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

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concepts to review

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  1. concepts to review mesolimbic Dopamine system microdialysis SRTM (ref reg models) BP images PET BP images SPM (voxel-wise t-tests)

  2. meoslimbic dopamine system

  3. infusate of aCSF and drug intracranial m-dialysis probe lines to sample collector

  4. 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

  5. n = 6 males

  6. no trick subjects apprised of drink type just before scan is this different from Urban? Is it different from Yoder?

  7. how consistent is the “typical alcohol curve?” what can be done to control it?

  8. 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.

  9. 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).

  10. compare to Urban who got 12% change in BP in VS in 11 males.

  11. n = 11 males; 10 females, analyzed separately

  12. 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?

  13. DA release related to frequency of max-drinking day? what does this mean? do men differ from women because they are demographically different?

  14. blinded? expectations? order effects? (need sham scan)

  15. n = 8 males cue (visual and OLFACTORY)

  16. olfactometer olfactory cues Mirror Goggles visual cues (EtOH/neutral) Experimental Setup IV EtOH Clamp PET Gantry

  17. Olfactometer (aka. the “smell-a-tron”) Delivery of odors to subject is computer controlled and synchronized with presentation of visual cues.

  18. IV Alcohol Infusion Mirror goggle Odors Computer-controlled EtOH infusion PET scanner

  19. Arterial Sampling (sometimes) Mirror Goggles Odors Arterial Cannula PET scanner

  20. bolus study order effects? why? can it be avoided? not self admin is iv alcohol like drinking? look at behavioral self reports

  21. 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).

  22. 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.”

  23. 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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