lecture 9 LOs

Question 1

how are DA/NE removed from the synaptic cleft

Answer 1

membrane transporter proteins
commonly referred to as DAT and NET
sloppy
in the frontal lobes most DA reuptake is done by NET

Question 2

what does blocking transporters lead to

Answer 2

greater accumulation of extracellular NT levels

Question 3

what is release of reuptake blockers dependent on

Answer 3

activity of the neuron
if neurons are not firing then reuptake blockers will not increase transmitter levels

Question 4

what does cocaine inhibit the reuptake of

Answer 4

all monoamines (DA, NE, 5-HT)

Question 5

what does tricyclic antidepressant inhibit the reuptake of

Answer 5

NE and 5-HT

Question 6

what does methyphenidate (ritalin) selective for

Answer 6

catecholamines

Question 7

what does amephtamine do to the DA/NE transporter

Answer 7

reverse it so it spits out moleculesm from inside the terminal into the synapse
more transmitter is released and stays out a lot longer

Question 8

amphetamines are ____ of cell firing

Answer 8

independent
even if the neuron is not firing, amphetamines can still increase transmitter levels

Question 9

are amphetamines more selective or non selective

Answer 9

non selective, will work on DA, NE, and 5-HT

Question 10

what do amphetamines that enter the brain invariably do

Answer 10

increase locomotor activity
driven primarily by the increased DA in nuecleus accumbens

Question 11

what do high doses of amphetamines result in

Answer 11

stereotyped behaviours
snigging, repetitive head/limb movements, licking, biting)

Question 12

what does the continuum of beh changes from amphetamine doses come from

Answer 12

increase stimulation of DA receptors in the nucleus accumbens and striatum

Question 13

what is sensitization

Answer 13

repeated exposure increases sensitivity to effects of drug at the same dose

Question 14

therepeutic effects of small doses of d-amphetamine

Answer 14

powerful stimulat: promotes wakefulness, reduces REM sleep
cognitive enhancer: for multiple forms of cognition

Question 15

DA and NE receptor subtypes

Answer 15

DA autoreceptor: D2 subtype
NE autoreceptor: alpha 2 subtype

Question 16

where do monoamine autoreceptors reside

Answer 16

axon terminals (DA and NE)
cell bodies (NE)

Question 17

what does activation of DA and NE receptors result in

Answer 17

opening of voltage gated K+ channel that shortens duration of action potentials
on terminals this reduces Ca2+ influx and transmitter exocytosis

Question 18

what do autoreceptors on the cell body do

Answer 18

reduce neural firing

Question 19

where else can D2/alpha 2 receptors reside

Answer 19

postsynaptic neurons

Question 20

DA cell groups A1-7

Answer 20

nonadrenergic

Question 21

DA cell groups A8-16

Answer 21

dopaminergic

Question 22

where do A9 (nigrostriatal) axons originate from

Answer 22

substantia nigra and extend to caudate putamen (dorsal striatum)

Question 23

what does the nigrostriatal DA facilitate

Answer 23

voluntary movement
parkinsons involves these neurons
6-OHDA and MPTP are used to destroy these cells in this pathway in animal models for parkinsons

Question 24

what does dorsal striatum DA aide in

Answer 24

action selection, promotes the best action while expressing the others

Question 25

the A10 cell group in the VTA gives rise to two pathways

Answer 25

mesolimbic
mesocortical

Question 26

mesolimbic pathway extension

Answer 26

various limbic system nuclei
nucleus accumbens, amygdala
DA input to accumbens facilitates forward locomotion

Question 27

what is the mesolimbic pathway heavily linked to

Answer 27

reward and motivational functions

Question 28

mesocortical DA terminals

Answer 28

have few DA transporters, most DA clearance in the cortex is done by COMT and NET

Question 29

what do blockages of the mesocortical pathway link to

Answer 29

congnitive functions
blockade of PFC DA receptors impairs executive functions
DA D1receptors more heavily expressed in prefrontal regions (vs D2)

Question 30

PFC DA modulates ___ witin an optimum range

Answer 30

cognition

Question 31

dopamine receptor subtypes

Answer 31

D1 to D5
all are metabotropic, interact w G proteins and second messengers

Question 32

what does D1 activation stimulate

Answer 32

adenylyl cyclase and cAMP synthesis

Question 33

what does D2 activation do

Answer 33

reduces cAMP

Question 34

how do D2 receptors function

Answer 34

as both autoreceptors and postsynaptic receptors

Question 35

how do D2 antagonists increase DA release

Answer 35

by blocking the autoreceptor, but also reduce postsynaptic DA signalling

Question 36

does D2 or D1 have higher affinity for dopamine

Answer 36

D2

Question 37

some DA receptors are ___ for glutamate/GABA terminals and modulate…

Answer 37

heteroreceptors
fast transmission presynaptically

Question 38

dopamine agonist

Answer 38

apomorphine
stimulates D1 and D2 receptors
causes beh similar to what is seen w cocaine or amphetamines
DA receptor agonists are used for treatment of parkinsons

Question 39

dopamine antagonist

Answer 39

flupenthixol
blocks D1 and D2 receptors
reduces motivation and at higher doses produces catalepsy (lack of spontaneous movement) like all D1 or D2 antagonists

Question 40

haloperidol

Answer 40

highly selective for D2 vs D1 but will still bind to D2,3,4 w similar affinity