Transcript What do we know about addictive drugs from animal studies?

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.”
Carboni, … DiChiara et al. J Neurosci 20:RC102(1-5), 2000
aaarrrggghhhh!!!!! – show me DBP
what phenomenon is this?
from: Schultz, Dayan, & Montague, 1997, Science.
No CS
unexpected
reward
CS
predicted
reward
CS
absence of
predicted reward
does everyone understand what they are showing here?
-12
-2
de-nic cig
40
nic cig
50
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)
phenomenon to test
smoking
smoking
intra-subject (1 scan – 2
different cigs)
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 smoke 3-6 cigarettes INSIDE
scanner
scanner
timing
smoke-break @ t=50min –
60 min
smoke every 12 min start@ -15 -12-8 (denic) and 40-60
mn
(nic)
self-admin
yes
forced smoking
(some aversion)
yes
cigarette type
high/low nic
own brand
finding in Ventr Str
DBP corr w/ craving
(reduction? all +)
none
finding in Dorsal Str
none?
DBP related to pleasure (+,-)
high nic / low nic
(research)
yes “ventr basal ganglia”
corr with dependence
score
no
in scanner nic--- and denic
(control) cigs
Brody
Barrett
Scott
limitations
•movement
•forced smoking
•low n
•aversion to cigs
•low resolution scanner •low n
forced smoking? not regular
brand
very low n.
model
srtm ?
Logan plot (use Logan slope
from 5-40 and 45-90)
srtm
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
no
yes
order effects?
best quote
yes