concepts to review
DESCRIPTION
concepts to review. mesolimbic Dopamine system microdialysis SRTM (ref reg models) BP images PET BP images SPM (voxel-wise t-tests). meoslimbic dopamine system. infusate of aCSF and drug. intracranial m -dialysis probe. lines to sample collector. - PowerPoint PPT PresentationTRANSCRIPT
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concepts to review
mesolimbic Dopamine system
microdialysis
SRTM (ref reg models)
BP images
PET BP images
SPM (voxel-wise t-tests)
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meoslimbic dopamine system
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3 lines to sample collector
intracranial -dialysis probe
infusate of aCSF and drug
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Consider the effect of nicotine on dopamine
DA responses in nucleus accumbens of SD rats measured by microdialysis. Time course for effects of 0.32 mg/kg SC nicotine (open circles);
Figure is from Coe et al., J Med Chem. May 19 2005;48(10):3474-3477
SD rats
Dop
amin
e C
once
ntra
tion
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n = 6 males
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no trick
subjects apprised of drink type just before scan
is this different from Urban?
Is it different from Yoder?
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how consistent is the “typical alcohol curve?”
what can be done to control it?
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0
d0
dt
K
)t(DA1
k
'Bk
dt)t(F
)t(F
BP
11
BP1
BPV
DA
off
maxon
RAC
RAC
11
1
The free tracer is the “shutter”of the “dopamine-camera”
Free
11C-raclopride
FRAC(t)
The picture (BP) is “weighted” by the scenes when the shutter is open widest.
DA
time
Free
dopamine
DA(t)
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But – what does that mean for detecting DA release with PET?
Free
tracer
FRAC(t)
DA
time
Free
dopamine
DA(t)
The pattern of shutter “opening” and “closing” is a function of the tracer parameters (K1, k2, kon, koff, etc)
This has consequences for experimental design (including choice of tracer).
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compare to Urban who got 12% change in BP in VS in 11 males.
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n = 11 males; 10 females, analyzed separately
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design issues:
no baseline – what happens if DA goes DOWN with placebo – is this still a valid comparison? a valid interpretation?
how do we know they got to steady state? is that necessary for their analysis?
why might DA go down with ‘placebo’
drink is 3 drinks-worth; forced drinking in 5-10 minutes? aversive?
differences are masked by vodka smell – will this induce negative reward-prediction error?
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DA release related to frequency of max-drinking day? what does this mean?
do men differ from women because they are demographically different?
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blinded?
expectations?
order effects?
(need sham scan)
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cue (visual and OLFACTORY)
n = 8 males
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Experimental Setup
IV EtOH Clamp
visual cues (EtOH/neutral)
olfactometer
MirrorGoggles
olfactory cues
PET Gantry
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Olfactometer (aka. the “smell-a-tron”)
Delivery of odors to subject is computer controlled and synchronized with presentation of visual cues.
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Mirror goggle
PET scanner
Odors
Computer-controlled EtOH infusion
IV Alcohol Infusion
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Arterial Cannula
Arterial Sampling (sometimes)
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bolus study
order effects? why? can it be avoided?
not self admin
is iv alcohol like drinking? look at behavioral self reports
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Conclusions- I• Data conform to
observations of dopaminergic function in reward prediction.
• Dopamine’s coding of expectation may be relevant to alcoholism (see Lapish, Seaman, & Chandler, 2006. ACER).
No CS
CS
CS
unexpectedreward
predictedreward
absence of predicted reward
from
: S
chul
tz,
Day
an,
& M
onta
gue,
199
7,
Sci
ence
.
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is the Yoder design really analogous to the Schulz experiment in monkeys? Don’t we need prior conditioning? What is the author’s answer to this?**
would like to know if anyone’s BP went wrong way (DA down) in Urban study – if so, it would agree with Yoder.
BAC in Boileau study did not correlate with BP
(agrees with Urban -- claimed it didn’t correlate with)
**Yoder et al: probably claim that prioir drinking exposure IS conditioning. So when they see and hear alcohol cues – they expect to get reward.
Consider figure 3. Subjects said: “It was clear I was about to get drunk.”
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Yoder: SHAS and AUDIT scores NOT correlated with BP
Boileau: SHAS scores did not correlate with BP
impulsiveness predicted BP change in VS