REPEATED POST- OR PRESESSION COCAINE ADMINISTRATION: ROLES OF DOSE AND FIXED-RATIO SCHEDULE

JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR
2004, 81, 169–188
NUMBER 2 (MARCH)
REPEATED POST- OR PRESESSION COCAINE ADMINISTRATION:
ROLES OF DOSE AND FIXED-RATIO SCHEDULE
JONATHAN W. PINKSTON AND MARC N. BRANCH
UNIVERSIT Y OF FLORIDA
Effects of repeated administration of cocaine to animals behaving under operant contingencies have
depended on when the drug is given. Moderate doses given presession have generally led to a
decrease in the drug’s effect, an outcome usually referred to as tolerance. When these same doses
have been given after sessions, the usual result has been no change or an increase in the drug’s
effects, with the latter usually referred to as sensitization. In the present study, repeated postsession
administration of a relatively small dose of cocaine (3.0 or 5.6 mg/kg) to pigeons responding under
a multiple ?xed-ratio 5, ?xed-ratio 100 schedule of food presentation generally resulted in tolerance
to the rate-decreasing effects of the drug. When the same dose was given before sessions, little
additional tolerance was observed, although some subjects showed further tolerance in the small-
ratio component. A regimen of repeated postsession injection of larger (10.0–23.0 mg/kg) doses
suppressed key pecking during the session; responding resumed following discontinuation of post-
session administrations. Effects of postsession administration of cocaine, therefore, depended on the
dose, with smaller doses leading to tolerance and larger ones to suppression of behavior during the
session. Effects of postsession drug administration of either small or large doses were not related to
whether effects of postsession drug were experienced mainly in the operant test chamber or in the
pigeon’s home cage. The results with large postsession doses are compatible with a view that the
drug acted as a Pavlovian unconditional stimulus, with the session-related stimuli acting as a long-
duration Pavlovian conditional stimulus. Tolerance following postsession administration of the small-
er doses challenges the view that it depended on experiencing the drug’s effects while the arranged
reinforcement contingencies were in effect.
Key words: cocaine, tolerance, contingent tolerance, Pavlovian conditioning, conditional-stimulus
duration, key peck, pigeons
Effects of repeated exposure to cocaine
work, one group of rats received ethanol be-
have varied. In some studies, effects of the
fore behavioral test sessions in a circular
drug have increased—a phenomenon gener-
maze, whereas another group received the
ally called sensitization (e.g., Downs & Eddy,
drug after each session. With his procedure,
1932a, 1932b; Post & Rose, 1976; Stewart &
sometimes called the Before-After, or B-A,
Badiani, 1993). In others, effects have de-
procedure, Chen found that tolerance to eth-
creased—an outcome usually labeled toler-
anol’s effects on maze performance devel-
ance (e.g., Mercier & Dessaigne, 1960; Moore
oped only in the rats that received the drug
& Thompson, 1978). Although the variables
before sessions, despite the fact that all rats
responsible for these two classes of outcomes
had received equivalent exposure to ethanol.
have not been fully delineated, it is clear that
Many subsequent experiments with the B-A
behavioral processes can play a role, both in
procedure, using both ethanol and other psy-
the development of sensitization (cf. Post,
choactive drugs, have shown a similar out-
Weiss, Fontana, & Pert, 1992) and of toler-
come: subjects receiving drugs before the test
ance (cf. Wolgin, 1989).
session become tolerant, whereas those re-
An important conceptualization of how be-
ceiving drug after sessions do not (Wolgin,
havioral factors can enter into the develop-
1989). Tolerance that depends on presession
ment of drug tolerance emanated from a line
drug administration is usually called ‘‘contin-
of research initiated by Chen (1968). In his
gent tolerance’’ (Carlton & Wolgin, 1971) to
contrast it with tolerance that results simply
Research supported by USPHS grants DA004074 and
from repeated drug exposure (sometimes
DA014249 from the National Institute on Drug Abuse.
called pharmacological tolerance).
The authors thank Margaret Gratton, Michelle Miller,
Woolverton, Kandel, and Schuster (1978)
and Jin Yoon for their assistance. Reprints may be ob-
were the ?rst to examine cocaine’s effects in
tained from the second author at Psychology Depart-
ment, Box 112250, University of Florida, Gainesville, Flor-
the B-A design, and they found that rats that
ida 32611 (e-mail: branch@u?.edu).
received cocaine repeatedly before daily ses-
169

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170
JONATHAN W. PINKSTON and MARC N. BRANCH
sions in which they drank milk became tol-
That is, as in Smith’s (1986) study, tolerance
erant to the drug’s intake-reducing effects
was more pronounced in the component with
whereas those that received an equivalent
the higher baseline rate of reinforcement.
regimen of postsession cocaine did not. Oth-
The present study extends these prior ?nd-
er investigations with rats (e.g., Smith, 1990)
ings with repeated cocaine administration un-
and also primates (e.g., Branch & Sizemore,
der multiple FR schedules in three ways. First,
1988) also have revealed contingent toler-
to assess the degree to which any tolerance
ance to effects of cocaine.
observed was an instance of contingent tol-
The most common account of contingent
erance, we compared effects of presession
tolerance is based on hypothesized behavioral
drug administration with postsession admin-
adjustments that develop during repeated
istration. Second, we examined the effects of
drug exposure (see Wolgin, 1989). In this
repeated administration of two different dos-
view, the drug produces novel patterns of be-
es of cocaine. Previous research with cocaine
havior that interact with the arranged rein-
has indicated that dose of drug given repeat-
forcement contingencies. Speci?cally, these
edly presession is an important determinant
interactions are presumed to result in the re-
of the outcome (e.g., Bowen, Fowler, & Kall-
inforcement of behavior that compensates for
man, 1993; Branch, Wilhelm, & Pinkston,
the drug-induced changes such that losses in
2000; Stafford & Branch, 1996.) Smaller dos-
reinforcement are counteracted (Schuster,
es often lead to tolerance, whereas larger dos-
Dockens, & Woods, 1966).
es frequently do not. In the present study, we
Research by Smith (1986) with amphet-
examined whether similar dose effects occur
amine revealed how behavioral parameters
when cocaine is repeatedly administered
can interact with repeated drug exposure. In
postsession. Third, the present experiments
his study, rats pressed a lever under a two-
were designed to examine the possibility that
component multiple schedule of food pre-
tolerance to cocaine’s effects on performance
sentation. One component was a differential-
maintained under multiple FR schedules
reinforcement-of-low-rate (DRL) schedule;
might also be in?uenced by Pavlovian factors.
the other was a random-ratio (RR) schedule.
Pavlovian conditioning has been implicated
Smith repeatedly administered a dose of am-
as a second type of behavioral process in-
phetamine that decreased RR rate and in-
volved in drug tolerance (e.g., Adams, Yeh,
creased DRL rate, thus reducing reinforce-
Woods, & Mitchell, 1969; Siegel, 1978). The
ment rate in both components. Tolerance
drug is conceptualized as an unconditional
developed in the RR component but not in
stimulus (US) that elicits unconditional re-
the DRL component. When he subsequently
sponses (UR). When drug is experienced re-
removed the RR component, tolerance ma-
peatedly in a particular context, that context
terialized in the DRL component. Smith not-
is posited to serve as a conditional stimulus
ed that baseline rate of reinforcement was
(CS) that elicits a conditional response (CR)
higher in the RR component, so he suggested
that is opposite of the UR, thus competing
that tolerance developed in the DRL com-
with the drug effect (for a review, see Siegel,
ponent only when it was isolated because
Baptista, Kim, McDonald, & Weise-Kelly,
gains in reinforcement rate afforded by tol-
2000). In an attempt to assess effects of pair-
erance in the DRL component were eclipsed
ing cocaine’s action with the test environ-
by those that occurred in the RR component
ment, postsession injections were followed ei-
when it was available.
ther by a return to the conditioning chamber
Similar differential tolerance development
for the duration of the peak action of the
to effects of cocaine has been reported by
drug or to the home cage.
Hoffman, Branch, and Sizemore (1987),
Hughes and Branch (1991), Nickel, Alling,
and Poling (1993), and van Haaren and An-
METHOD
derson (1994). In those experiments, multi-
Subjects
ple schedules with differently valued ?xed-ra-
tio (FR) schedules were employed, and
Eight experimentally naive White Carneau
tolerance development was generally limited
pigeons served. Each was maintained at ap-
to behavior controlled by smaller FR values.
proximately 80% of its free-feeding weight by

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PRE- OR POSTSESSION COCAINE
171
providing postsession feeding as necessary.
occurred. Autoshaping lasted from 5 to 12
Weights of individual pigeons are listed in Ta-
sessions across pigeons.
ble 1. Between sessions, subjects were housed
Next, sessions began with the key illumi-
individually in a temperature- and humidity-
nated red. Initially, each peck resulted in ac-
controlled colony room with a 16:8 hr light/
cess to grain. After four grain deliveries, the
dark cycle. Water and grit were continuously
ratio of pecks to food presentations was in-
available in the home cage.
creased to 2. Subsequently, the ratio was in-
creased to 4, 8, 11, 16, 20, 25, 30, 35, 40, 45,
Apparatus
50, 60, 70, 85, and 100. The criterion for in-
Two BRS/LVE pigeon chambers (Model
creasing the ratio was that every interre-
9381-D) were used. The inside dimensions of
sponse time in the ratio had to be less than
the chambers were 35 cm by 31 cm by 35 cm.
1 s for four consecutive ratios. Sessions ended
One wall held three horizontally aligned,
after 30 grain presentations, and the ratio at
translucent plastic response keys. The keys
the beginning of a session was the value
were 2.5 cm in diameter and centered 8 cm
achieved at the end of the preceding session.
from the ceiling. Only the center key was
For Pigeon 91, the sequence of ratios was
used, and it could be transilluminated by 1.1-
modi?ed after FR 70 because of relatively low
W lamps that provided white, red, or green
and erratic rates of responding at larger ra-
illumination. Each peck with a force of at
tios. For this pigeon, the ?nal ratio was FR
least 0.15 N was counted as a response and
75.
produced 30-ms operation of a Mallory Son-
The ?nal schedule arrangement was then
alert (2900 Hz tone). A 1.1-W lamp (house-
introduced. It consisted of a multiple FR 100
light) 2 cm from the top center of the wall
FR 5 schedule. Each session began with the
provided general illumination. A 6 cm by 4
key illuminated red (FR 100 component; FR
cm opening was located 8.5 cm below the
75 for Pigeon 91). After four grain presenta-
center key, and mixed grain could be made
tions, a 30-s intercomponent interval with all
available through it via operation of a sole-
lights out was presented. The key then was lit
noid-operated feeder. During each 3-s feeder
green (FR 5 component) for the next four
operation the aperture was illuminated by a
grain presentations, after which the intercom-
1.1-W lamp, and all other lights in the cham-
ponent interval ensued. This continued until
ber were extinguished. To mask extraneous
each component had occurred three times.
sounds, white noise at 95 dB was present in
To ensure exposure to both components of
the room in which the chambers resided. Pro-
the multiple schedule when response rates
gramming and recording of experimental
were low, time limits were in effect in each
events were accomplished by a computer sys-
component. They were 25 min for the FR-100
tem (Palya & Walter, 1993).
component and 5 min for the FR-5 compo-
nent. If the time limit expired, the intercom-
Procedure
ponent interval commenced automatically.
Training and baseline conditions. Throughout
Once daily response rates were considered
the study, sessions were conducted 7 days per
stable (i.e., showed no systematic session-to-
week at about the same time of day for each
session variation over at least a 10-session
subject. Sessions were preceded by a 5-min
span, as judged by visual inspection), an ad-
blackout in which no stimuli were presented
ditional 30 sessions were conducted before
and no contingencies were arranged. Key
drug testing began. The total number of ses-
pecking was established using an autoshaping
sions of exposure to the ?nal multiple sched-
(cf. Brown & Jenkins, 1968) procedure. Pre-
ule before drug testing began ranged from
sentations of grain, each preceded by 8-s il-
45 to 65 across pigeons.
lumination of the key by white light, occurred
Drugs and injection procedures. Cocaine hy-
on a variable-time 60-s schedule. Sessions last-
drochloride, obtained from the National In-
ed for 50 food presentations. The ?rst peck
stitute on Drug Abuse, was dissolved in 0.9%
to the lighted key resulted in immediate pre-
sodium chloride solution, which served as the
sentation of grain. The key was then contin-
vehicle. Doses were determined as the salt,
uously illuminated, and each peck produced
and injections were made into the breast
immediate access to food until 50 pecks had
muscle in a volume of 1.0 ml/kg. When two

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172
JONATHAN W. PINKSTON and MARC N. BRANCH
Table 1
Conditions and numbers of sessions for each pigeon.
Pigeon
Order
33(464g)
521(519g)
32(470g)
586(488g)
1
*Large (5.6)a Post(C)b - 116c *Small (5.6) Post(H) - 130 *Small (5.6) Post(C) - 158 *Small (5.6) Post(H) - 162
2
Saline(C) - 55
*Small (5.6) Pre(H) - 152
Large (10) Post(C) - 77
*Small (5.6) Pre(H) - 207
3
Large (5.6) Post(H) - 55
Saline(C) - 116
Saline(C) - 60
Saline(H) - 18
4
Saline(H) - 80
Large (10) Post(C) - 50
Large (10) Post(H) - 25
Large(23) Post(H) - 30
5
Saline(C) - 15
Saline(C) - 20
Saline(H) - 28
Saline(H) - 28
6
Large (5.6) Post(C) - 25
Large (10) Post(H) - 120
Large (10) Post(H) - 38
Saline(C) - 10
7
Saline(C) - 30
Saline(H) - 25
*Saline(H) - 148
Large(23) Post(C) - 55
8
Saline(H) - 30
Saline(C) - 38
Saline(C) - 15
Saline(C) - 38
9
Large (5.6) Post(H) - 35
Large (10) Post(C) - 44
*Small (5.6) Pre(C) - 164
10
*Saline(H) - 113
Saline(C) - 15
11
*Saline (3) Post(C) - 137
12
*Small (3) Pre(C) - 152
a Dose in mg/kg.
b Postsession condition; C
Chamber, H
Home cage.
c Number of sessions in the condition.
* Dose-response effects assessed.
injections per day were scheduled, the ?rst
effect curves was designed to allow evaluation
alternated daily between the left and right
of their stability. Giving doses in two succes-
breast; the second was into the opposing
sive ?xed sequences and then retesting some
breast. When testing presession drug admin-
doses permitted observation of any systematic
istration, cocaine injections occurred imme-
changes over the 10 to 21 weeks (i.e., 70 to
diately before placing pigeons in the experi-
147 sessions) needed to complete determi-
mental chamber. When testing postsession
nation of effects. No such trends were ob-
drug administration, injections occurred ap-
served for any subject.
proximately 20 min after session termination.
Repeated drug-administration procedures.
Immediately after each session, pigeons were
Three dosing conditions were studied in as-
placed for 20 min in a wire-mesh holding
sessing the effects of repeated cocaine admin-
cage that was situated in a room adjacent to
istrations: (a) ‘‘small’’ drug dose repeatedly
that in which sessions were conducted. All
administered postsession, (b) small drug dose
postsession injections occurred at the end of
repeatedly administered presession, and (c)
the 20-min period. After the injection, a pi-
‘‘large’’ drug dose repeatedly administered
geon was either returned to its home cage
postsession. Different pigeons experienced
(home-cage condition) and fed if needed, or
the three conditions in different orders. A
it was returned to the conditioning chamber
condition continued until day-to-day perfor-
for 40 min (chamber condition). During this
mance was considered stable for 10 or more
time, the chamber’s houselight was illuminat-
sessions.
ed, but the key was not, and pecks had no
When a small dose of cocaine was given
scheduled consequences. At the end of the
postsession, 4 pigeons were studied in the
40 min, the houselight was extinguished, and
home-cage condition and 3 in the chamber
the pigeon was returned to its home cage and
condition. Each session was preceded by a sa-
fed if needed.
line injection and followed by an injection of
Dose-effect determinations. Various doses of
cocaine (at the end of the 20-min holding
cocaine were administered before sessions
period). Designation of the dose as small in-
once per week. The doses initially examined
dicated that it did not substantially suppress
were 0 (Saline), 10.0, 5.6, 3.0, and 1.0 mg/
behavior when administered acutely, and
kg, in that order. The sequence was then re-
more importantly, did not result in elimina-
peated. After these determinations, these and
tion of pecking when it was given repeatedly
other doses were sometimes tested in an ir-
postsession. Table 1 shows where in the order
regular order. This method of assessing dose-
of experimentation this condition occurred

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PRE- OR POSTSESSION COCAINE
173
Table 1
(Extended)
Pigeon
562(334g)
393(431g)
91(483g)
57(454g)
*Small (5.6) Post(H) - 184
Large (10) Post(C) - 95
*Large (10) Post(C) - 95
*Small (5.6) Post(H) - 138
*Small (5.6) Pre(H) - 215
Saline(C) - 40
Saline(C) - 105
Small (5.6) Pre(H) - 8
Saline (H) - 60
Saline (H) - 52
Large (17) Post(H) - 25
Large (10) Post(H) - 36
Saline(H) - 35
Saline(H) - 53
Saline(C) - 16
*Saline(C) - 30
Large (17) Post(C) - 44
*Small (5.6) Post(C) - 181
Saline(C) - 20
*Small (5.6) Pre(C) - 170
for each pigeon, the number of sessions in
sample of performance under the chronic
each condition, and whether the animal was
dose. That is why in Table 2, for the small-
returned to its home cage or to the chamber
before conditions, the listed numbers of ‘‘ob-
after each session.
servations’’ are relatively large for one of the
When pigeons received the relatively small
doses for each pigeon. That dose was the
dose before each session, 3 were tested in the
chronic dose. Similarly, in calculating a mean
home-cage condition and 3 in the chamber
value for sessions preceded by injections of
condition. Saline was given at the end of the
saline in the small-after conditions, we used
20-min holding period. For each pigeon, the
data from sessions that occurred the day be-
same dose that had been identi?ed previously
fore tests with doses of cocaine. That is why
as small for examination of postsession effects
the listings in Table 2 of numbers of obser-
was given before each session. Pigeon 57 be-
vations of effects following saline (dose of 0)
came ill after 8 days of exposure to presession
are relatively large in the small-after condi-
cocaine and was removed from the study.
tions.
Dose-response functions were reassessed
When an injection of a relatively large dose
once exposure to pre- or postsession admin-
of cocaine followed each session (at the end
istration of the smaller dose had led to stable
of the 20-min holding period), an injection
session-to-session performance. This was ac-
of saline preceded each session. Large doses
complished by substituting a presession injec-
were initially identi?ed as the smallest that
tion of cocaine for the daily dose once per
acutely decreased substantially or eliminated
week. Tests with additional doses did not be-
pecking during the session. An exception was
gin until at least 60 sessions of daily admin-
Pigeon 586. For this subject, 23 mg/kg was
istration had passed and performance was
?nally selected as the large dose after tests
judged stable. The same method of determin-
with 10 and 17 mg/kg failed to produce re-
ing the dose-response function that had been
sults consistent with those of the remaining
used to assess acute effects was employed.
subjects. Doses eventually classi?ed as large
The numbers of times each dose was tested
typically resulted in the suppression of peck-
in each condition are shown in Table 2. To
ing when administered repeatedly postsession
calculate mean values for effects of the re-
(see results). That is, they were classi?ed as
peatedly administered (chronic) dose when a
large based on the outcome of experiments
small dose was given before every session, in-
with postsession dosing.
stead of taking data from all the sessions pre-
Following every case in which a large dose
ceded by this dose, we used the data from
was administered after sessions, the next
sessions that occurred the day before tests
phase consisted of administering saline in
with other doses or with saline. We judged
both daily injections. As noted in Table 1, 6
that these sessions provided a representative
of the 8 subjects were exposed to both the

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174
JONATHAN W. PINKSTON and MARC N. BRANCH
Table 2
Number of observations for each dose during dose-effect assessments.
Dose (mg/kg)
Pigeon
Condition
0
1.0
3.0
5.6
10
17
23
30
32
Acute
4
3
3
3
3
—
—
—
Small-After
12
2
2
3
3
2
—
—
Salinea
10
2
2
2
2
2
—
—
Small-Before
2
2
2
12
3
3
—
—
33
Acute
4
2
2
2
2
—
—
—
Large-After
9
2
2
2
3
—
—
—
Saline
8
2
2
2
2
—
—
—
Small-After
8
2
2
2
2
—
—
—
Small-Before
3
2
13
2
6
—
—
—
57
Acute
4
3
3
2
2
—
—
—
Small-After
11
2
3
2
2
2
—
—
91
Acute
2
2
3
5
4
—
—
—
Large-After
4
1
1
1
1
—
—
—
393
Acute
4
2
2
2
4
2
—
2
Large-After
5
1
1
1
1
1
—
—
Saline
14
2
2
3
2
3
—
2
Small-After
2
3
2
3
2
2
—
—
Small-Before
4
2
2
16
3
2
—
2
521
Acute
4
2
2
3
4
—
—
—
Small-After
11
2
3
2
2
2
—
—
Small-Before
2
2
2
13
2
5
—
—
562
Acute
2
2
2
2
2
2
—
—
Small-After
18
2
2
2
4
4
4
—
Small-Before
3
3
2
21
2
6
5
—
586
Acute
2
3
3
3
3
3
—
—
Small-After
14
2
3
2
3
2
2
—
Small-Before
2
2
2
14
2
2
4
—
a Saline vehicle administered both before and after sessions.
home-cage and chamber conditions during
Effects of Relatively Smaller Doses
repeated administration of a large dose.
Administered Postsession
Dose-response functions often were not as-
Although small doses were de?ned in part
sessed during repeated postsession testing
by the fact that they did not eliminate key
with a large dose. As reported below, these
pecking when given repeatedly after sessions,
conditions generally led to a cessation of key
they did alter responding in some pigeons.
pecking. Hence we assumed that if no peck-
Figure 1 shows data from the ?rst and last 10
ing followed the presession administration of
sessions of exposure to repeated postsession
saline that regularly occurred in the condi-
administration of a small dose. Response-rate
tion, tests with other, nonzero, doses would
decreases of about 40 to 60% in the FR 100
show the same thing. That supposition was
component occurred for Pigeons 32, 57, and
con?rmed in the three cases (Pigeons 33, 91,
521, and rate was lowered occasionally in the
393) in which dose-response functions were
FR 5 component for 586. These effects were
determined during repeated postsession ad-
not systematically related to whether the peak
ministration of a large dose.
action of the drug occurred in the operant-
conditioning chamber or in the home cage.
Figure 2 reveals that repeated postsession
RESULTS
administration of a smaller dose generally re-
Because order of exposure played no dis-
sulted in tolerance. Six of the 7 pigeons
cernible role in the main effects, the data are
showed clear shifts to the right in dose-re-
organized and presented by the three major
sponse functions. In 5 of those 6 pigeons,
repeated-dosing conditions.
curves were shifted to the right in both com-

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PRE- OR POSTSESSION COCAINE
175
Fig. 1.
Response rates over the ?rst ten sessions and last ten sessions of the conditions in which a small dose of
cocaine was given after each session. Graphs on the left are from the chamber condition; graphs on the right are
from the home-cage condition. Pigeon identi?cation numbers (and dose) are shown on each graph. Filled circles
show data from the FR 100 component of the multiple schedule; open squares are from the FR 5 component.
Unconnected symbols at the left show mean data (with ranges) from the last ?ve sessions before postsession drug
administration began.
ponents of the multiple schedule. In 586, the
der FR 100 might more accurately be char-
shift was evident only in the FR 100 compo-
acterized as ?attened, but doses that origi-
nent, but the only dose at which tolerance
nally eliminated pecking no longer did so—
could have been seen for responding under
an outcome consistent with those seen in the
FR 5 was the largest, 23 mg/kg, and no
other subjects. The overall picture is that tol-
changes in effect of this dose were evident.
erance, which was generally independent of
For Pigeon 33, the function for behavior un-
schedule parameter, resulted from repeated

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176
JONATHAN W. PINKSTON and MARC N. BRANCH
Fig. 2.
Response rate as a function of dose of cocaine. Points are means of all administrations of each dose, and
bars indicate ranges. If no bar is visible, the point covers the range. The points above C show means and ranges from
all sessions that immediately preceded acute injections; those above S show means and ranges following administration
of the saline vehicle before sessions that immediately preceded tests with presession doses of cocaine. Each row shows
data for 1 pigeon, with that pigeon’s identi?cation number appearing between the graphs. Data in the left column
are from the FR 100 component of the multiple schedule; those on the right are from the FR 5. Filled circles show
effects of acute administrations, whereas open squares show effects after repeated exposure to postsession adminis-
tration of a small dose of the drug. Next to each pigeon identi?cation number is the dose given repeatedly. The
letter in parentheses indicates whether the pigeon was returned to its home cage (H) or to the conditioning chamber
(C) after receiving the drug. The functions for acute effects in Pigeons 33 and 393 are from a second assessment
(see text).

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PRE- OR POSTSESSION COCAINE
177
exposure to postsession administration of the
presession administration of cocaine resulted
doses selected.
in additional tolerance that depended on the
For 2 pigeons, 33 and 393, examinations of
reinforcement schedule parameter. Also wor-
effects of small postsession doses came after
thy of note is the effect of the repeatedly ad-
those with larger doses. Before testing with
ministered dose on behavior under the FR 5
smaller doses, therefore, baseline perfor-
schedule. The effects depicted in Figure 3 are
mance was reestablished in these 2 subjects,
representative of performance throughout
and dose-response determinations were con-
the repeated-administration phase. That is,
ducted to ascertain if the prior experience
the dose was essentially without effect on per-
with large doses had altered the functions.
formance. Nevertheless, additional tolerance
Because the dose-response functions had
was observed in some pigeons.
shifted slightly to the right, that is, modest
tolerance was evident (data not shown), the
Effects of Relatively Large Doses
new ‘‘acute’’ curves were used in subsequent
Administered Postsession
comparisons for these 2 pigeons. For the re-
When the dose given postsession was rela-
maining 5 pigeons exposed to this condition,
tively large, the eventual result in most cases
effects of small doses were examined ?rst, so
was that key pecking during the session was
their original acute dose-response cur ves
eliminated in both components of the mul-
served as the basis of comparisons.
tiple schedule. In a minority of cases, pecking
was not eliminated, but its rate was reduced.
Effects of Relatively Smaller Doses
These effects are illustrated in Figure 4,
Administered Presession
which shows rates from 10-session blocks. The
Five pigeons were exposed to this condi-
blocks were selected to show periods of major
tion immediately after completion of assess-
transition in pecking rates. For example, the
ment of effects of postsession administration
two graphs at the top of the ?gure show data
of the small dose. A 6th subject, Pigeon 32,
from Pigeon 32. The left graph illustrates the
did not experience the condition until after
transition from baseline levels of responding
intervening exposure to three different post-
to nearly complete suppression in the home-
session regimens with a large dose. Conse-
cage condition. Key pecking ceased com-
quently, its dose-response function was rede-
pletely by the 18th session in the ?rst expo-
termined before assessment of effects of
sure to this condition (?lled circles, open
presession administration of a small dose.
squares), and by the 13th session in the sec-
The redetermination revealed little systemat-
ond exposure (data not shown). In both ex-
ic change from the curve generated during
posures, rates in the large ratio decreased to
repeated exposure to the small dose postses-
zero before those in the small ratio. Follow-
sion (compare the open squares for this sub-
ing removal of postsession cocaine, respond-
ject in Figures 2 and 3). Nevertheless, the
ing recovered to baseline levels.
more recent function was used in the com-
Similar results were obtained with Pigeon
parisons, which are summarized for all 6 pi-
32 in the chamber condition, as shown in the
geons in Figure 3. The graphs in the left col-
graph on the right. Postsession drug admin-
umn reveal that curves for effects in the
istration eventually resulted in complete sup-
FR-100 component were not systematically al-
pression of key pecking and, as before, large-
tered. For Pigeon 562, baseline rates during
ratio performance decreased sooner than
FR 100 fell during this condition, but the
small-ratio responding. Also similar was the
form of the dose-response curve was gener-
recovery of performance once the drug ve-
ally unaffected. The functions in the right
hicle was substituted for cocaine.
column, however, do show a change in several
The results for Pigeon 32 are generally
subjects. Under the FR 5 schedule, 3 pigeons,
characteristic of those of the other pigeons.
33, 393, and 521, showed clear shifts in the
Three exceptions are notable, however. First,
functions indicative of tolerance. Speci?cally,
for Pigeon 521, key pecking was reduced, but
rate decreases produced by large doses were
never completely eliminated, as a result of
attenuated. Pigeon 586 also showed a small
postsession administration of 10 mg/kg. The
effect in this component suggestive of toler-
reduction was greater when drug administra-
ance. In these subjects, therefore, repeated
tion was followed by a return to the condi-

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178
JONATHAN W. PINKSTON and MARC N. BRANCH
Fig. 3.
Response rate as a function of dose of cocaine. Filled triangles show data following a period of repeated
exposure to presession administration of a small dose of cocaine. Open squares are the data resulting after a period
of repeated postsession administration of the same dose (i.e., they are the same data as the open squares in Figure
2, except for Pigeon 32; see text). Other details are as in Figure 2.

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