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.
mesolimbic Dopamine system
SRTM (ref reg models)
PET BP images
SPM (voxel-wise t-tests)
intracranial m-dialysis probe
lines to sample collector
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
subjects apprised of drink type just before scan
is this different from Urban?
Is it different from Yoder?
what can be done to control it?
The picture (DBP) is “weighted” by the scenes when the shutter is open widest.
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).
n = 11 males; 10 females, PET?analyzed separately
design issues: PET?
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?
DA release related to frequency of max-drinking day? what does this mean?
do men differ from women because they are demographically different?
blinded? does this mean?
(need sham scan)
n = 8 males does this mean?
cue (visual and OLFACTORY)
olfactometer does this mean?
visual cues (EtOH/neutral)Experimental Setup
IV EtOH Clamp
Delivery of odors to subject is computer controlled and synchronized with presentation of visual cues.
Computer-controlled EtOH infusion
bolus study does this mean?
order effects? why? can it be avoided?
not self admin
is iv alcohol like drinking? look at behavioral self reports
No does this mean? CS
from: Schultz, Dayan, & Montague, 1997, Science.
predicted rewardConclusions- I
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 DBP
(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.”
Yoder: SHAS and AUDIT scores NOT correlated with experiment in monkeys? Don’t we need prior conditioning? What is the author’s answer to this?**DBP
Boileau: SHAS scores did not correlate with DBP
impulsiveness predicted BP change in VS