Transcript Amanda Jonas - USD Biology

Wheel running as a predictor
of cocaine self-administration
and reinstatement in female
rats
Larson and Carroll (2005)
Presented by
Amanda Jonas
High-Responders
 Palatable
tastes
 Novelty-seeking
 Impulsivity
 Stress reactivity
High-Responders vs. LowResponders
 More
sensitive to the locomotor effects
of drugs of abuse
 More likely to self-administer drugs
Wheel Running
 Nondrug
behavior actively engaged in
by rats
 Reinforcing effects similar to drugs
 Rats will lever press for access
 Show conditioned place preference
 Escalate wheel running when given
unlimited access
Wheel Running and
Vulnerability to drugs
 Wheel
running experience produced
cross-tolerance to the rewarding effects
of morphine
 Access during ethanol withdrawal
potentiated subsequent ethanol intake
Objective 1 of the current
study

Determine whether individual differences in
voluntary wheel running predicted the
subsequent sensitivity to the locomotoractivating effects of cocaine
 Hypothesis: High-Responder (HiR) rats will
show greater locomotor activity in response
to an acute injection of cocaine compared to
Low-Responder (LoR) rats
Objective 2
 Compare
HiR and LoR rats on the
cocaine self-administration behavior
during maintenance
 Hypthesis: HiR rats will self-administer
more cocaine than LoR rats
Objective 3
 Compare
HiR and LoR rats on their
cocaine-seeking behavior during
extinction and reinforcement
 Determine whether HiR rats are more
motivated than LoR rats to seek cocaine
under extended abstinence conditions
Animals
 14
sexually mature female Wistar rats
 250-340 g
 Females more active in running wheels
than males
 Estrous cycles were allowed to vary
randomly and were not monitored or
analyzed
Food

Food and water were available as libitum until
surgery
 After surgery it was reduced to 16 g/day and
remained that amount for the rest of the
experiment
 Food restriction used to accelerate training
and to control potential difference in food
intake between groups
Other conditions
 All
rooms on 12/12 light/dark cycle
 Lights on at 0600 h
 Acclimated for 3 days priors to surgery
 Housed in experimental chambers
Apparatus
 Stainess
steel locomotor tracks
 Used to measure novelty-induced
locomotor activity, baseline locomotor
activity, and locomotor activity after
acute exposure to either saline or
cocaine
 Tracks had inner and outer diameters of
46 and 71 cm
Apparatus continues

Walls were 25 cm high
 Tracks covered with Plexiglas sheet during
testing
 Four infrared sensors mounted above the
floor of the track on the outer wall at 0º, 90º,
180º, and 270º
 Two successive sensor interruptions were
measured as one activity count and counts
were totaled and recorded in 5-min
increments
Wheel Running and i.v.
cocaine self-administration

Octagonal operant chamber enclosed w/ a
fan for white noise and ventilation
 Eight walls alternated with stainless steel or
Plexiglas
 Two response levers on two of the steel
panels
 Stimulus light located above each lever and
illuminated for 20-s after each lever press
SA chamber
 Chambers
also contained a ceiling
house light, a food hopper, and a panel
for the water bottle
 Chamber had guillotine-style door which
allowed access to a running wheel
 Four sensors located along the wheel
 Every 4 sensor breaks were counted as
one wheel revolution
Cocaine
 Dissolved
in 0.9% NaCl solution along
with heparin
 Rats received cocaine (0.4 mg/kg/inf) at
a rate of 0.025 ml/s and a duration of 1
s/100g body weight
Figure 1: Wheel running
Assessment of locomotor
response activity
 Prior
to running wheel access, tested in
the circular track for 45 min for 2 days
 Locomotor activity was significantly
lower on day 2 than day 1
 Day 1 reflects the locomotor response
to novelty
 Day 2 reflects baseline activity levels
Figure 2 : Day 1
Figure 2: Day 2
Wheel Running and locomotor
response to cocaine

Allowed access to wheel for 21 days, 6 h/day
 Wheel access was then discontinued
 Median split used to divide rats into HiR and
LoR groups
 The two groups were retested on the circular
track for 2 days, 7 days after no wheel access
 First day-i.p. injection of saline prior to track
 Second day- 10 mg/kg cocaine i.p. injection
Figure 3
Figure 4: Mean activity
Figure 4: Mean overall activity
Surgery
 Rats
were implanted with jugular
catheters for i.v. cocaine selfadministration
 3 days of recovery
Figure 1: SA
SA training

Trained to self-administer cocaine in 2 h daily
sessions
 When active or inactive lever pressed,
stimulus lights lit for 20 s
 Active lever resulted in cocaine infusion
 Active lever initially baited with peanut butter
and rats given 2 cocaine priming injections at
the beginning of each session
 PB and priming discontinued after rats
administered greater than 20 infusions for 3
days
Maintenance
 If
lever pressing maintained, rats tested
in reinstatement procedure
 Rats allowed to lever press for 14 days
during 2-h sessions
Figure 5
Extinction

Saline was substituted for cocaine and
behavior extinguished over the next 21 days
 All other stimulus conditions remained the
same
 Drug pumps and stimulus lights were
unplugged for 3 days
 After 3 days of extinction without cues,
reinstatement testing commenced
Figure 6
Reinstatement
 Testing
consisted of 6 days of
alternating saline and cocaine priming
injections
 One injection (either cocaine or saline)
was given at the beginning of each 2-h
session
Figure 7
Discussion

HiR rats had greater cocaine SA during
maintenance and cocaine-induced
reinstatement of lever responding
 Rats did not differ in their locomotor response
(novel and baseline)
 Results indicated that individual differences in
wheel running predicted the subsequent
vulnerability for cocaine SA and
reinstatement
Discussion continued

Suggests that HiR rats more motivated for
cocaine-seeking during ongoing SA as well
as during reinstatement
 HiR were not more sensitive than LoR rats to
the locomotor-activating effects of cocaine
 HiR had an enhanced response to locomotor
activating effects of cocaine and cocaine SA
during maintenance
Discussion continued
HiR’s for nondrug rewards are motivated to
self-administer psychostimulant drugs
 Escalation: a key feature of drug addiction,
increased performance may reflect attempt to
compensate for tolerance to the rewarding
aspects of these behaviors and may occur
with other nondrug rewards such as wheel
running
 HiR rats may SA more cocaine in
maintenance to compensate for higher levels
of deprivation of the wheel reward

Discussion continued

No group differences in extinction
 Study shows that wheel running predicts
vulnerability to the reinstatement of drugseeking behavior after an extended
abstinence period
 May lead to screening methods for identifying
at-risk drug users and may aid in developing
prevention strategies based on specific
vulnerabilities
Thank You!