Hosking, JG, Floresco, SB, and Winstanley, CA –
Dopamine and mental versus physical effort
Supplementary Information
Supplementary Methods
Subjects
Subjects were 55 male Long-Evans rats from Charles Rivers Laboratories (St. Constant, Quebec,
Canada), and each weighed 275-300g at the beginning of the experiment. Animals were food
restricted to 14-16g rat chow per day and maintained at ~85% of their free-feeding weight.
Water was available ad libitum. Animals were pair housed in a climate-controlled colony room
on a 12hr reverse light-dark cycle (lights off: 8:00am; temperature: 21°C). All housing and
testing was in accordance with the Canadian Council of Animal Care, and all procedures were
approved by the University of British Columbia’s Animal Care Committee.
Behavioral testing
All testing took place within 16 standard five-hole operant chambers, each supplemented with
two retractable response levers and enclosed in a ventilated, sound-attenuating cabinet (Med
Associates Inc., Vermont, USA). The chambers were controlled by software written in Med-PC
by CAW (rat Cognitive Effort Task) and Stan D. Floresco (Effort Discounting Task), running on
an IBM-compatible computer.
Habituation and pre-task training
Hosking JG/ Winstanley CA
Figure 1a depicts the experimental timeline. All animals were habituated and trained for the
rCET as previously described (see Cocker et al, 2012a, including supplementary methods). In
brief, animals first learned to make a nosepoke response in an illuminated aperture within 5s to
obtain a sucrose pellet reward (Bioserv, 45mg), as per five-choice serial reaction time task
(5CSRTT) training (Winstanley et al, 2010). In subsequent sessions, animals were trained to
respond on both of the response levers at a fixed ratio 1 (FR1) schedule for reward. Animals
were then trained on a forced-choice variant of the rCET (40-50 sessions), wherein only a single
lever extended, before the standard free-choice program.
The rat Cognitive Effort Task (rCET)
The rCET has been previously described in detail (Cocker et al, 2012a) and a schematic of the
trial structure and subsequent reinforcement is presented in Figure 1b. Briefly, animals were
tested 4-5 days per week in 30min sessions of no fixed trial limit. At the outset of training, the
levers were permanently designated to initiate either low-effort/low-reward (LR) or higheffort/high-reward (HR) trials, and these designations were evenly counterbalanced across
subjects. A new trial was available when the food-tray light was illuminated. A nosepoke in the
food tray extinguished the light and extended the levers. When animals pressed one of the
levers, thereby choosing a LR or HR trial, both levers retracted and a 5s inter-trial interval (ITI)
began. Following the ITI, one of the five stimulus lights briefly illuminated, with a stimulus
duration (SD) of 1.0s for a LR trial and 0.2s for a HR trial. Animals then had 5s to nosepoke
within the previously illuminated aperture (a correct response) for reward. Animals were
rewarded with 1 sugar pellet for a correct LR trial and 2 sugar pellets for a correct HR trial.
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Upon delivery of reward, the tray light again illuminated to signal the opportunity to start the
next trial.
Trials went unrewarded for a number of reasons: if animals failed to make a lever
response within 10s (a choice omission); if animals nosepoked during the ITI (a premature
response, an oft-reported measure of motor impulsivity; Robbins, 2002); if animals nosepoked in
any aperture other than the one that was illuminated (an incorrect response); and if animals failed
to nosepoke at the array within 5s after stimulus-light illumination (a response omission). All
such behaviors were punished with a 5s time-out period, accompanied by illumination of the
house light. During the time-out, new trials could not be initiated and thus reward could not be
earned. Following the time-out, the house light extinguished and the tray light illuminated to
signal that the rat could begin the next trial.
Behavioral measurements for the rCET
Percent choice (rather than the absolute number of choices) was used to determine preference for
lever/trial type, in order to minimize the influence of variation in the number of trials completed.
Percent choice was calculated as follows: (number of choices of a particular lever / total number
of choices) * 100. When baseline performance on the rCET was deemed statistically stable (i.e.
no effect of session on repeated-measures ANOVA for choice, accuracy, and premature
responding over the last three sessions; see “Data analysis” below), the mean choice of the HR
option was 73%. Animals were grouped as “workers” if they chose HR for > 70% of trials (n =
40) and as “slackers” if they chose HR for ≤ 70% of trials (n = 15). This subdivision was based
on the mean split from the original rCET paper (Cocker et al, 2012a), where workers and
slackers were categorized based on their preference for greater than or less than the average of
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70% HR trials. To maintain consistency when discussing individual differences and to avoid
arbitrary categorization, we therefore held the worker/slacker distinction at 70% HR trials for
this study.
The following variables were also analyzed separately for LR and HR trials: percent
accuracy ((number of correct responses / number of total responses made) * 100); percent
response omissions ((number of trials omitted / number of correct, incorrect, and omitted trials) *
100); percent premature responses ((number of premature responses / total number of trials
initiated) * 100); latency to choose between the LR and HR levers (lever choice latency); latency
to correctly nosepoke in the illuminated aperture (correct latency); latency to collect reward
(collection latency). Failures to choose a lever at the beginning of the trial (choice omissions)
and the total number of completed trials were also analyzed.
The (physical) Effort-Discounting Task (EDT)
The cohort was divided in half once baseline behavior on the rCET had stabilized (30-35 freechoice sessions); 28 animals remained on the rCET (workers: n = 20; slackers: n = 8) while 27
animals were switched to the EDT (workers: n = 20; slackers: n = 7), a physical-effort decisionmaking task that has been developed and well-described elsewhere (e.g. Floresco et al, 2008).
Within the EDT, animals received 48 trials per 32min session, divided equally into four blocks
(Figure 1c). Each block started with two forced-choice trials, in which a single presentation of
each option (lever) was given, followed by ten free-choice trials. Unlike the rCET, new trials
were not initiated by the animal but rather were presented every 40s with illumination of the tray
light, followed 3s later by the extension of the levers. Levers were permanently designated as
either LR or HR, and these contingencies were reversed from the rCET to avoid the confound of
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perseverative responding from one task to the other. If animals responded on the LR lever, both
levers retracted and the animal immediately received 2 sugar pellets; this cost (i.e. a single lever
press, FR1) remained constant for LR trials across the session. If animals responded on the HR
lever, the LR lever retracted and animals were given 25s to complete a higher number of presses
for 4 sugar pellets. The HR costs increased across the session, beginning with FR2 in the first
block, followed by FR5, FR10, and finally FR20 in the last block.
Animals did not receive reward if they did not make a choice between levers (choice
omission) or if they failed to complete the required number of lever presses for a HR trial
(incomplete HR response). As animals were experienced in lever pressing to obtain reward,
choice omissions and incomplete HR responses occurred less than once per session per animal
from the outset, and were virtually absent by the end of baseline EDT (15 sessions).
Behavioral measurements for the EDT
To parallel rCET data, percent choice was used for LR or HR options/levers in each block:
(number of choices of a particular lever in a given block / total number of choices in a given
block) * 100. Average latency to complete HR choices (choice latency) was measured. Choice
omissions and incomplete HR responses were also analyzed.
Following the establishment of baseline behavior, four animals no longer sampled from
both options/levers, instead pressing the LR lever exclusively. Due to this inflexibility of
behavior, these animals were removed from subsequent analyses. Furthermore, one animal was
removed from the study due to unexpected, unrelated health complications, leaving a total of 22
animals in this subgroup (workers: n = 16; slackers: n = 6) for the drug challenges.
Pharmacological challenges
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Upon stable baseline behavior in each respective task, drugs were administered in the following
order: the dopamine D2 antagonist eticlopride (0, 0.01, 0.03, 0.06mg/kg), dopamine D1
antagonist SCH23390 (0, 0.001, 0.003, 0.01mg/kg), the α2-adrenergic receptor antagonist
yohimbine (0, 1, 2, 5mg/kg), and the selective norepinephrine reuptake inhibitor atomoxetine (0,
0.1, 0.3, 1.0mg/kg). S-(−)-Eticlopride hydrochloride, R(+)-SCH-23390 hydrochloride, and
yohimbine hydrochloride were purchased from Sigma-Aldrich Canada (Oakville, ON, Canada);
tomoxetine hydrochloride was purchased from Tocris (Minneapolis, MN, USA). Eticlopride,
SCH23390, and atomoxetine were dissolved in 0.9% sterile saline, and yohimbine was dissolved
in distilled water. All drugs were administered in a volume of 1ml/kg via intraperitoneal
injection. Animals were given a minimum of one week drug-free testing between compounds to
minimize any carryover effects.
All drugs were prepared fresh daily, and administration adhered to a digram-balanced
Latin Square design (for doses A-D: ABCD, BDAC, CABD, DCBA (p. 329, Cardinal and
Aitken, 2006)). The three-day injection schedule started with a baseline session, followed by a
drug or saline injection session, and then by a non-testing day. Injections for eticlopride,
SCH23390, and yohimbine were administered 10min before behavioral testing; atomoxetine
injections were administered 45 minutes before testing.
Data analysis
All data were analyzed in SPSS (version 16.0; SPSS/IBM, Chicago, IL, USA). All variables
expressed as a percentage were arcsine transformed to minimize artificial ceiling effects (Zeeb et
al, 2009). Data were analyzed using repeated-measures ANOVA with choice (two levels: LR or
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HR), session (three levels: baseline sessions 1-3), and dose (four levels: saline plus three drug
doses) as within-subjects factors, and block (four levels: FR2, FR5, FR10, FR20) was an
additional within-subjects factor for the EDT. Group (two levels: worker or slacker) was used
throughout the experiment as a between-subjects factor in all analyses. Groups proved
extraordinarily stable across the experiment: at rCET baseline, all saline conditions for rCET
drug challenges, and post-drug baseline, workers chose a significantly greater percentage of HR
trials than slackers (group: all Fs > 28.067, p < 0.001). Any main effects of significance (p <
0.05) were further analyzed via post-hoc one-way ANOVA or paired-samples t-tests. Any pvalues > 0.05 but < 0.07 were reported as a statistical trend.
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Supplementary Results
rCET: Eticlopride administration
Choice behavior, accuracy, and premature responses. Baseline behavior for the rCET has been
previously discussed at length (Cocker et al, 2012b; Hosking et al, 2014), and as such will only
be cursorily addressed here. As per previous cohorts, animals chose high-effort/high-reward
(HR) trials more than low-effort/low-reward (LR) trials following saline injection (saline only—
choice: F1,26 = 13.461, p = 0.001), with substantial individual variation across the group; as per
their baseline designations, workers chose a significantly higher proportion of HR trials than
slackers (group: F1,26 = 40.814, p < 0.001). The dopamine D2 receptor antagonist eticlopride had
no effect on animals’ choice of LR or HR trials (Figure 2a; dose: F3,78 = 1.222, NS).
As expected, animals were more accurate (i.e. demonstrated better performance) on LR
versus HR trials (saline only—choice: F1,26 = 21.657, p < 0.001). As per previous cohorts,
workers and slackers performed the rCET equally well (saline only—group / choice x group: all
Fs < 1.350, NS). This reiterates that choice preferences were not driven solely by individuals’
ability to perform the task. Eticlopride had no effect on animals’ accuracy (Figure 2b; dose / dose
x group / choice x dose / choice x dose x group: all Fs < 2.230, NS).
In general, premature responding was higher for HR versus LR trials (choice: F1,26 =
4.511, p = 0.043) but there were no differences in premature responding between workers and
slackers (group / choice x group: all Fs < 0.809, NS), indicating that choice preferences were not
driven by individuals’ motor impulsivity. Eticlopride had no effect on animals’ rates of
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premature responding (Figure 2c; dose / dose x group / choice x dose / choice x dose x group: all
Fs < 1.489, NS).
Other behavioral measures. Eticlopride had no effect on the amount of time animals took
to choose between LR and HR levers (dose / choice x dose: all Fs < 1.525, NS), and no
differences in this choice latency were observed between workers and slackers (group / dose x
group / choice x dose x group: all Fs < 0.521, NS). Animals took equally long to choose between
LR and HR options (saline only—choice: F1,26 = 0.120), although there was a trend for animals
to choose their preference (e.g. HR for workers) faster (saline only—choice x group: F1,26 =
4.039, p = 0.055; —workers only / —slackers only—choice: all Fs < 3.460, NS). Eticlopride
significantly increased the time taken to make a correct nosepoke response, for all animals across
both trial types (dose: F3,78 = 3.030, p = 0.034; dose x group / choice x dose / choice x dose x
group / group: all Fs < 1.243, NS). Correct responses were equally fast for LR versus HR trials,
for workers and slackers (saline only—choice / choice x group / group: all Fs < 2.441, NS). As
previously reported, all animals collect reward faster following HR trials versus LR trials (saline
only—choice: F1,26 = 41.959; choice x group: F1,26 = 2.229, NS), with a trend for slackers to
collect reward faster than workers (group: F1,26 = 3.988, p = 0.056); as previously discussed
(Cocker et al, 2012b), this suggests that slackers understand the contingencies of the task and are
not indifferent to reward magnitude, despite their reduced preference for high-effort trials.
Eticlopride had no main effect on this collection latency (dose / dose x group / choice x dose: all
Fs < 2.514, NS; choice x dose x group: F3,78 = 4.079, p = 0.028; workers only—LR / HR,
slackers only—LR / HR —dose: all Fs < 1.885, NS). All animals failed to respond by nosepoke
equally for LR versus HR (saline only—choice / choice x group / group: all Fs < 0.773, NS).
Eticlopride increased these response omissions for all animals across all trial types (dose: F3,78 =
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6.300, p = 0.003; dose x group / choice x dose / choice x dose x group: all Fs < 2.150, NS).
Eticlopride also dose-dependently increased the number of lever (choice) omissions for all
animals (dose: F3,78 = 4.201, p = 0.038; dose x group / group: all Fs < 0.394, NS) and decreased
the number of completed trials for all animals (dose: F3,78 = 9.358, p = 0.002; dose x group /
group: all Fs < 0.598, NS).
rCET: SCH23390 administration
Choice behavior, accuracy, and premature responses. The dopamine D1 receptor antagonist
SCH23390 had no effect on choice, accuracy, or premature responding for the rCET (Figure 2df; dose / dose x group / choice x dose / choice x dose x group: all Fs < 2.132, NS).
Other behavioral measures. For all animals, SCH23390 increased the latency to choose
between LR and HR levers/options (dose: F3,78 = 5.245, p = 0.002; dose x group / choice x dose /
choice x dose x group: all Fs < 1.744, NS). In general, SCH23390 had an U-shaped effect on
correct nosepoke responding: the lowest dose shortened correct latency, while the highest dose
lengthened it (dose: F3,78 = 6.186, p = 0.009; dose x group: F3,78 = 6.367, p = 0.001; choice x
dose: F3,78 = 5.059, p = 0.019; choice x dose x group: F3,78 = 3.242, p = 0.026; workers only—
dose: F3,57 = 5.273, p = 0.003; —saline vs low—dose: F1,19 =16.311, p = 0.001; —saline vs
med—dose: F1,19 = 2.972, NS; —saline vs high—dose: F1,19 = 4.535, p = 0.047; slackers only—
dose: F3,21 = 2.803, NS). SCH23390 had no effect on the latency to collect reward following a
successful trial (dose / dose x group / choice x dose / choice x dose x group: all Fs < 0.302, NS).
SCH23390 also increased nosepoke response omissions for all animals across both trial types
(dose: F3,78 = 4.447, p = 0.024; dose x group / choice x dose / choice x dose x group: all Fs <
1.628, NS) but had no effect on lever (choice) omissions (dose / dose x group: all Fs < 0.675,
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NS). Finally, SCH23390 decreased the number of completed trials for all animals (dose: F3,78 =
10.864, p = 0.002; dose x group: F3,78 = 0.390, NS).
rCET: Yohimbine administration
Choice behavior, accuracy, and premature responses. The α2-adrenergic receptor antagonist
yohimbine did not affect animals’ choice behavior (Figure 2g) or premature responding (Figure
2i; dose / dose x group: all Fs < 0.978, NS). For all animals across both trial types, however,
yohimbine dose-dependently decreased accuracy, an effect that achieved significance at the
highest dose (Figure 2h; dose: F3,78 = 7.314, p = 0.006; dose x group / choice x dose / choice x
dose x group: all Fs < 2.276, NS; saline vs low—dose: F1,26 = 2.948, NS; saline vs med—dose:
F1,26 = 3.665, p = 0.067; saline vs high—dose: F1,26 = 13.640, p = 0.001).
Other behavioral measures. Yohimbine had a U-shaped effect on the time taken by all
animals to choose between LR and HR levers: the low and intermediate doses shortened choice
latency, while the highest dose did not differ from saline (dose: F3,78 = 11.434, p < 0.001; dose x
group / choice x dose: all Fs < 1.344, NS; choice x dose x group: F3,78 = 3.210, p = 0.053; saline
vs low—dose: F1,26 = 35.029, p < 0.001; saline vs med—dose: F1,26 = 8.740, p = 0.007; saline vs
high—dose: F1,26 = 1.162, NS). Latency to make a correct nosepoke response demonstrated a
similar U-shaped effect to yohimbine, with low and intermediate doses shortening correct
latency, while the high dose did not differ from saline (dose: F3,78 = 4.546, p = 0.035; dose x
group / choice x dose / choice x dose x group: all Fs < 1.761, NS; saline vs low—dose: F1,26 =
8.682, p = 0.007; saline vs med—dose: F1,26 = 8.709, p = 0.007; saline vs high—dose: F1,26 =
2.241, NS). For all animals on both trial types, yohimbine also speeded latency to collect reward
following successful trials (dose: F3,78 = 5.021, p = 0.010; dose x group / choice x dose / choice x
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dose x group: all Fs < 0.640, NS). Yohimbine modestly decreased nosepoke response omissions
at the lowest dose, and dramatically increased response omissions at the highest dose (dose: F3,78
= 19.749, p < 0.001; dose x group / choice x dose x group: all Fs < 2.353, NS; choice x dose:
F3,78 = 3.008, p = 0.059; saline vs low—dose: F1,26 = 4.313, p = 0.048; saline vs med—dose: F1,26
= 0.074, NS; saline vs high—dose: F1,26 = 20.621, p < 0.001). Similarly, the highest dose of
yohimbine increased lever (choice) omissions for all animals, while the low and intermediate
doses had no effect (dose: F3,78 = 15.428, p < 0.001; dose x group: F3,78 = 0.027, NS; saline vs
low / saline vs med—dose: all Fs < 1.189, NS; saline vs high—dose: F1,26 = 15.269, p = 0.001).
Interestingly, the low and intermediate doses of yohimbine increased the number of completed
trials for all animals, while the highest dose of yohimbine greatly decreased trials (dose: F3,78 =
36.211, p < 0.001; dose x group: F3,78 = 1.341, NS; saline vs low—dose: F1,26 = 27.365, p <
0.001; saline vs med—dose: F1,26 = 6.269, p = 0.019; saline vs high—dose: F1,26 = 29.316, p <
0.001).
rCET: Atomoxetine administration
Choice behavior, accuracy, and premature responses. The selective norepinephrine reuptake
inhibitor atomoxetine had no effect on animals’ choice (Figure 2j) and premature responding
(Figure 2l; dose / dose x group / choice x dose / choice x dose x group: all Fs < 1.680, NS) and
virtually no effect on accuracy, with only a trend to decrease workers’ performance on LR trials
(Figure 2k; dose / dose x group / choice x dose: all Fs < 2.172, NS; choice x dose x group: F3,78 =
3.124, p = 0.031; workers only—LR only—dose: F3,57 = 3.141, p = 0.066; workers only—HR
only / slackers only—LR / HR—dose: all Fs < 1.252, NS).
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Other behavioral measures. For all animals across both trial types, atomoxetine increased
the time needed to choose between the LR and HR levers/options (dose: F3,78 = 4.400, p = 0.007;
dose x group / choice x dose / choice x dose x group: all Fs < 0.992, NS). Atomoxetine did not
affect the latency to make a correct nosepoke response, save for a trend increase slackers’ HR
correct response latency at the lowest dose (dose / dose x group / choice x dose: all Fs < 0.716,
NS; choice x dose x group: F3,78 = 3.554, p = 0.018; workers only—LR / HR / slackers only—
LR—dose: all Fs < 1.813, NS; slackers only—HR only—dose: F3,21 = 2.741, p = 0.069).
Atomoxetine also had no effect on collection latency (dose / dose x group / choice x dose /
choice x dose x group: all Fs <1.603, NS) or response omissions (dose / dose x group / choice x
dose / choice x dose x group: all Fs < 1.896, NS) but modestly increased lever (choice)
omissions (dose: F3,78 = 3.779, p = 0.050; dose x group: F3,78 = 0.859, NS) and decreased the
number of completed trials (dose: F3,78 = 11.803, p < 0.001; dose x group: F3,78 = 0.231, NS).
EDT: baseline behavior and comparison to rCET
Upon switching to the EDT, animals demonstrated high performance during the first three
sessions, with less than one incomplete HR trial per animal per session, on average, and virtually
zero choice omissions. Furthermore, while choice behavior was not yet stable (session: F2,50 =
10.628, p = 0.001), all animals demonstrated sensitivity to the physical effort costs, as choice of
HR decreased across blocks as the costs increased (Figure 3a; block: F3,75 = 8.333, p = 0.001;
block x group: F3,75 = 0.510, NS). Remarkably, and despite reversing the lever/reward
contingencies from the rCET to the EDT, the worker/slacker distinction held during these early
sessions of the EDT: animals that had been deemed “workers” for the rCET remained workers
for the EDT, and likewise for slackers (group: F1,25 = 6.351, p = 0.018). Baseline choice behavior
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on the rCET was linearly correlated with choice behavior on sessions 1-3 of the EDT (Figure 3b;
adjusted r2 = 0.358, p = 0.001).
However, upon reaching stability at sessions 13-15 (session / session x block / session x
block x group: all Fs < 1.359, NS), the worker/slacker distinction was no longer valid for the
EDT (Figure 3c; group: F1,25 = 1.273, NS), with no correlation to baseline behavior on the rCET
(Figure 3d; adjusted r2 = 0.039, NS), although animals were still sensitive to the increasing
physical effort costs, overall (block: F3,75 = 4.607, p = 0.005).
EDT: Eticlopride administration
The dopamine D2 receptor antagonist eticlopride dose-dependently decreased all animals’ choice
of HR trials across all blocks (Figure 4a; dose: F3,63 = 0.038, p = 0.038; dose x group / dose x
block / dose x block x group: all Fs < 1.395, NS; saline vs high—dose: F1,21 = 3.900, p = 0.062;
saline vs low / saline vs med—dose: all Fs < 0.293, NS). Eticlopride also increased the time
needed to complete a HR choice, especially at the highest dose and for the highest effort (i.e.
FR20) block (dose: F3,30 = 3.296, NS; dose x block: F9,90 = 4.105, p = 0.039; dose x group / dose
x block x group: all Fs < 0.382; saline vs high—dose: F1,10 = 5.261, p = 0.045; saline vs low /
saline vs med—dose: all Fs < 2.178, NS; FR20 only—dose: F3,33 = 4.599, p = 0.033; FR2 / FR5 /
FR10 only—dose: all Fs < 3.024, NS). Eticlopride had no effect on the number of incomplete
HR responses (F3,63 = 2.067, NS) but modestly increased the number of choice omissions,
although choice omissions remained well below a single instance per animal per session even at
the highest dose (dose: F3,63 = 3.165, p = 0.030; saline vs low / saline vs med / saline vs high—
dose: all Fs < 3.424, NS).
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EDT: SCH23390 administration
The dopamine D1 receptor antagonist SCH23390 decreased choice of HR at the highest effort
block (Figure 4b; dose x block: F3,63 = 3.316, p = 0.009; FR20 only—dose: F3,63 = 5.165, p =
0.003; FR2 / FR5 / FR10 only—dose: all Fs < 1.783, NS; dose / dose x group / dose x block x
group: all Fs < 1.986, NS). SCH23390 also modestly increased the latency to complete HR trials
(dose: F3,39 = 3.773, p = 0.018; dose x group / dose x block / dose x block x group: all Fs <
1.935, NS). SCH23390 had no effect on incomplete HR responses (dose / dose x group: all Fs <
0.342, NS) but increased the number of choice omissions, again remaining below a single
instance per animal at the highest dose (dose: F3,63 = 3.275, p = 0.027; dose x group: F3,63 =
1.445, NS).
EDT: Yohimbine administration
The α2-adrenergic receptor antagonist yohimbine appeared to have some minor effects on choice
behavior, decreasing choice of the HR lever during the first two blocks, but this effect was not
robust, as evidenced by the lack of a dose x block effect (Figure 4c; dose: F3,60 = 2.506, p =
0.067; dose x group / dose x block / dose x block x group: all Fs < 1.641, NS; FR2 only—dose:
F3,60 = 3.570, p = 0.019; FR5 only—dose: F3,60 = 3.150, p = 0.031; FR10 / FR20 only—dose:
1.434, NS). Yohimbine also lengthened the latency to complete HR trials for each block (dose:
F3,39 = 9.147, p < 0.001; dose x block: F9,117 = 3.257, p = 0.001; FR2 only—dose: F3,48 = 4.219, p
= 0.010; FR5 only—dose: F3,48 = 9.496, p < 0.001; FR10 only—dose: F3,48 = 3.705, p = 0.018;
FR20 only—dose: F3,48 = 3.131, p = 0.034; dose x group / dose x block x group: all Fs < 1.567,
NS). Incomplete HR responses and choice omissions remained at zero for all animals at all
doses.
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EDT: Atomoxetine administration
The selective norepinephrine reuptake inhibitor atomoxetine had no effect on any behavioral
measures of the EDT (Figure 4d; dose / dose x group / dose x block / dose x block x group: all Fs
< 2.909, NS).
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