways (2 and the combined name)
mesolimbic
mesocortical
mesocorticolimbic
what is the major neurotransmitter of the mesocorticolimbic pathway
dopamine
why can you link the mesolimbic and mesocortical pathway into the mesocorticolimbic pathway
most drugs indirectly or directly stimulate components of these pathways
what happens to drug use if you disrupt the mesolimbic pathway
prevents self-administration (and blocks dopamine receptors)
also causes anhedonia (no more happy)
why cant you treat drug addicts by disrupting the mesolimbic pwahway
you get anhedonia (no more pleasure) and motivation loss
where is dopamine released
the ventral tegmental area VTA
where does dopamine from the ventral tegmental area release onto
nucleus accumbens
amygdala
hippocampus
prefrontal cortex
what happens with increased dopamine in the nucleus accumbens
reward and euphoria (pleasure centre)
what is the role of the amygdala and hippocampus
memory
what is the role of the prefrontal cortex
higher cognitive function
is dopamine excitatory or inhibitory
both, depending on what type of dopamine receptor it interacts with
is GABA excitatory or inhibitory
inhibitory
what does it mean for a neurotransmitter to be inhibitory
it decreases the probability of depolarization
is glutamate excitatory or inhibitory
some are excitatory
some presynaptic ones are inhibitory (negative feedback system for glutamate release)
what neurotransmitter is responsible for anticipating and receiving drugs, euphoria and behaviour reinforcement
Dopamine
what is phasic dopamine release
and the average #
burst of DA release in response to something
midbrain dopamine neurons firing at 20/sec
what is tonic dopamine release
and the average #
background/basal level of constant DA release
midbrain dopamine neurons firing at 1-5/sec
what centres are involved in the mesolimbic pathway
VTA sending out to the nucleus accumbens, the amygdala and the hippocampus
what kind of behaviours are associated to the limbic system
primitive emotional behaviours
what centres are involved in the mesocortical pathway
VTA to the prefrontal cortex
what parts of the brain respond to the dopamine message by sending out glutamate? And to where?
- PFC, VTA, amygdala, hippocampus and PFC to nucleus accumbens
- PFC to VTA
- amygdala to VTA
- hippocampus to PFC
what are 95% of the neurons in the nucleus accumbens
medium spiny neurons (MSNs)
where are the medium spiny neurons
ventral portion of the nucleus accumbens
what do medium spiny neurons release when depolarized
GABA
what are the 2 major divisions of medium spiny neurons?
where are they found?
ones with D1 and D2 receptors
on two different output paths from the nucleus accumbens
what is the difference with D1 and D2 receptors
D1=excitatory
D2=inhibitory
what does activation of D1 and D2 do
it usually results in increased locomotion (Even though they are 50/50, they still overall cause excitation)
what are the cortical and dopamine afferents from that connect to the medium spiny neurons
cortical afferents from prefrontal cortex
dopamine afferents from the VTA
what modulates the activity of medium spiny neurons
dopamine, glutamate and other neurotransmitters
what part of the brain become most activated in the presence of drug associated cues
amygdala and hippocampus
what parts of the brain seem to be a major component of craving
amygdala and hippocampus due to memories of drug - fires up the whole reward pathway
how can you reinstate drug-taking behaviour in animals even after extinction
by stimulating the hippocampus
what neurotransmitter(s) are involved with acute drug effects
dopamine
what neurotransmitter(s) are involved with chronic drug effects
glutamate and dopamine
what happens with acute drug taking to the nucleus accumbens
flooded with dopamine, gives euphoria and reinforces drug taking behaviour
what happens with acute drug taking to the hippocampus and amygdala
memory centres create a strong emotional memory(overlearning), may be responsible for craving and relapse
what is overlearning
learning abnormality caused by drugs-so much dopamine that these memories are deeply engrained and have priority over other important memories - minor cues can trigger these major drug memories
what does chronic drug use do to glutamate signalling
changes the strength of glu signalling between pathways,
how is the PFC effected from chronic drug use (neurotransmitters)
abnormal glutamate and dopamine signalling causes a loss of behavioural control and decision making
in what way has glutamate signalling become altered (where)
signalling from PFC, amygdala and hippocampus to the nucleus accumbens
