INFLUENCES ON COCAINE TOLERANCE ASSESSED UNDER A MULTIPLE CONJUNCTIVE SCHEDULE OF REINFORCEMENT

JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR
2009, 92, 413–422
NUMBER 3 (NOVEMBER)
INFLUENCES ON COCAINE TOLERANCE ASSESSED UNDER A MULTIPLE CONJUNCTIVE
SCHEDULE OF REINFORCEMENT
JIN HO YOON
BAYLOR COLLEGE OF MEDICINE
AND
MARC N. BRANCH
UNIVERSITY OF FLORIDA, GAINESVILLE
Under multiple schedules of reinforcement, previous research has generally observed tolerance to the
rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of
fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement.
The current experiment examined the effects of cocaine on key-pecking responses of White Carneau
pigeons maintained under a three-component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5
responses) schedule of food presentation. Dose-effect curves representing the effects of presession
cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic
administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine
generally resulted in tolerance to the response-rate decreasing effects of cocaine, and that tolerance was
generally independent of relative FI value, as measured by changes in ED50 values. Daily administration
of saline decreased ED50 values to those observed when cocaine was administered acutely. The results
show that adding a FR requirement to FI schedules is not sufficient to produce schedule-parameter-
specific tolerance. Tolerance to cocaine was generally independent of FI-parameter under the present
conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be
dependent on FI parameter.
Key words: cocaine, tolerance, fixed-interval schedule, fixed-ratio schedule, conjunctive schedule,
multiple schedule, key peck, pigeons
_______________________________________________________________________________
Tolerance is defined as an attenuation of a
cocaine on rates of responding maintained
drug’s effects most often following repeated or
by fixed-ratio (FR) schedules. Pigeons were
prolonged exposure, requiring higher doses to
exposed to a three-component multiple FR
recapture the original drug effect (Corfield-
schedule of reinforcement in which the FR
Sumner & Stolerman, 1978; Hardman, Gil-
values ranged from 5 to 125. Chronic (i.e.,
man, & Limbird, 1995; Wolgin, 1989). Toler-
once daily) administration of cocaine pro-
ance is typically reflected in a rightward shift in
duced tolerance to the initial decreases in
the drug’s dose-effect curve.
response rates under small- and intermediate
Although the definition is silent with regard
FR values, whereas little or no tolerance to the
to mechanisms of tolerance, behavioral factors
effects of cocaine was observed under large FR
can mediate tolerance development (Demell-
values. This effect of relative FR value has been
week & Goudie, 1983; Siegel, 1989; Wolgin,
reliably demonstrated in studies examining
1989). For instance, Hoffman, Branch, and
cocaine’s effects in the context of multiple FR
Sizemore (1987) examined the effects of
schedules with both pigeons (Nickel, Alling,
Kleiner, & Poling, 1993; Pinkston & Branch,
We thank the following people for assistance in
2004a; Yoon & Branch, 2004), rats (van
conducting the research project: Peg Gratton, Jon
Haaren & Anderson, 1994), and squirrel
Pinkston, Michelle Miller, Julie Marusich, and Stacey
monkeys (e.g., Hughes & Branch, 1991).
McFeron. This research was supported in part by research
grants F31 DA 015975, RO1 DA 004074, and K05 DA
In contrast to the findings noted above,
014249 from the National Institutes of Health.
Schama and Branch (1989) exposed pigeons
Address correspondence to J. H. Yoon, Ph. D., Baylor
to a multiple fixed-interval (FI) schedule of
College of Medicine, Veterans Affairs Building #110, Mail
reinforcement in which the three different FI
Stop BCM 350, Houston, TX 77030; ph: (717) 791-1414,
ext. 4153 (e-mail: jiny@bcm.edu).
values (i.e., 5 s, 30 s, and 120 s) were chosen to
doi: 10.1901/jeab.2009.92-413
approximate the baseline interreinforcement
413

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414
JIN HO YOON AND MARC N. BRANCH
times observed in the Hoffman et al. (1987)
after the lapse of the FI, if the FR has already
study. As in the Hoffman et al. experiment,
been completed (cf. Barrett, 1974, 1975, 1976;
dose-related decreases in response rates were
Herrnstein & Morse, 1958). In the present
observed following acute administration of
study, an FR 5 was employed to determine if
cocaine. Unlike the Hoffman et al. study,
the presence of a relatively small ratio require-
however, tolerance to cocaine’s rate-decreas-
ment would interact with the FI to alter the
ing effects was similar across components
development of tolerance. The current exper-
following chronic administration of cocaine.
iment therefore extends the analysis initiated
In other words, tolerance was independent of
by Pinkston and Branch (2004b) to a proce-
schedule parameter, as well as the consequent
dure that allows the ratio requirement to be
different reinforcement rates.
completed at any time within the interval.
As differences in baseline reinforcer rates
were not sufficient for producing parameter-
specific tolerance, an alternative interpreta-
METHOD
tion of the disparate results may lie in the
Subjects
number of responses required to obtain
Six experimentally na?¨ve White Carneau
reinforcement. Under an FR schedule, the
pigeons, maintained at 80% of their free-
number of responses required to obtain
feeding weight, served as subjects. They were
reinforcement is simply the FR value. Under
individually housed in a temperature-con-
an FI schedule, however, only one response is
trolled colony room with a 16:8 hr light:dark
required to obtain reinforcement. If rates are
cycle. Pigeons had continuous access to water
very low following drug administration, a
and health grit in their home cages and were
single reinforced response may enhance sub-
provided supplemental food following sessions
sequent responding. The added presence of a
as needed to maintain them at 80% of their
small FR requirement to the FI schedule
free-feeding weights. Treatment of the animals
eliminates this feature. For example, Pinkston
was approved by the local Institutional Animal
and Branch (2004b) exposed pigeons to a
Care and Use Committee.
three-component multiple FI schedule of
reinforcement in which the FI values were
Apparatus
similar to those used in the current study.
Additionally, each FI component had a tan-
Sessions were conducted in a BRS/LVEH
dem FR 5 requirement. Under tandem sched-
operant conditioning chamber for pigeons,
ules, a reinforcer is delivered when two or
with interior dimensions 31 cm wide by 35 cm
more schedule requirements, with the same
high and 35 cm deep. Except for the front
stimulus conditions, are completed in se-
wall, the walls and ceiling were painted white.
quence (Catania, 1998; Ferster & Skinner,
The chamber floor was composed of steel
1957). In the study by Pinkston and Branch,
mesh. The front wall, made of brushed
chronic administration of presession cocaine
aluminum, was equipped with three response
resulted in comparable tolerance to the rate-
keys, a house-light, and food aperture. The
decreasing effects across components.
response keys were 2.5 cm in diameter and
In the Pinkston and Branch (2004b) study,
horizontally aligned 24 cm above the chamber
reinforcement was always delivered contingent
floor. Only the center key was used in the
on completion of the FR requirement. An
current experiment. The response key could
alternative method of adding an FR require-
be transilluminated by 1.1-W, 28-VDC lamps
ment to an interval schedule is to use a
and required a static force of approximately
conjunctive
schedule.
Under
conjunctive
0.18 N, which resulted in a 30-ms tone
schedules, two or more schedule requirements
(2900 Hz) via a Mallory SonalertTM. The house
must all be completed for reinforcement to be
light was a 1.1-W, 28-VDC lamp that was
delivered, however, their order of completion
centered 2.5 cm below the top of the panel.
does not matter (Catania, 1998; Herrnstein &
An aluminum shield deflected the lamp’s light
Morse, 1958). Under a conjunctive FI FR
toward the ceiling. The food aperture was
schedule, therefore, reinforcement is deliv-
5.8 cm by 6 cm and centered 10 cm from the
ered on completion of the FR, if finished after
chamber floor. When mixed grain was avail-
the lapse of the FI, or on the first response
able, all other chamber lights were extin-

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COCAINE TOLERANCE AND CONJUNCTIVE SCHEDULES
415
guished, and the food aperture was illuminat-
initiated. Typically, the FI values began at 1 s
ed by a 1.1-W, 28-VDC lamp. A MEDH
and were increased across sessions. Subjects
Associates Single Channel I/R Source, Detec-
649, 893, and 612 were exposed to a multiple
tor, and Control generated and sensed an
FI 1-s FI 1-s FI-s (two sessions), multiple FI 10-s
infrared beam across the opening of the food
FI 10-s FI 10-s (t sessions), multiple FI 10-s FI
aperture. Entries and exits into and out of the
30-s FI 30-s, and finally a multiple FI 10-s FI 30-
food aperture were detected by breaks in the
s FI 120-s schedule, with the three FI values
photo-beam. White masking noise of approx-
correlated with the red, green, and white key
imately 95 dB was continuously present in the
lights, respectively. For subjects 439, 27, and
room where the chamber resided. A ventila-
4970, the FI value associated with the white key
tion fan on the back chamber wall provided
was introduced at 120 s, rather than 1 s.
additional masking noise. Programming and
Baseline. Each component lasted for four
recording of experimental events was accom-
food presentations or until a time limit had
plished via a dedicated computer system
elapsed. The time limits for the 10-s, 30-s, and
(Palya, Walter, & Chu, 1995). A GerbrandsTM
120-s FI components were 1.5 min, 4 min, and
Model C-3 cumulative recorder also provided a
10 min, respectively. Components were pre-
real-time record of responding.
sented randomly, without repetition within a
block. Sessions consisted of three blocks.
Procedure
Maximum
session
length
was
therefore
Sessions were conducted 7 days per week at
46.5 min.
approximately the same time each day. Each
Once behavior under the terminal FI values
session was preceded by a 5-min blackout
was established, all components were changed
during which the chamber was dark and no
to a conjunctive FI FR schedule; the FI values
consequences were programmed for respond-
remained the same and the FR value was 5 for
ing. Sessions were initiated with illumination
all components. If five or more responses were
of the house and key lights.
made during the FI, then the first response
Initial training. Subjects reliably ate from the
after the lapse of the interval resulted in food
food aperture following one session of train-
presentation. If fewer than five responses were
ing. Subjects 439, 27, and 4970 were subse-
made during the interval, then the fifth
quently trained to emit key-peck responses on
response resulted in presentation of food.
the white key under an FI 120-s schedule of
Baseline was considered stable once response
reinforcement. Responding failed to general-
rate, pausing, and cumulative-record response
ize when the other two components were
patterns were judged to be so by visual
introduced with corresponding other key
inspection (161 to 201 sessions).
colors. These subjects were retrained along
Drug preparation and administration procedures.
with the rest of the subjects using the following
Cocaine hydrochloride, provided by the Na-
procedure. Subjects were trained to respond
tional Institute on Drug Abuse, was dissolved
on the transilluminated response key by
in 0.9% saline, which served as the vehicle.
reinforcing a series of responses that succes-
Intramuscular injections into the breast mus-
sively approximated pecking (Ferster & Skin-
cle occurred immediately prior to a session.
ner, 1957). Appropriate responses produced 3-
When injections occurred daily, the site
s access to grain. The color of the response key
alternated between the left and right breast
alternated among white, green, and red
in order to minimize potential for tissue
following every reinforcer delivery. Once
trauma. Drug volume was 1.0 ml/kg, and
responding reliably occurred with each key
doses are reported as mg of the salt form per
color (one to two sessions) a three-component
kg body weight of the subject.
multiple FI schedule was introduced. The first
Acute effects of cocaine. During the Acute
response occurring after the interval lapsed
Phase, various doses of cocaine were adminis-
resulted in 2-s access to food. The timer that
tered immediately before sessions, usually
controlled food access started when the
once per week. These probe injections were
pigeon inserted its head into the food aper-
separated by at least 5 days. Initially, saline,
ture. If the pigeon did not initiate feeding
10.0, 5.6, 3.0, and 1.0 mg/kg of cocaine were
within 5 s of food presentation, the hopper
administered in that order, and then the
was lowered and timing of the next FI was
sequence was repeated in order to permit

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416
JIN HO YOON AND MARC N. BRANCH
Table 1
Average rates of key-pecking (6SEM) from control and saline sessions from the Acute, Chronic,
and Saline Phases.
Subject
FI
Acute Phase Control
Acute Phase Saline
Chronic Phase Saline
Saline Phase Saline
649
10 s
131.4(0.4)
131.4(7.3)
119.7(2.1)
113.3(0.9)
30 s
71.0(0.8)
87.9(3.0)
80.2(3.6)
80.1(0.8)
120 s
29.7(0.2)
33.6(0.7)
27.0(3.0)
35.1(0.5)
4970
10 s
100(0.7)
109.5(3.8)
103.7(5.2)
105.6(0.6)
30 s
79.9(0.5)
77.9(4.0)
67.3(1.2)
81.2(0.4)
120 s
68.8(0.4)
67.7(1.0)
62.4(2.7)
70.0(0.5)
893
10 s
94.9(0.7)
89.0(5.8)
91.5(6.6)
94.3(1.2)
30 s
62.2(0.3)
62.7(1.4)
55.1(0.8)
47.5(0.6)
120 s
68.1(0.5)
59.7(1.8)
57.4(5.5)
57.1(0.3)
612
10 s
126.0(0.4)
134.9(0.9)
79.0(7.8)
120.9(0.4)
30 s
85.9(0.4)
88.6(1.5)
34.2(2.5)
61.6(0.6)
120 s
36.4(0.2)
30.0(0.6)
17.9(1.0)
35.7(0.3)
27
10 s
181.6(0.3)
181.9(1.4)
169.3(2.8)
175.9(0.3)
30 s
89.4(0.6)
89.4(0.6)
94.5(2.8)
83.5(0.7)
120 s
64.0(0.4)
63.6(4.6)
73.1(3.8)
60.3(0.8)
439
10 s
105.3(0.5)
102.6(2.2)
96.5(6.4)
128.1(1.2)
30 s
73.3(0.4)
75.5(3.5)
69.2(9.4)
80.0(0.5)
120 s
38.0(0.3)
36.0(1.6)
36.5(2.5)
38.0(0.4)
assessment of the stability of the dose–
visual inspection. Next, probe sessions were
response function. Further administrations of
conducted during the Saline Phase. Each
these doses or others were investigated on an
probe dose examined was assessed at least
individual-subject basis in order to provide a
twice, and further determinations were made
complete characterization of the dose–re-
as needed for each subject. Sessions conduct-
sponse function and its stability.
ed the day before probe sessions were used to
Chronic effects of cocaine. Based on the dose–
represent the effects of saline.
response functions generated during the
Data analysis. The curve-fitting program
Acute Phase, a dose of cocaine was chosen
GraphPad PrismE was used to calculate the
for each subject that reduced rates of respond-
estimated dose at which responding was
ing without completely suppressing them. This
decreased to 50% of baseline (ED50; Ross &
dose was administered daily during the Chron-
Kenakin, 2001). First, response rates were
ic Phase for at least 50 consecutive sessions and
normalized as a proportion of rates observed
until stability in daily response rates was
during saline-administration sessions for each
observed, as judged by visual inspection of
component during each phase (Table 1).
daily response rates and cumulative records.
Second, data points were fitted to a four-
Next, probe doses were administered in the
parameter sigmoidal model. The four param-
context of chronic cocaine administration.
eters consisted of the ED50 value, the slope of
Any doses that had been examined during
the function, and the bottom and top of the
the Acute Phase were administered at least
curve. In fitting the model, the bottom and top
twice, and further doses were administered on
of the curves were initially constrained to 0%
an individual-subject basis in order to provide
and 100%, respectively. Calculated ED50
a complete characterization of the dose–
values are listed in Table 3. In a small number
response function and its stability. Data from
of cases (3/54), the model would not converge
sessions conducted the day before probe
under these conditions. For these cases, the
sessions were used to represent the effects of
top constraint was removed, and the model
the chronic dose. The Chronic Phase was
converged. As a validity check, all ED50 values
completed within 110 to 206 sessions.
were reassessed without constraining the top
Repeated saline administrations. After the
of the model. By and large, differences in
Chronic Phase, administration of daily preses-
ED50 values were relatively minimal when the
sion cocaine was replaced by that of saline for
top of the model was constrained to 100% and
at least 50 sessions and until stability in daily
when it was not. In one final case, the model
response rates was observed, as judged by
would not converge as the dose–response

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COCAINE TOLERANCE AND CONJUNCTIVE SCHEDULES
417
Fig. 1.
Key-pecking rates as a function of cocaine dose during the Acute and Chronic Phases. Data for each subject
are presented horizontally while components are presented vertically. Circles and squares represent mean rates at each
dose during the Acute and Chronic Phases, respectively. Rates as a proportion of those observed during saline sessions
are shown on the ordinate. Dose of cocaine is represented on the abscissa on a log scale. Error bars represent 6SEM.
Errors bars that are not visible are subsumed by the data point. Note that ordinate extends to 1.5 for each plot except for
Subjects 649 and 612 in the FI 120-s component, which extends to 1.75.

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418
JIN HO YOON AND MARC N. BRANCH
Table 2
Obtained ED50 values and comparison of ED50 values from various phases.
Acute vs. Chronic p Acute vs. Saline p
Acute
Chronic
Saline
value
value
649
FI 10 s
5.3
11.1
6.3
,.0001
.3400
FI 30 s
6.0
10.7*
6.7
,.0001
.3978
FI 120 s
5.5**
11.5**
5.4
,.0001
..9999
4970
FI 10 s
7.6
10.3
8.9
.0020
.0680
FI 30 s
7.8
10.6
7.9
.0006
.8714
FI 120 s
5.3
6.7
5.6
.0209
.6129
893
FI 10 s
3.0
7.3
4.0
.0002
.1655
FI 30 s
4.5
5.8
5.3
.4144
.5197
FI 120 s
3.2
5.6
4.1
.0034
.1813
612
FI 10 s
3.6
7.4
3.6
,.0001
.9635
FI 30 s
3.3
7.4
3.3
,.0001
.6473
FI 120 s
3.7
5.6
3.5
,.0001
.6525
27
FI 10 s
4.4
3.8
2.3
.4829
.0026
FI 30 s
4.5
4.2
3.5
.5943
.0793
FI 120 s
3.7
2.7
1.7
.0867
,.0001
439
FI 10 s
4.5
6.9
5.7
.0279
.2764
FI 30 s
6.1
6.5*
6.4
.9977
.8099
FI 120 s
5.8
4.2
6.1*
.0059
.8345
Average
4.9
7.1
5.0
Note. Global nonlinear regression was used to compare ED50 values.
* ED50 value obtained with top of the model unbound.
** ED50 value obtained shifting response rate values by the difference from obtained saline values.
function was bimodal (Figure 1, 649, FI 120 s).
were little affected by 1.0 and 3.0 mg/kg of
For this individual instance, data were trans-
cocaine and were either at 0 or near 0 rates at
formed to fit the model by shifting the curve
10.0 mg/kg of cocaine at all components for
downwards at doses in which the average rate
all subjects. Rates of responding observed
of responding was higher than that of the
during saline-administration sessions during
average rates observed during saline sessions.
the Acute Phase closely matched those ob-
First, the average saline rate was subtracted
served during control sessions. Response rates
from the average rate for a given dose. This
were generally highest in the FI-10 s compo-
difference was then subtracted from each
nent across subjects and tended to decreases as
individual data point for a given dose. This
a function of FI value.
effectively reduced the rate at each dose until
Repeated daily administration of cocaine
it was equivalent with that observed during
(Chronic Phase) generally resulted in toler-
saline sessions while preserving the variability
ance as shown by rightward shifts in dose–
observed at each dose.
response functions and significant increases in
All ED50 comparisons were done using
ED50, and that tolerance was generally inde-
global nonlinear regression analyses (Motulsky
pendent of FI value (Figure 1; Table 2).
& Christopoulous, 2003). The analyses com-
Significant increases in ED50 values were
pared whether the data from two dose–
observed in 5 out 6 subjects in at least one of
response functions were better described by
the components. Overall, significant increases
one (shared ED50 value) or two curves (two
in ED50 values were observed in 66.7% (12/
separate ED50 values). The null hypothesis was
18) of the components and those increases
that the data would be better described by one
averaged 1.8-fold (SEM 6 0.03; Table 3). Only
curve and the alpha level was set to p , .05.
subject 27’s data failed to show tolerance in
any of the components. For this subject, ED50
values obtained during the Chronic Phase
RESULTS
were lower in all three components relative
Dose-related decreases in key-pecking were
to the Acute Phase (Table 2), but these
observed during the Acute Phase (Figure 1,
decreases were not significant. A significant
filled symbols). Generally, rates of responding
decrease in the ED50 value (Table 2), mir-

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COCAINE TOLERANCE AND CONJUNCTIVE SCHEDULES
419
Table 3
during the Chronic Phase and in most cases
Mean percentage of reinforcers (6SEM) delivered on
recaptured those observed during the Acute
completion of the FR requirement for each component in
Phase (Table 2). The only increased ED50
sessions preceding probe-injection sessions during the
value was observed in the FI 120 s component
Chronic Phase.
for subject 439. Note that this subject was the
Subject
FI 10 s
FI 30 s
FI 120 s
only one to show a significant decrease in
ED50 value for that component during the
649
0.0(0.0)
0.0(0.0)
2.8(0.3)
4970
3.1(0.5)
7.3(0.4)
3.1(0.3)
Chronic Phase. Comparison of normalized
893
10.4(1.6)
1.3(0.4)
10.0(1.1)
dose–response functions from the Acute Phase
612
12.5(1.7)
16.4(1.1)
13.5(1.0)
and Saline Phase showed only significant
27
1.6(0.3)
8.3(0.6)
16.8(1.4)
decreases in ED50 values for subject 27 in
439
1.4(0.5)
0.0(0.0)
31.8(1.9)
the FI 10-s and 120-s components (Table 2).
rored by a leftward shift in the dose–response
function (Figure 1), from the Acute to the
DISCUSSION
Chronic Phase was observed for subject 439 in
The purpose of the current experiment was
the FI 120-s component. Only subject 439’s
to examine the effects of cocaine on respond-
data showed clear evidence of tolerance
ing under conjunctive FI FR schedules of
related to FI value with significant increases
reinforcement. The major findings were that
in ED50 values in the FI 10-s and 30-s
(1) almost all subjects exhibited some degree
components and a significant decrease in the
of tolerance to the response-rate-decreasing
ED50 in the FI 120-s component (Table 2).
effects of cocaine following repeated adminis-
During the Chronic Phase, the vast majority
tration of presession cocaine, (2) the degree of
of reinforcers were delivered on completion of
tolerance observed was generally independent
the FI schedule requirement (Table 3). In other
of FI parameter size, and (3) when repeated
words, most of the reinforcers were delivered
administration of cocaine was replaced by that
following more than five responses before
of saline, dose–response functions from the
completion of the FI schedule requirement.
Acute Phases were generally recaptured.
Note, as a point of comparison, only one
The overall pattern of tolerance observed in
reinforcer (i.e., Subject 439 in the FI 10-s
the current experiment is comparable to that
component) was delivered on completion of
observed
in
studies
utilizing
comparable
the FR requirement in the six sessions preced-
schedule parameters from our laboratory
ing the Chronic Phase (data not shown). The
(Hoffman et al., 1987; Pinkston & Branch,
percentage of FR-delivered reinforcers (i.e., five
2004a; Pinkston & Branch, 2004b; Schama &
or fewer reinforcers) was generally similar across
Branch, 1989; Weaver & Branch, 2008; Yoon &
components for any given subject in the
Branch 2004) and other laboratories as well
Chronic Phase. Two exceptions to this general
(Nickel et al., 1993; van Haaren & Anderson,
pattern were Subjects 27 and 439. Subject 27
1994). Thus, the current experiment adds to
received an increasing percentage of FR-deliv-
the increasing body of work showing tolerance
ered reinforcers that paralleled increases in the
to the disruptive effects of cocaine on re-
FI interval length. Subject 439 received relatively
sponding by pigeons under multiple schedules
more FR-delivered reinforcers in the FI 120-s
of reinforcement.
component relative to the other two compo-
The effects of daily cocaine administration
nents. Comparing across subjects, the percent-
were generally similar across components and
age of FR-delivered reinforcers for 439 was
therefore congruent with other studies using
approximately 2 to 11 times greater than any
similar multiple FI schedules of reinforcement
other subject in the FI 120-s component.
(Schama & Branch, 1989; Pinkston & Branch,
Once daily administration of presession
2004b). The combined results of the current
cocaine was replaced with that of saline vehicle
experiment and those of Pinkston and Branch
(Saline Phase), dose–response functions gen-
(2004b) suggest that the mere presence of an
erally shifted to the left and often mirrored
FR requirement is not sufficient for consis-
those observed during the Acute Phase (Fig-
tently developing schedule-parameter-specific
ure 2). Likewise, ED50 values almost univer-
tolerance. In contrast to the above studies,
sally decreased (17/18) from those observed
Weaver and Branch (2008) observed parame-

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420
JIN HO YOON AND MARC N. BRANCH
Fig. 2.
Key-pecking rates as a function of cocaine dose during the Acute and Saline Phases. Triangles represent mean
rates at each dose during the Saline Phase. All other details are as in Figure 1.
ter-specific tolerance using a response-initiat-
ment. The results of that study suggested that
ed, multiple-FI (FI 5 s, FI 15 s, & FI 60 s)
delay to reinforcement from the initial re-
schedule of reinforcement, or a multiple FI
sponse may play a role in the manifestation of
schedule with an initial tandem FR1 require-
parameter-specific tolerance.

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COCAINE TOLERANCE AND CONJUNCTIVE SCHEDULES
421
Related to the above discussion, Subject 439
although see Stafford, Branch, & Hughes,
was the one exception that showed parameter-
1994 for an exception).
specific tolerance in the current experiment
Overall, the current study showed that
(Figure 1). One way in which Subject 439’s
tolerance to cocaine was generally indepen-
experience differed from the other pigeons
dent of FI parameter even when a small ratio
was the relatively high percentage of FR-
requirement was added. The presence of a
delivered reinforcers in the FI 120-s compo-
ratio requirement per se, therefore, was not
nent (Table 3). Despite the findings noted in
reliably sufficient to make tolerance depen-
the Weaver and Branch (2008) study noted
dent on the FI parameter.
above, we find it unlikely that the delay
between the first response in an interval and
food delivery was responsible for the develop-
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Received: March 29, 2007
115–180). Clifton, NJ: Humana Press.
Final Acceptance: July 15, 2009

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