CNS Disorders Flashcards
what are the different methods of studying CNS disorders
imaging
post-mortem
indirect neuropharmacological markers
genetics-linkage analysis
animal models
what are the different imaging techniques for studying CNS disorders
computerized tomography - CT
Magnetic resonance imaging - MRI
functional MRI - fMRI
what is the spatial resolution of a CT scan
several mm
what is MRI technology based on an its spatial resolution
oxyhaemoglobin has a different magnetic resonance than deoxyhaemoglobin
less than 1mm
what is the basis of how fMRI’s work
visual stimulation utilises oxygen
microvasculature responds by increasing blood flows to specific brain regions
leads to increase in the oxyHb to deoxyHb ratio
function of diffusion tensor imaging
mapping pathways and investigating aberrant pathways
what is the difference between a PET and a SPET scan and what is the advantage and what do they both do
SPET uses single positron emissions and doesn’t need a cyclotron
reveal activity in the brain and estimate receptor levels
what are other non-invasive imaging techniques
electroencephalography
magnetoencephalography
when detecting for indirect markers where would you search
cerebrospinal fluid
plasma
urine
binding to platelets
what is an indirect marker for depression
platelet binding - binding to monoamine transporter
what are the disadvantages of using indirect markers for CNS disorders
proteins are labile - may degrade
patient may be taking medication
what does genetic-linkage analysis detect
RFLPs - restriction-fragment length polymorphisms
what does RFLPs require and what is its purpose in genetic-linkage analysis
requires family pedigree of the genetic disease
easiest to study in genetically isolated communities
detects whether the RFLPs and the disease are linked
why might genetic-linkage analysis using RFLPs not be effective with some diseases
may involve multiple genes
or involve mitochondrial DNA
what are the dis/advantages of using animal models
advantage - drug screening for therapies
disadvantage - not an exact phenocopy of the disease
where is ayahuasca derived from and what is the active psychomimetic ingredient
obtained from vines
harmaline
what is the active constituent in peyote
mescaline
why might lysergic acid diethylamide (LSD) be so potent
act very specifically at receptors sites in the brain
what does the cross-tolerance between LSD and mescaline suggest
they both act on the same class of receptor site
what is the structure of LSD and mescaline similar to
5-HT - seretonin
what does LSD act as in terms of 5-HT receptors
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
what does the effects of LSD suggest it alters
primary somatosensory cortex
thalamus
what is the function of raphe neurones and how does LSD effect them
send extensive projections to the forebrain
decreases their firing rate
what did lesioning the raphe nucleus in rats tell us about the effects of decreased firing rate of raphe neurones via LSD
that they did not exert the hallucinogenic effects
rats were able to distinguish saline from LSD
what does LSD increase activity in
locus coeruleus neurones
also increases activity in subsets of neurones in the cortex
where are 5HT2A receptors present
temporal cortex
prefrontal cortex
thalamus
function of the thalamus
processes somatosensory information and receives information from the locus coeruleus
if 5HT2A receptors mediate hallucinogenic action then what is the rationale behind testing for different hallucinogen potency
that drugs with higher 5HT2A affinity will produce more potent hallucinogenic effects and vice versa
where 5HT2A receptors expressed
pyramidal neurones in the cortex
how does LSD effect the cortex
increases activity of layer V pyramidal neurones in the cortex
what do imaging studies of LSD suggest
higher cortical activity
what is phencyclidine (PCP)
a dissociative anaesthetic
same class as ketamine
what does phencyclidine induce
causes a catatonic like state without muscle relaxation
what do radioligand studies of PCP show it interacts with
sigma opiate receptors - modulates NAdr release
non-competitive antagonist of glutamate receptors (NMDA)
what are the features of addiction
compulsion to take drug
tolerance to drug
withdrawal symptoms - opposite effects to those in presence of drug
what is an operant chamber
an environment that allows a rat to self administer a drug
what is the evidence that suggests that dopamine pathways are important for reinforcing
administration of spiroperidol - a DA antagonist and 6A-OH-DA lesions both block reinforcement
where do Da/NAdr/5-HT pathways originate from and what are they implicated in
midbrain/medulla - medial forebrain bundle
mood/behaviour
where do dopamine axons project from and too
the medial forebrain bundle
nucleus accumbens
what is the evidence for specific transporters in the reinforcing properties of cocaine
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
what is the function of F105
important for high affinity binding of cocaine but not for DA transport
what was the effect of cocaine in mice with knock-in mutant dopamine transporter
did not elevate extracellular dopamine or increase locomotion
affect of ethanol on dopamine release
increases DA release in the nucleus accumbens
effect of dopamine transporter antagonist in animal models
blocks ethanol self-administration
effect of opiates on the limbic system
increases dopaminergic activity
function of fluoromethylspiroperidol
used to label dopamine receptors in PET scans
in terms of genes what is the long-term effect of addiction
increase in DA leads to increase in cAMP leads to activation of CREB which leads to immediate early gene expression
what may the addiction induced immediate early gene expression cause
changes in receptor levels
what was found in rat models to be associated with high alcohol preference
innate/acquired hyperactivity of extrahypothalamic CRF systems
