4-DA and glu

Question 1

when given Ritalin, did people with lots of D2 receptors or little D2 receptors react pleasantly to the experience?

Answer 1

low levels of D2 causes euphoria

Question 2

when given Ritalin, did people with lots of D2 receptors or little D2 receptors react negatively to the experience?

Answer 2

high levels of D2 causes dysphoria

Question 3

what levels of D2 receptors may be protective against addiction?

Answer 3

high levels

Question 4

how can you naturally increase D2 receptor levels?

Answer 4

exercise

Question 5

what does social stress do to D2 receptor levels?

Answer 5

decrease

Question 6

where are D2 receptors most affected in the brain?

Answer 6

nucleus accumbens (that is where you feel pleasure due to dopamine)

Question 7

what G protein do D1 receptors use?

Answer 7

Gs

Question 8

what G protein do D2 receptors use?

Answer 8

Gi/Go

Question 9

what are the 3 steps in Gs pathway?

Answer 9

adenylyl cyclase stimulated, increases cAMP levels, activates kinases to phosphorylate

Question 10

what are the 3 steps in Gi pathway?

Answer 10

inhibit adenylyl cyclase, inhibit Ca+ channels, activates potassium channels

Question 11

what does the activation of potassium channels do to neuronal firing (Gi)?

Answer 11

decreases probability that neuron will fire

Question 12

where are D1 receptors

Answer 12

on postsynaptic receptors

Question 13

where are D2 receptors

Answer 13

on presynaptic and postsynaptic receptors

Question 14

what does D1 receptors do to neurotransmission(excitatory or inhibitory)?

Answer 14

excitatory

Question 15

what does D2 receptors do to neurotransmission(excitatory or inhibitory)?

Answer 15

inhibitory

Question 16

what kind of pathways are associated to D1 type receptors

Answer 16

reward

Question 17

what kind of pathways are associated to D2 type receptors

Answer 17

aversion

Question 18

what is D1 affinity to dopamine and at what concentrations

Answer 18

low affinity (only active at high concentrations)

Question 19

what is D2 affinity to dopamine and at what concentrations

Answer 19

high affinity (1000X higher, active at much lower dopamine concentrations)

Question 20

love who?

Answer 20

FROG

Question 21

which dopamine receptors respond to tonic levels of dopamine

Answer 21

D2 (D1 cant, it needs high concentrations)

Question 22

which dopamine receptors respond to high levels of dopamine (bursts)

Answer 22

D1`

Question 23

if D1 and D2 receptors have different effects, why doesn’t dopamine cancel itself out when it activates the receptors?

Answer 23

they are found on different neuronal populations that form different pathways (reward vs. punishment)

Question 24

what 3 things happen once D2 receptors are activated

Answer 24

1-increase K+ channel and decrease Ca++ channel (hyperpolarization)
2-increase DAT
3-inhibits TH enzyme

Question 25

what is TH enzyme and what does it do

Answer 25

tyrosine hydroxylase which helps synthesis DA

Question 26

what is DAT

Answer 26

dopamine transporter (brings it inside the presynaptic neuron from the cleft

Question 27

why does D2 decrease Ca++ channel

Answer 27

because you need Ca++ to release NT from vesicles | AND it helps make the neuron more negative (hyperpolarized)

Question 28

why does low D2 cause a predisposition to likelyhood of addiction

Answer 28

because D2 are autoreceptors that help inhibit further dopamine release

Question 29

what happens when you knock out D2 receptors in mice and then give them cocaine

Answer 29

they become more sensitive to cocaine

Question 30

which type of neurons are D2 receptors on

Answer 30

the majority aren’t on DA releasing neurons

Question 31

how can D2 receptors affect glutamate release

Answer 31

because there are D2 receptors on glutamate releasing neurons, so if there is DA released and leaks out near another D2 receptor, it can inhibit glutamate release

Question 32

how can communication between diff. parts of the brain via glu or GABA be affected by DA? (ex:PFC communicating with amygdala)

Answer 32

DA influences the DA or GABA releasing neurons if they have D2 receptors on it, so it influences the excitability of the striatum

Question 33

how is dopamine release and expectation related

Answer 33

they are related because expectation drives the response-dopamine release can change (even with the same dose) depending on the expectations

Question 34

how would DA be released if the animal was given a dose smaller than expected

Answer 34

small - they ANGY (shuts down activity of neuron)

Question 35

how would DA be released if the animal was given a dose larger than expected

Answer 35

big - they HAPI

Question 36

what did the picture and dose experiment teach us about DA

Answer 36

not only reward, but also works with anticipation (and comparison of reward received to what was expected)

Question 37

what is the dopamine signalling in pre-reward caused by

Answer 37

due to learned behaviour from cues and expectations (like a pic associated to a dose)

Question 38

what is the dopamine signalling in post-reward caused by

Answer 38

summation of pharmacological properties of drug and expectation

Question 39

what is the role of glutamate in the brain (associated to how drugs affect the brain)

Answer 39

neuroplasticity, over-learning of behaviours and relapse

Question 40

what does glutamate signalling do to drug-related behaviours

Answer 40

it may "lock in" some of the behaviours

Question 41

where are 2 locations that glutamate is released

Answer 41

presynaptic terminals and glial cells

Question 42

where does/what causes the phasic/acute level of glutamate release

Answer 42

presynaptic terminals

Question 43

where does/what causes the tonic/basal level of glutamate release

Answer 43

glial cells

Question 44

what are mGluR (simple definition)

Answer 44

presynaptic metabotropic glutamate receptors

Question 45

what activates mGluR

Answer 45

glutamate release from glial cells

Question 46

what is the role of mGluR cells

Answer 46

to control sympathetic glutamate release (make sure there isnt excess release)

Question 47

what does the cystine-glutamate exchanger do

Answer 47

releases (approx. 60%) glutamate from the glial cells

Question 48

What does chronic drug use do to TONIC glutamate release

Answer 48

reduce it

Question 49

how does chronic drug use reduce the level of tonic glutamate release

Answer 49

inhibits the cystine-glutamate exchanger (decreases activation of presynaptic glutamate autoreceptors)

Question 50

why is more glutamate released during stress/ cue/drug stuff?

Answer 50

because cystine-glutamate exchanger is inhibited, which decreases activation of presynaptic glu autoreceptors, which turns off negative feedbacl

Question 51

what does excess glu do to the brain (2)

Answer 51

induces neuroplasticity and impairs communication between the PFC and nucleus accumbens

Question 52

what happens when both dopamine and glutamate are released on neurons in the nucleus accumbens

Answer 52

(ERK!) change in gene expression causing structure and function of neurons to change

Question 53

what is ERK stand for

Answer 53

extracellular signal-related kinase

Question 54

what causes the activation of ERK

Answer 54

only activated when dopamine and glutamate are released simultaneously on a signal neuron

Question 55

what does activation of ERK cause

Answer 55

changes in neuronal structure and proliferation | -long term changes

Question 56

where does ERK activation happen

Answer 56

postsynaptic side of a neuron, like the spiny neuron that receives both DA and glu input

Question 57

what are the steps in the ERK pathway(4)

Answer 57

- D1 activation leads to stimulation of glu receptor - D1 causes adenylyl cyclase and cAMP (Gs) - glu causes increase Ca2+ - ERK gets phosphorylated and can cause gene transcription (only happens if BOTH DA and glu pathways are activated)

Question 58

can ERK happen if D1 is activated but not NMDA

Answer 58

no

Question 59

is ERK activation increased or decreased with most drugs of abuse

Answer 59

increased

Question 60

what is a key role of ERK when it comes to drug abuse

Answer 60

neuronal plasticity

Question 61

what NT plays a role in transient neuroplasticity

Answer 61

dopamine

Question 62

what NT plays a role in stable neuroplasticity

Answer 62

glutamate and dopamine

Question 63

what is stable neuroplasticity

Answer 63

when your brain has already changed-it is very hard to turn back the effects of drugs

Question 64

how can you turn around compulsive relapse

Answer 64

behavioural intervention and pharmacology | -abstinence may not be enough