carboni, … dichiara et al. j neurosci 20:rc102(1-5), 2000 what do we know about addictive drugs...

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?

No CS

CS

CS

unexpectedreward

predictedreward

absence of predicted reward

from

: S

chul

tz,

Day

an,

& M

onta

gue,

199

7,

Sci

ence

.

does everyone understand what they are showing here?

40 50-12 -2

de-nic cig nic cig

mu

mu D2

Brody Barrett Scott

tracer 11C-raclopride 11C-raclopride 11C-raclopride (and carfentanil)

injection protocol Bolus + infusion Bolus (x2) bolus + infusion

tracer dose ? 10 mCi 10-15 mCi

Kbol (ml/[ml/min]) 100 min infinite 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?)

design inter-subject (1 scan) intra-subject (s scan) intra-subject (1 scan – 2 different cigs)

phenomenon to test smoking smoking nicotine (only)

subjects 10 smokers 20 smokers(control, smoking)

6 smokers (m)

smoking characteristics >15 cigs/day >18 cigs/day 16.7

time from last cig 2 hrs (in w/d from caffeine, alcohol))

12 hrs overnight

protocol smoke 1 cigarette OUTSIDE scanner

smoke 3-6 cigarettes INSIDE scanner

in scanner nic--- and denic (control) cigs

timing smoke-break @ t=50min – 60 min

smoke every 12 min start@ -15 mn

-12-8 (denic) and 40-60 (nic)

self-admin yes forced smoking(some aversion)

yes

cigarette type high/low nic own 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 Str none? BP related to pleasure (+,-) no

Brody Barrett Scott

limitations •movement•low n•low resolution scanner

•forced smoking•aversion to cigs•low n

forced smoking? not regular brandvery low n.

model srtm ? srtm Logan plot (use Logan slope from 5-40 and 45-90)

other calculations correlation images

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? yes no yes

best quote