CNS Disorders

Question 1

what are the different methods of studying CNS disorders

Answer 1

imaging
post-mortem
indirect neuropharmacological markers
genetics-linkage analysis
animal models

Question 2

what are the different imaging techniques for studying CNS disorders

Answer 2

computerized tomography - CT
Magnetic resonance imaging - MRI
functional MRI - fMRI

Question 3

what is the spatial resolution of a CT scan

Answer 3

several mm

Question 4

what is MRI technology based on an its spatial resolution

Answer 4

oxyhaemoglobin has a different magnetic resonance than deoxyhaemoglobin
less than 1mm

Question 5

what is the basis of how fMRI’s work

Answer 5

visual stimulation utilises oxygen
microvasculature responds by increasing blood flows to specific brain regions
leads to increase in the oxyHb to deoxyHb ratio

Question 6

function of diffusion tensor imaging

Answer 6

mapping pathways and investigating aberrant pathways

Question 7

what is the difference between a PET and a SPET scan and what is the advantage and what do they both do

Answer 7

SPET uses single positron emissions and doesn’t need a cyclotron
reveal activity in the brain and estimate receptor levels

Question 8

what are other non-invasive imaging techniques

Answer 8

electroencephalography
magnetoencephalography

Question 9

when detecting for indirect markers where would you search

Answer 9

cerebrospinal fluid
plasma
urine
binding to platelets

Question 10

what is an indirect marker for depression

Answer 10

platelet binding - binding to monoamine transporter

Question 11

what are the disadvantages of using indirect markers for CNS disorders

Answer 11

proteins are labile - may degrade
patient may be taking medication

Question 12

what does genetic-linkage analysis detect

Answer 12

RFLPs - restriction-fragment length polymorphisms

Question 13

what does RFLPs require and what is its purpose in genetic-linkage analysis

Answer 13

requires family pedigree of the genetic disease
easiest to study in genetically isolated communities
detects whether the RFLPs and the disease are linked

Question 14

why might genetic-linkage analysis using RFLPs not be effective with some diseases

Answer 14

may involve multiple genes
or involve mitochondrial DNA

Question 15

what are the dis/advantages of using animal models

Answer 15

advantage - drug screening for therapies
disadvantage - not an exact phenocopy of the disease

Question 16

where is ayahuasca derived from and what is the active psychomimetic ingredient

Answer 16

obtained from vines
harmaline

Question 17

what is the active constituent in peyote

Answer 17

mescaline

Question 18

why might lysergic acid diethylamide (LSD) be so potent

Answer 18

act very specifically at receptors sites in the brain

Question 19

what does the cross-tolerance between LSD and mescaline suggest

Answer 19

they both act on the same class of receptor site

Question 20

what is the structure of LSD and mescaline similar to

Answer 20

5-HT - seretonin

Question 21

what does LSD act as in terms of 5-HT receptors

Answer 21

interacts with 5-HT receptors in peripheral vasculature
in the periphery it acts as a 5-HT2 receptor antagonist
in the brain it acts a 5-HT receptor agonist/partial agonist

Question 22

what does the effects of LSD suggest it alters

Answer 22

primary somatosensory cortex
thalamus

Question 23

what is the function of raphe neurones and how does LSD effect them

Answer 23

send extensive projections to the forebrain
decreases their firing rate

Question 24

what did lesioning the raphe nucleus in rats tell us about the effects of decreased firing rate of raphe neurones via LSD

Answer 24

that they did not exert the hallucinogenic effects
rats were able to distinguish saline from LSD

Question 25

what does LSD increase activity in

Answer 25

locus coeruleus neurones also increases activity in subsets of neurones in the cortex

Question 26

where are 5HT2A receptors present

Answer 26

temporal cortex prefrontal cortex thalamus

Question 27

function of the thalamus

Answer 27

processes somatosensory information and receives information from the locus coeruleus

Question 28

if 5HT2A receptors mediate hallucinogenic action then what is the rationale behind testing for different hallucinogen potency

Answer 28

that drugs with higher 5HT2A affinity will produce more potent hallucinogenic effects and vice versa

Question 29

where 5HT2A receptors expressed

Answer 29

pyramidal neurones in the cortex

Question 30

how does LSD effect the cortex

Answer 30

increases activity of layer V pyramidal neurones in the cortex

Question 31

what do imaging studies of LSD suggest

Answer 31

higher cortical activity

Question 32

what is phencyclidine (PCP)

Answer 32

a dissociative anaesthetic same class as ketamine

Question 33

what does phencyclidine induce

Answer 33

causes a catatonic like state without muscle relaxation

Question 34

what do radioligand studies of PCP show it interacts with

Answer 34

sigma opiate receptors - modulates NAdr release non-competitive antagonist of glutamate receptors (NMDA)

Question 35

what are the features of addiction

Answer 35

compulsion to take drug tolerance to drug withdrawal symptoms - opposite effects to those in presence of drug

Question 36

what is an operant chamber

Answer 36

an environment that allows a rat to self administer a drug

Question 37

what is the evidence that suggests that dopamine pathways are important for reinforcing

Answer 37

administration of spiroperidol - a DA antagonist and 6A-OH-DA lesions both block reinforcement

Question 38

where do Da/NAdr/5-HT pathways originate from and what are they implicated in

Answer 38

midbrain/medulla - medial forebrain bundle mood/behaviour

Question 39

where do dopamine axons project from and too

Answer 39

the medial forebrain bundle nucleus accumbens

Question 40

what is the evidence for specific transporters in the reinforcing properties of cocaine

Answer 40

Mice with DA transporter knockout have chronically elevated synaptic dopamine cocaine administered to these animals produces no change in base-line DA these animals will still administer cocaine there may be another reinforcing stimulus other than DA

Question 41

what is the function of F105

Answer 41

important for high affinity binding of cocaine but not for DA transport

Question 42

what was the effect of cocaine in mice with knock-in mutant dopamine transporter

Answer 42

did not elevate extracellular dopamine or increase locomotion

Question 43

affect of ethanol on dopamine release

Answer 43

increases DA release in the nucleus accumbens

Question 44

effect of dopamine transporter antagonist in animal models

Answer 44

blocks ethanol self-administration

Question 45

effect of opiates on the limbic system

Answer 45

increases dopaminergic activity

Question 46

function of fluoromethylspiroperidol

Answer 46

used to label dopamine receptors in PET scans

Question 47

in terms of genes what is the long-term effect of addiction

Answer 47

increase in DA leads to increase in cAMP leads to activation of CREB which leads to immediate early gene expression

Question 48

what may the addiction induced immediate early gene expression cause

Answer 48

changes in receptor levels

Question 49

what was found in rat models to be associated with high alcohol preference

Answer 49

innate/acquired hyperactivity of extrahypothalamic CRF systems