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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). meoslimbic dopamine system. infusate of aCSF and drug. intracranial m -dialysis probe. lines to sample collector.

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concepts to review

concepts to review

mesolimbic Dopamine system

microdialysis

SRTM (ref reg models)

BP images

PET BP images

SPM (voxel-wise t-tests)

slide3

infusate of aCSF and drug

intracranial m-dialysis probe

lines to sample collector

consider the effect of nicotine on dopamine
Consider the effect of nicotine on dopamine

Dopamine Concentration

SD rats

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

slide6

no trick

subjects apprised of drink type just before scan

is this different from Urban?

Is it different from Yoder?

the free tracer is the shutter of the dopamine camera
The free tracer is the “shutter”of the “dopamine-camera”

DA

time

Free

11C-raclopride

FRAC(t)

Free

dopamine

DA(t)

The picture (DBP) is “weighted” by the scenes when the shutter is open widest.

but what does that mean for detecting da release with pet
But – what does that mean for detecting DA release with PET?

DA

time

The pattern of shutter “opening” and “closing” is a function of the tracer parameters (K1, k2, kon, koff, etc)

Free

dopamine

DA(t)

Free

tracer

FRAC(t)

This has consequences for experimental design (including choice of tracer).

slide12

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?

slide13

DA release related to frequency of max-drinking day? what does this mean?

do men differ from women because they are demographically different?

slide15

blinded?

expectations?

order effects?

(need sham scan)

slide16

n = 8 males

cue (visual and OLFACTORY)

experimental setup

olfactometer

olfactory cues

Mirror

Goggles

visual cues (EtOH/neutral)

Experimental Setup

IV EtOH Clamp

PET Gantry

olfactometer aka the smell a tron
Olfactometer (aka. the “smell-a-tron”)

Delivery of odors to subject is computer controlled and synchronized with presentation of visual cues.

iv alcohol infusion
IV Alcohol Infusion

Mirror goggle

Odors

Computer-controlled EtOH infusion

PET scanner

arterial sampling
Arterial Sampling

(sometimes)

Mirror

Goggles

Odors

Arterial Cannula

PET scanner

slide21

bolus study

order effects? why? can it be avoided?

not self admin

is iv alcohol like drinking? look at behavioral self reports

conclusions i

No CS

unexpected

reward

from: Schultz, Dayan, & Montague, 1997, Science.

CS

predicted

reward

CS

absence of

predicted reward

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).
slide24

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.”

slide25

Yoder: SHAS and AUDIT scores NOT correlated with DBP

Boileau: SHAS scores did not correlate with DBP

impulsiveness predicted BP change in VS

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