wheel running as a predictor of cocaine self-administration and reinstatement in female rats
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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. Low- Responders. - PowerPoint PPT PresentationTRANSCRIPT
Wheel running as a predictor of cocaine self-administration and reinstatement in female rats
Larson and Carroll (2005)Presented byAmanda Jonas
High-RespondersPalatable tastesNovelty-seeking ImpulsivityStress reactivity
High-Responders vs. Low- RespondersMore sensitive to the locomotor effects
of drugs of abuseMore likely to self-administer drugs
Wheel RunningNondrug behavior actively engaged in
by ratsReinforcing effects similar to drugsRats will lever press for access Show conditioned place preferenceEscalate wheel running when given
unlimited access
Wheel Running and Vulnerability to drugsWheel 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 locomotor-activating 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 2Compare HiR and LoR rats on the
cocaine self-administration behavior during maintenance
Hypthesis: HiR rats will self-administer more cocaine than LoR rats
Objective 3Compare 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
Animals14 sexually mature female Wistar rats250-340 gFemales more active in running wheels
than malesEstrous 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 conditionsAll rooms on 12/12 light/dark cycle Lights on at 0600 hAcclimated for 3 days priors to surgeryHoused in experimental chambers
ApparatusStainess 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 chamberChambers 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 wheelEvery 4 sensor breaks were counted as
one wheel revolution
CocaineDissolved in 0.9% NaCl solution along
with heparinRats 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 activityPrior to running wheel access, tested in
the circular track for 45 min for 2 daysLocomotor activity was significantly
lower on day 2 than day 1Day 1 reflects the locomotor response
to noveltyDay 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
SurgeryRats were implanted with jugular
catheters for i.v. cocaine self-administration
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 procedureRats 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
ReinstatementTesting 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 drug-seeking 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
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