Carboni, … DiChiara et al. J Neurosci 20:RC102(1-5), 2000 What do we know about addictive drugs from animal studies? “… cocaine, morphine, nicotine, and ethanol share the property of increasing DA transmission in the BNST. This effect may be related to an action at the level of neuronal circuits activated by natural reinforcers … suggest[ing] that DA transmission of the BNST plays a role in the mechanism of drug abuse and addiction.”

aaarrrggghhhh!!!!! – show me  BP

what phenomenon is this?

does everyone understand what they are showing here? euphoria  BP Individual subjects (need to have all brains in same space) plot R value at given voxel

de-nic cignic cig

muD2

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects10 smokers 20 smokers (control, smoking) 6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typehigh/low nicown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typeown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typeown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott tracer11C-raclopride 11C-raclopride (and carfentanil) injection protocolBolus + infusionBolus (x2)bolus + infusion tracer dose?10 mCi10-15 mCi Kbol (ml/[ml/min])100 mininfinite 90? (half and half in 90 min study) scanner (resolution)ECAT 953 (5.6 mm FWHM)HR+ (4.2 mm FWHM)HR+ (5.5 mm?) designinter-subject (1 scan)intra-subject (s scan) intra-subject (1 scan – 2 different cigs) phenomenon to testsmoking nicotine (only) subjects 20 smokers (10 smoking 10 control) 10 smokers6 smokers (m) smoking characteristics>15 cigs/day>18 cigs/day16.7 time from last cig 2 hrs (in w/d from caffeine, alcohol)) 12 hrsovernight protocol smoke 1 cigarette OUTSIDE scanner smoke 3-6 cigarettes INSIDE scanner in scanner nic--- and denic (control) cigs t=50min – 60 min smoke every 12 min -15 mn (denic) and (nic) self-adminyes forced smoking (some aversion) yes cigarette typeown brand high nic / low nic (research) finding in Ventr Str  BP corr w/ craving (reduction? all +) none yes “ventr basal ganglia” corr with dependence score finding in Dorsal Strnone?  BP related to pleasure (+,-) no

BrodyBarrettScott limitations movement low n low resolution scanner forced smoking aversion to cigs low n forced smoking? not regular brand very low n. model srtm ? don’t believe it (it was an infusion, I think they just used target/ref – 1) srtm Logan plot (use Logan slope from 5-40 and 45-90) (can’t find publication validating this approach) other calculations correlation images (understand what they did?) questions reward-prediction error? some foiund cigs aversive – DA went down – tha towuld hurt the differece reward-prediction error? got de-nic cig first, if DA went down that would help the difference order effects?yesnoyes best quote

No CS CS unexpected reward predicted reward absence of predicted reward from: Schultz, Dayan, & Montague, 1997, Science.

mu