Frontiers in Integrative Neuroscience www.frontiersin.org July 2010 | Volume 4 | Article 19 | 1
Original research article
published: 19 July 2010
or alcohol craving in drinkers (Sayette et al., 1994) can disrupt
performance of an unrelated reaction time task that requires cog-
The current study approached this hypothesis from an animal
learning perspective. As with humans, rats can select actions in a
voluntary, goal-directed manner. Their tendency to perform an
action, like pressing a lever, depends on the current incentive value
of the reward that would normally be produced by that action (cf.
Balleine and Ostlund, 2007; Balleine et al., 2009 for recent reviews).
We assessed whether the presence of contextual cues that signaled
alcohol intoxication would disrupt rats’ capacity for goal-directed
action selection. Rats were first given differential context condition-
ing such that one context was paired with ethanol injections and
a second, distinctive context was paired with saline injections. All
rats were then trained in a third, neutral context to press one lever
for grain pellets and different lever for sucrose pellets. They were
then administered a pair of choice tests, conducted in extinction,
to evaluate the rats’ ability to adjust their performance of the two
actions in response to a reduction in the value of one of the two food
outcomes. One test was conducted in the alcohol-paired context
and the other was conducted in the control (saline-paired) context.
If drug-paired cues interfere with goal-directed decision-making,
then rats should be capable of selecting actions based on the value
of their anticipated outcomes when tested in the control context but
should be impaired in doing so when tested in the ethanol-paired
Addiction may be viewed as a disorder of decision-making. Drug
addicts compulsively seek out and use drugs even though such
behavior can have devastating effects on their health and livelihood.
There is growing recognition among researchers that environmen-
tal cues that signal the availability of drugs play a role in supporting
pathological drug seeking in active drug users and in triggering
relapse in abstaining addicts (Stewart et al., 1984; Tiffany, 1990;
O’Brien et al., 1998). However, much remains unknown about how
drug-paired cues influence decision-making and behavioral control
processes more generally.
One explanation advanced by researchers from diverse theoreti-
cal backgrounds is that stimuli associated with drug use acquire
the capacity to interfere with cognitive processing (Tiffany, 1990),
rational decision-making (Bernheim and Rangel, 2004), or goal-
directed action selection (Ostlund and Balleine, 2008). Despite
important differences between these individual accounts, this gen-
eral hypothesis attempts to explain why under certain conditions
addicts can sometimes act in their own best interest by abstaining
from drug use but have difficulty doing so when confronted with
drug-paired cues. Importantly, this view predicts that such cues
should interfere with all actions requiring planning or deliberation,
not just those relating to drug use. In support of this claim, it has
been shown that imagery that provokes cigarette craving in smok-
ers (Sayette and Hufford, 1994; Cepeda-Benito and Tiffany, 1996)
Alcohol-paired contextual cues produce an immediate and
selective loss of goal-directed action in rats
Sean B. Ostlund1,2*, Nigel T. Maidment1,2 and Bernard W. Balleine2,3,4
1 Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, USA
2 The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA
3 Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA
4 Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia
We assessed whether the presence of contextual cues paired with alcohol would disrupt rats’
capacity to express appropriate goal-directed action control. Rats were first given differential
context conditioning such that one set of contextual cues was paired with the injection of
ethanol and a second, distinctive set of cues was paired with the injection of saline. All rats
were then trained in a third, neutral context to press one lever for grain pellets and another
lever for sucrose pellets. They were then given two extinction tests to evaluate their ability
to choose between the two actions in response to the devaluation of one of the two food
outcomes with one test conducted in the alcohol-paired context and the other conducted in
the control (saline-paired) context. In the control context, rats exhibited goal-directed action
control; i.e., they were able selectively to withhold the action that previously earned the now
devalued outcome. However, these same rats were impaired when tested in the alcohol-paired
context, performing both actions at the same rate regardless of the current value of their
respective outcomes. Subsequent testing revealed that the rats were capable of overcoming
this impairment if they were giving response-contingent feedback about the current value of
the food outcomes. These results provide a clear demonstration of the disruptive influence
that alcohol-paired cues can exert on decision-making in general and goal-directed action
selection and choice in particular.
Keywords: addiction, decision-making, habits, choice
Rui M. Costa, Instituto Gulbenkian de
Henry H. Yin, Duke University, USA
Simon Killcross, The University of New
South Wales, Australia
Sean B. Ostlund, Department of
Psychiatry and Biobehavioral Sciences,
University of California at Los Angeles,
Semel Institute for Neuroscience and
Human Behavior, Los Angeles, CA
Frontiers in Integrative Neuroscience www.frontiersin.org July 2010 | Volume 4 | Article 19 | 2
Ostlund et al. Alcohol-paired cues disrupt goal-directed action selection
context. To further characterize the predicted impairment, we also
assessed the effects of ethanol-paired cues on devaluation perform-
ance when rats were given response-contingent feedback about the
current outcome values.
MaterIals and Methods
All procedures were approved by UCLA’s Animal Research
subjects and apparatus
Adult (90–120 days) Long-Evans rats (Harlan Laboratories) were
used as subjects. Rats were housed in pairs in transparent plas-
tic tubs in a temperature- and humidity-controlled vivarium.
Experiments were conducted during the light phase of the 12:12-h
light/dark cycle. Tap water was always available when rats were in
their home cages. During instrumental conditioning and behavioral
testing, rats were food-deprived by restricting their daily allotment
of food to between 10–14 g of chow per day to maintain them at
approximately 85% of their free-feeding bodyweight. Behavioral
procedures were conducted in eight identical Med-Associates
operant chambers (standard modular chamber; interior length
30.5 cm, width 24.1 cm, height 21.0 cm), situated in sound- and
light-attenuated shells. The front and rear walls were composed of
aluminum paneling, and the ceiling, sidewall and hinged front door
were composed of transparent plexiglass. The floor consisted of 16
stainless steel rods. A waste pan containing corncob bedding was
placed under the grid floor. Each chamber had a pair of retractable
levers positioned to the left and right of a recessed food magazine,
into which grain and sucrose food pellets (Bioserv; 45 mg) could
be dispensed. An infrared beam crossed the magazine opening,
allowing for the detection of head entry responses. Each chamber
was also equipped with three infrared beams positioned 5 cm above
the grid floor across the length of chamber (one centered and oth-
ers 5 cm from each side wall) to measure activity in the horizontal
plane. A houselight located on the wall opposite the levers was
used to illuminate the chamber throughout all behavioral training/
The above description refers to the bare chamber, which served
at the training context during instrumental conditioning sessions.
During context conditioning and outcome devaluation test ses-
sions, we added visual, tactile, and olfactory cues to create two
distinctive contexts. For Context A, panels with black-and-white
horizontal stripes were positioned outside the transparent sidewall
and door, a plexiglass sheet covered with black, sandpaper-textured
adhesive-backed material (grip tape) covered the grid floor, and a
paper towel scented with 0.5 ml of a 10% artificial vanilla extract
solution (McCormick and Co. Inc., Baltimore, MD, USA) was
placed in the waste pan (below the floor). For Context B, white
panels with black filled circles were placed outside the sidewall
and door, the floor was covered with a white, diamond-textured
acrylic sheet, and a paper towel scented with 0.5 ml of 10% acetic
acid was placed in the waste pan.
For rats in Experiment 1 (N = 12), one context (either A or B) was
paired with an injection of ethanol solution (1 g/kg; 20% ethanol
in saline; i.p.) and the other context was paired with an injection of
an equivalent volume of buffered saline solution. Rats were exposed
to the two contexts in alternation over a period of 14 days (seven
exposures to each context). During context exposure sessions,
rats were placed in the context for 10 min, at which point they
were removed from the chamber and administered an injection
of the appropriate solution (either ethanol or saline). They were
then returned to the context for 60 min before being returned to
their home cage. A second group of rats (Experiment 2) was given
identical treatment except they received saline in both contexts.
This saline-only control group (N = 12) was used to assess the
characteristics of instrumental performance in rats that had no
experience with alcohol.
The food deprivation regimen was initiated 24 h after the last ses-
sion of context conditioning and was maintained throughout the
rest of the experiment. Rats were allowed to rest in their home cage
for 5 days between context conditioning and instrumental condi-
tioning. Two sessions of magazine training were then conducted.
During each session, 20 grain pellets and 20 sucrose pellets were
delivered according to a random time-30-s schedule. The rats were
then given 7 days of instrumental training. For the first 6 days of
training the two lever press actions were rewarded in separate daily
sessions with different outcomes. For half of the subjects in each
group, pressing the left lever earned grain pellets and pressing the
right lever earned sucrose pellets, whereas the remaining subjects
were trained using the opposite response–outcome relationships.
Each session started with the illumination of the house light and
the insertion of the left or right lever (session order was alter-
nated over days) and ended after 45 min or 30 pellets had been
earned, whichever came first. On the first 2 days of training, lever
pressing was continuously reinforced, such that every lever press
produced the appropriate outcome. The schedule of reinforce-
ment was then shifted to random ratio (RR)-5 for 2 days before
being shifted to a RR-10 schedule for the rest of training. During
the last day of instrumental conditioning rats were trained with
the same two action–outcome contingencies in alternating blocks
within a single session. At the beginning of the session, one of the
two levers (randomly determined for each rat) was inserted into
the chamber. Lever pressing was reinforced on a RR-10 schedule
until five outcomes were earned, at which point the lever was
retracted from the chamber. Three minutes later the other lever
was inserted until the rat had earned five presentations of the
other outcome. This cycle was repeated twice more, until each
outcome had been earned 15 times. This alternation training pro-
cedure was also used to reestablish responding between outcome
devaluation test sessions.
Rats were given two outcome devaluation tests to assess their ability
to respond in a goal-directed manner in the presence and in the
absence of alcohol-paired contextual cues. Outcome devaluation
was induced using a specific satiety procedure. Rats were given
60 min of unrestricted access to one of the two training outcomes in
their home cage immediately before each of the two tests. Half of the
rats in each group were sated on grain pellets and half were sated on
sucrose pellets, counterbalanced across context conditioning and
instrumental conditioning treatments. They were then placed in the
behavioral chamber, which was prepared as Context A or B. Each
Frontiers in Integrative Neuroscience www.frontiersin.org July 2010 | Volume 4 | Article 19 | 3
Ostlund et al. Alcohol-paired cues disrupt goal-directed action selection
test began with a 10-min context exposure period with the levers
retracted. The levers were then inserted for 5 min. Responses were
recorded but were not reinforced. After a session of retraining on the
two levers, rats were administered a second devaluation test that was
identical to the first except they were tested in the opposite context.
For half of the rats in each group, Test 1 was conducted in Context
A and Test 2 was conducted in Context B, whereas the other rats
were tested in the opposite order. Test order was counterbalanced
across earlier treatments. After another session of retraining with
the two action–outcome relationships, the rats were administered a
final test to assess whether alcohol-paired cues affected the expres-
sion of goal-directed action selection when response-contingent
feedback about goal value was provided. The rats were given 60 min
of access to the same outcome that was devalued in previous tests
before being placed in the chamber. For all alcohol-treated subjects
(Experiment 1), the chamber was prepared as the context that was
paired with alcohol. For saline-treated controls (Experiment 2), the
chamber was prepared as Context A or B, counterbalanced across
earlier treatments. After 10 min of context exposure, the two levers
were inserted into the chamber for 30 min and rats were allowed to
earn the two outcomes by lever pressing. Outcomes were delivered
contingently according to the action–outcome relationships used
during training, however a modified progressive ratio schedule of
reinforcement was used to encourage responding and sampling of
both action–outcome contingencies. For each action, the appro-
priate outcome was delivered after the first, third, sixth, 10th, and
15th lever press. All subsequent responses were then reinforced
according to a RR-10 schedule.
Locomotor activity during context conditioning sessions and out-
come devaluation tests was quantified as the total number of breaks
in three horizontal infrared beams. Instrumental performance dur-
ing outcome devaluation testing was expressed as a percentage of
baseline responding by dividing the response rate (presses per
minute) at test by the average response rate on that lever during
the most recent session of instrumental training.
The results from the context conditioning phase of Experiment 1
are presented in Figure 1. Panel A shows locomotor activity dur-
ing the 10-min period before each injection. Rats decreased their
activity in both the ethanol- and saline-paired contexts over days,
presumably due to habituation of the exploratory response to these
cues. A two-way repeated-measures ANOVA with drug (ethanol
vs. saline) and session (1–7) as factors found a significant effect
of session (F6,66 = 10.60; p < 0.001), but found no effect of drug
(F1,11 = 0.38; p = 0.55) or a drug by session interaction (F6,66 = 1.77;
p = 0.12). As can be seen in Panel B, which plots activity during
the 60-min post-injection period, rats displayed significantly lower
levels of locomotor activity after receiving ethanol injections than
after saline injections. This effect was relatively stable over ses-
sions. A two-way repeated-measures ANOVA with drug (ethanol
vs. saline) and session (1–7) as factors detected a significant main
effect of drug (F1,11 = 19.29; p < 0.001), a significant effect of ses-
sions (F6,66 = 2.22; p = 0.05), but found no interaction between
these factors (F6,66 = 0.90; p = 0.50).
FIgure 1 | Context conditioning and instrumental training results
(experiment 1). Mean photobeam breaks (± SEM) during the 10-min
pre-injection period (A) and the 60-min post-injection period (B) over days,
plotted separately for saline and ethanol injection sessions. Mean rate of lever
pressing (± SEM) over successive instrumental conditioning sessions (C).
Figure 1C presents the data from instrumental training sessions
for Experiment 1, plotted as the mean number of lever presses
performed per minute over days, averaged across the two actions.
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Ostlund et al. Alcohol-paired cues disrupt goal-directed action selection
(i.e., without explicit feedback about outcome value) and, as such,
the rats’ choice between actions depended on their memory of the
action–outcome relationships and of the updated values for those
outcomes. The results are presented in Figure 2, plotted separately
for the test conducted in ethanol-paired context (Panel A) and the
test conducted in the saline-paired context (Panel B). Rats exhibited
goal-directed choice in the saline-paired context, suppressing their
performance of the action that had earned the devalued outcome
while continuing to perform the other, non-devalued action at a
high rate. However, consistent with the hypothesis that drug-related
cues interfere with the expression of goal-directed action selection,
the same rats failed to show sensitivity to outcome devaluation
when tested in the ethanol-paired context. A three-way ANOVA
using context (ethanol-paired vs. saline-paired), action (devalued
All rats in this study had received the ethanol-treatment and all
successfully learned to lever press, increasing their rate of respond-
ing over sessions as the response requirement was increased (main
effect of session: F1,11 = 37.58; p < 0.001). The response rate for the
action whose outcome would be devalued at test (Mean 20.62;
SEM 3.08) did not significantly differ from that for the action
whose outcome would not be devalued (Mean 18.19; SEM 2.36)
(F1,11 = 1.31; p = 0.28).
devaluatIon testIng: no feedback
To assess whether ethanol-paired cues disrupt goal-directed action
selection, rats in Experiment 1 were administered two outcome deval-
uation tests, one conducted in the ethanol-paired context and the
other in the saline-paired context. These tests were given in extinction
FIgure 2 | effect of ethanol-paired contextual cues on the control of
instrumental performance in a test of outcome devaluation conducted in
extinction (i.e., without response-contingent feedback) (experiment 1).
Mean rate of responding (expressed as a percentage of pre-test baseline
responding, ± SEM) for the action trained with the devalued outcome and the
action trained with the other, non-devalued outcome (A). Rats exhibited
sensitivity to outcome devaluation when tested in the saline-paired context (left)
but did not show this effect when tested in the ethanol-paired context (right).
Mean locomotor activity (photobeam breaks, ± SEM) observed in the saline- and
ethanol-paired contexts during outcome devaluation testing (B).
Frontiers in Integrative Neuroscience www.frontiersin.org July 2010 | Volume 4 | Article 19 | 5
Ostlund et al. Alcohol-paired cues disrupt goal-directed action selection
deliveries, providing them with immediate feedback about the
relative value of the two rewards. Alternatively, it is possible that
cues signaling alcohol promote compulsive behavior, preventing
subjects from considering the consequences of their actions, even
when those consequences are experienced in a response-contingent
manner (see Section “Discussion”; Ostlund and Balleine, 2008). To
assess these two possibilities, all rats in Experiment 1 were given a
final outcome devaluation test in the ethanol-paired context, this
time with each action earning the appropriate outcome, as during
The data from this test are presented in Figure 3. Panel A plots
the rate of responding for the actions that produced the deval-
ued and non-devalued outcomes. Unlike when they were tested
vs. non-devalued) and time (min 1–5) as factors found a significant
main effect of time (F4,44 = 4.52; p = 0.004). The main effects of
action (F1,11 = 4.04; p = 0.07) and context (F1,11 = 2.01; p = 0.18)
were not significant. The action by time (F4,44 = 0.71; p = 0.59), con-
text by time (F4,44 = 2.33; p = 0.07), and context by action by time
(F4,44 = 0.45; p = 0.77) interactions also failed to reach significance.
Importantly, however, there was a significant interaction between
context and action (F1,11 = 4.76; p = 0.05), confirming that the rats’
choice between actions depended on which context they were in at
test. To further explore this effect, separate action by time ANOVAs
were conducted for each of the two context conditions. When tested
in the saline-paired context, the rats displayed sensitivity to outcome
devaluation (main effect of action: F1,11 = 5.31; p = 0.04) and showed a
significant reduction in responding over time (F4,44 = 5.64; p = 0.001)
due to extinction. However, when the tested in the ethanol-paired
context, the same rats showed no preference between the two actions
(F1,11 = 0.10; p = 0.76) and failed to significantly decrease their rate of
responding over minutes (F4,44 = 0.19; p = 0.94), which suggests that
these cues were also effective in disrupting the sensitivity of instru-
mental performance to extinction. The action by time interaction
did not reach significance in either context (saline-paired context:
F4,44 = 1.25; p = 0.30, ethanol-paired context: F4,44 = 0.10; p = 0.98).
Taken together, these findings demonstrate that environmental cues
that signal alcohol intoxication can acquire the ability to transiently
disrupt goal-directed action selection.
Figure 2C presents the rats’ locomotor activity during these tests.
Activity measures were taken starting 10-min before the levers were
inserted and finished after the 5-min test period. Levels of activity
were suppressed in the ethanol-paired context, relative to activity
in the saline-paired context. This effect was particularly clear dur-
ing the initial 10 min of the test, before the rats were allowed to
perform the lever press response. A repeated-measures ANOVA
performed on these data (first 10 bins) found a significant effect
of time (F9,99 = 22.06; p < 0.001), and a significant effect of context
(F1,11 = 4.64; p = 0.05). More importantly, we found a significant
time by context interaction (F9,99 = 2.70; p = 0.007), indicating
that the rats’ pattern of activity over time differed across the two
contexts. During the last 5 min, which covered the test of lever press
performance, the suppressive effects of the ethanol-paired context
were much less apparent (see Figure 3C). Statistical analysis of these
data (last five bins) found no effect of time (F1,11 = 0.34; p = 0.57) or
context (F4,44 = 1.26; p = 0.30), and found no interaction between
these factors (F4,44 = 0.77; p = 0.55).
outcoMe devaluatIon testIng: wIth feedback
The results of the first pair of outcome devaluation tests demonstrate
that ethanol-paired environmental cues can disrupt goal-directed
action selection. Importantly, no outcomes were delivered during
these tests, requiring subjects to rely on their memory of the action–
outcome contingencies that were present during training in order
to adjust their behavior in response to the change in outcome value.
Thus, the insensitivity to outcome devaluation found in the ethanol-
paired context may have been the result of a failure to retrieve the
appropriate action–outcome associations and/or a reliance on an
alternative response selection strategy (e.g., one based on stimulus-
response, or habit, learning). In either case, one might expect rats to
overcome this impairment if given response-contingent outcome
FIgure 3 | Sensitivity to outcome devaluation in the ethanol-paired
context in the rewarded test (i.e., with response-contingent feedback)
(experiment 1). Mean rate of lever pressing (percentage of baseline, ± SEM)
for the devalued and non-devalued outcomes (A). Rats displayed a selective
suppression in their performance of the action that earned the devalued
outcome at test, despite the presence of ethanol-paired cues. Mean
locomotor activity (photobeam breaks, ± SEM) observed during the rewarded
outcome devaluation test (B).
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Ostlund et al. Alcohol-paired cues disrupt goal-directed action selection
p < 0.001). The action by time interaction (F14,140 = 1.582; p = 0.09)
was not significant. The main effect of time suggests that the rats in
this experiment became sated on both rewards over the course of
the 30-min test, further reducing their rate of responding on both
actions. This is noteworthy because the rats in Experiment 1 showed
no effect of time when given a rewarded test in the alcohol-paired
context. Although one should be cautious when comparing results
across experiments, this finding suggests that the disruptive effects of
alcohol-paired cues on action selection may not be entirely reversed
by providing subjects with response-contingent feedback.
More importantly, however, the findings of Experiment 2 sug-
gest that alcohol-naïve rats tend to use a goal-directed strategy
when selecting instrumental actions under the current training and
without feedback, rats tested in the presence of ethanol-paired cues
exhibited sensitivity to outcome devaluation when the training out-
comes were contingently delivered. A two-way repeated- measures
ANOVA with action and time as factors found a significant
effect of action (F1,11 = 12.65; p = 0.005), but found no effect of
time (F14,154 = 1.03; p = 0.42) and no action by time interaction
(F14,154 = 0.68; p = 0.79).
Panel B plots the rats’ locomotor activity at test during the
10 min before and 30 min after the levers were inserted into the
chamber, plotted in 2-min bins. Activity levels appeared to decrease
rapidly before the lever was inserted (first five bins). Analysis of
these data using a repeated-measures ANOVA found a significant
main effect of time (F4,44 = 11.07; p < 0.001). Activity levels appeared
to remain relatively stable while the rats lever pressed. An ANOVA
conducted on these data (last 15 bins) found no effect of time
(F14,154 = 0.69; p = 0.78).
salIne-only control experIMent
The results presented above support the hypothesis that environ-
mental cues that have been paired with alcohol intoxication disrupt
the processes that mediate voluntary, goal-directed action selection.
However, this interpretation assumes that normal, ethanol-naïve rats
would rely on a goal-directed action selection strategy under the cur-
rent training and testing conditions. To characterize the instrumental
performance of ethanol-naïve subjects, a second group of rats under-
went the same context conditioning procedures as ethanol-treated
rats but received saline injections in both contexts. They were then
trained on the two action–outcome contingencies, as in the previous
experiment. One rat failed to complete instrumental training and was
excluded from the experiment (N = 11). By the last day of training,
the remaining rats reached response rates comparable to ethanol-
treated rats, and their rates of responding for the to-be devalued
(Mean 14.95; SEM 2.46) and non-devalued outcomes (Mean 18.82;
SEM 4.31) did not significantly differ (F1,10 = 2.26; p = 0.16).
Figure 4 presents the results of outcome devaluation testing. The
results from the tests conducted without response-contingent feed-
back are displayed in Panel A. Because both contexts were paired
with saline for all subjects, the data have been collapsed across tests.
As expected, the saline-only control group displayed clear evidence
of goal-directed action selection, selectively withholding their per-
formance of the action that, in training, had produced the outcome
that was devalued at test, relative to their performance of the other
action. A two-way repeated-measures ANOVA using action and
time as factors found a significant effect of action (F1,10 = 8.77;
p = 0.01) and of time (F4,40 = 3.94; p = 0.009). The action by time
interaction (F4,40 = 2.46; p = 0.06) failed to reach significance. This
finding is important because it establishes that alcohol-naïve rats
were capable of learning the relevant action–outcome associations
during training and were able to generalize these relationships
across contexts to guide their action selection at test.
The results of the outcome devaluation test conducted with
response-contingent feedback are presented in Panel B. Not sur-
prisingly, the saline-only treated rats continued to display sensitiv-
ity to outcome devaluation when their actions actually produced
the devalued and non-devalued outcomes. A two-way repeated-
measures ANOVA using action and time as factors detected a signifi-
cant effect of action (F1,10 = 6.67; p = 0.03) and of time (F14,140 = 4.71;
FIgure 4 | Outcome devaluation performance in saline-only treated rats
(experiment 2). Mean rate of lever pressing (percentage of baseline, ± SEM)
for the devalued and non-devalued outcomes in extinction (A) and rewarded
Frontiers in Integrative Neuroscience www.frontiersin.org July 2010 | Volume 4 | Article 19 | 7
Ostlund et al. Alcohol-paired cues disrupt goal-directed action selection
locomotor activity in the ethanol-paired context at test, which recent
findings suggest may be indicative of conditioned place aversion
learning (Hill et al., 2007). It is therefore prudent to consider the
possibility that an ethanol-induced conditioned place aversion may
have generated a competing behavior (e.g., freezing) that interfered
with the expression of instrumental performance, making it difficult
for us to evaluate whether this behavior was sensitive to outcome
devaluation or not. However, there are several features of our results
that are incompatible with this possibility. First, although the ethanol-
paired context was effective in suppressing activity at test, this effect
was limited to the period before the lever insertion; no differences in
activity were observed when the rats were actually pressing the levers.
Second, although the mean rate of lever pressing was numerically
lower in ethanol-paired context than in the saline-paired context,
this effect was not significant. Third, since response rates were not at
the behavioral floor (i.e., no presses on either lever) in the ethanol-
paired context, any competing response that did exist should not
have prevented the rats from displaying an outcome devaluation
effect, which involves selectively withholding whichever action had
earned the devalued outcome. Thus, even if the rats had responded
at a significantly lower rate in the ethanol-paired context, there was
sufficient responding to observe whether their choice between the
two levers was guided by goal-directed action selection.
Although this conditioned aversion-induced response competi-
tion account does not adequately explain the current results, it is
possible that aversive conditioning played some role in mediating
the influence of alcohol-paired cues over instrumental perform-
ance. Recent studies in rodents (Dias-Ferreira et al., 2009) and
humans (Schwabe and Wolf, 2009, in press) have demonstrated
that stress can promote habitual performance and/or interfere
with goal-directed action selection. Therefore, it is possible that
the disruption of goal-directed action selection produced by the
context paired with alcohol in the current study was mediated by
its tendency to evoke an acute stress response. This interpretation
is consistent with the widely held view that stress contributes to
drug relapse (Sinha, 2001; Lê and Shaham, 2002; Goeders, 2003)
and offers a novel behavioral mechanism through which it could be
exerting its effects. However, as the current study was not designed
to evaluate this hypothesis, further research will be needed to deter-
mine what, if any, role stress plays in mediating the disruptive effects
of alcohol-paired cues on instrumental action selection.
Recent years have seen considerable interest in theories of addic-
tion that attempt to explain the compulsive nature of drug seeking
through the effects of chronic drug use on brain systems respon-
sible for normal learning and memory. Some have suggested that
drug use leads to exaggerated habit formation, promoting the use
of stimulus-guided rather than outcome-guided action selection in
addicts (Tiffany, 1990; Berke and Hyman, 2000; Everitt et al., 2001).
Indeed, rats given repeated psychostimulant administration prior
to instrumental conditioning with natural food rewards have been
shown to display accelerated habit formation, indicating that such
treatment results in long-lasting adaptation in the neural circuitry
underlying this form of learning (Nelson and Killcross, 2006). In
contrast, the incentive sensitization theory of addiction (Robinson
and Berridge, 1993) proposes that repeated drug exposure results in
permanent alterations in the neural circuitry responsible for incentive
motivation, which, under normal conditions, allows stimuli associ-
testing conditions. Therefore it is reasonable to conclude that the
impaired outcome devaluation displayed by ethanol-treated rats in
the ethanol-paired context reflects a disruption of an action selec-
tion strategy that normally would have mediated their behavior.
The current study demonstrates that alcohol-paired environmen-
tal cues can disrupt decision-making; rats tested in a context that
signaled alcohol intoxication were found to lack the capacity to
select actions based on their anticipated outcomes. Importantly,
these rats were able to select their actions in a goal-directed manner
when tested in a different context that had not been paired with
alcohol, indicating that the influence of the alcohol-paired context
on action selection was transitory, and was therefore unlikely to
be the product of persistent neuroadaptions induced by the alco-
hol exposure regimen. The finding that the alcohol-paired con-
text failed to disrupt goal-directed performance when rats were
given response-contingent feedback about the current value of the
available outcomes provided further support for this conclusion.
This pattern of findings is therefore consistent with the hypothesis,
presented in the introduction, that cues associated with drugs or
alcohol can exert an acute, time-limited influence over decision-
making, interfering with the cognitive processes that support goal-
directed action selection and choice.
Although we found that ethanol-paired cues rendered instru-
mental performance insensitive to outcome devaluation, it is not
clear how these cues have their effect. It has been argued that drug-
related cues tax limited cognitive resources which are essential for
non-automatic decision-making, allowing automatic processes to
control performance (Tiffany, 1990). A similar distinction is made
in the field of instrumental conditioning, where it has been shown
that rats tend to select actions using either a goal-directed strategy
based on action–outcome learning or a habit strategy based on
stimulus-response learning (see Yin et al., 2008). Working from this
perspective, we have argued (Ostlund and Balleine, 2008) that drug-
paired cues might cause a transition from goal-directed to habitual
control, leaving instrumental performance insensitive to outcome
devaluation, an account that fits nicely with the results reported
here. Alternatively, rather than encouraging habitual performance,
it is possible that the alcohol-paired cues interfered with retrieval
or implementation of action–outcome associations, preventing rats
from using the current value of the two rewards to guide their choice
of actions. A third possibility is that the presence of cues signaling
alcohol intoxication caused a reappraisal of the two food outcomes
such that both outcomes were assigned equivalent, low incentive
values (e.g., by producing anhedonia). However, this account is
not consistent with our finding that rats exhibited sensitivity to
outcome devaluation when they were given response-contingent
feedback; this treatment should only have strengthened their assess-
ment that both outcomes were currently undesirable.
It is important to note that rats given pairings between environ-
mental cues and peripheral ethanol injections have been shown to
develop a conditioned aversion to those cues (Cunningham, 1979,
1981; van der Kooy et al., 1983; Bormann and Cunningham, 1998).
Our experimental preparation prevented us from directly measuring
our rats’ preference between the ethanol- and saline-paired con-
texts, but we did find that they displayed significantly lower levels of
Frontiers in Integrative Neuroscience www.frontiersin.org July 2010 | Volume 4 | Article 19 | 8 Download full-text
Ostlund et al. Alcohol-paired cues disrupt goal-directed action selection
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Conflict of Interest Statement: The
authors declare that the research was con-
ducted in the absence of any commercial or
financial relationships that could be con-
strued as a potential conflict of interest.
Received: 05 May 2010; paper pending pub-
lished: 17 June 2010; accepted: 25 June 2010;
published online: 19 July 2010.
Citation: Ostlund SB, Maidment NT and
Balleine BW (2010) Alcohol-paired con-
textual cues produce an immediate and
selective loss of goal-directed action in rats.
Front. Integr. Neurosci. 4:19. doi: 10.3389/
Copyright © 2010 Ostlund, Maidment
and Balleine. This is an open-access article
subject to an exclusive license agreement
between the authors and the Frontiers
Research Foundation, which permits unre-
stricted use, distribution, and reproduc-
tion in any medium, provided the original
authors and source are credited.
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The accelerated habit learning account predicts that if our repeated
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the insensitivity of action selection to outcome devaluation. Even if
both actions should have been performed at a higher rate (relative
to baseline conditions or when rats were tested in the saline-paired
context), one would still expect to observe higher rates of responding
on the action whose outcome remained valuable.
The current results may be particularly relevant to the early
stages of the addiction process. Experienced drug users are said to
display compulsive drug seeking if this behavior persists despite its
considerable adverse consequences. As argued elsewhere (Ostlund
and Balleine, 2008), this insensitivity to response-contingent pun-
ishment suggests that compulsive drug seeking may be dominated
by habitual control; such addicts lack the capacity to shift from
habitual to goal-directed performance when confronted by aversive
stimuli. However, the current findings demonstrate that drug-paired
cues can exert a more subtle, time-limited effect on instrumental
control. Although ethanol-paired cues were found to disrupt the rats’
tendency to selectively withhold an action whose outcome had been
devalued if tested without feedback (i.e., in extinction), this effect
was not observed when the devalued outcome was delivered at test,
which may be considered a form of punishment. Thus it appears
that context-alcohol learning can interfere with goal-directed action
selection without generating truly compulsive behavior. However,
even if transient and rapidly overcome, it is possible that exposure
to drug-related cues could promote drug use by obstructing the user
from considering the consequences of this behavior, thereby render-
ing action initiation more impulsive. This increased drug exposure
could, as a consequence, result in more persistent neuroadaptions,
facilitating the transition from drug abuse to addiction.
This research was supported by grant AA18014 from NIAAA
to Bernard Balleine and training fellowship T32 MH17140 to