Psychopharmacology(1991) 103:121-128

Psychopharmacology
Springer-Verlag 199t

Situational specificity of tolerance to effects

of phencyclidine on responding of rats under fixed-ratio
and spaced-responding schedules*
James B. Smith
Worcester Foundation for Experimental Biology,222 Maple Avenue, Shrewsbury,MA 01545, USA
Received December 18, 1989 / Final version May 29, 1990

Abstract. Responding of rats (n = 5) was maintained under DRL (lever) and Time-Delay (nose-key) schedules of
food presentation in different experimental chambers
during two separate daily sessions. Tolerance that developed to rate-decreasing effects of phencyclidine for
nose-key pressing under the Time-Delay schedule did not
extend to effects of phencyclidine on lever pressing under
the DRL schedule. In a second experiment, both lever
and nose-key pressing of rats were maintained under
individual and multiple fixed-ratio schedules. One group
of animals (n = 5) experienced both the individual and the
multiple schedules in the same experimental chamber and
another group (n = 5) experienced the individual and the
multiple schedules in different experimental chambers.
Tolerance that developed to behavioral effects of phencyclidine during the individual schedule did not extend to
responding on even the same manipulandum under the
multiple schedule in a different experimental chamber. In
contrast, tolerance that developed to behavioral effects
of phencyclidine during the individual schedule did extend to responding on even the different manipulandum
under the multiple schedule in the same experimental
chamber. Thus, tolerance that developed in the environment that was coincident with the pharmacologic actions
of phencyclidine did not extend to similar operants in a
different environmental condition, but did extend even to
a different operant and schedule context in the same
environmental condition.

Key words: Phencyclidine - Behavioral tolerance - DRL

- Time-Delay - FR - Rat
*Animals used in this study were maintained in accordance with
guidelinesof the AnimalCare Committeeof the WorcesterFoundation for ExperimentalBiologyand of the "Guide for Care and Use
of Laboratory Animals" of the Institute of Laboratory Animal
Resources, National Research Council, Department of Health,
Education and Welfare, Publication Number (NIH)85- 23, revised
1985

A number of experiments have demonstrated behavioral

influences on drug tolerance by comparing effects of
drugs when they are initially administered after, and the
before, daily experimental sessions (Siegel 1976; Murray
et al. 1977; Smith 1979; Post et al. 1981). Since pharmacologic effects of post-session drug administration do not
typically coincide with behavioral processes associated
with experimental procedures, any tolerance that develops during such drug administration cannot involve
behavioral processes that occur during the experimental
sessions. And conversely, when tolerance to behavioral
effects of a drug does not develop during post-session
drug administration, but then does develop during subsequent pre-session drug dosing, that tolerance probably
does involve behavioral processes associated with the
environmental situation and procedures occurring
during the session.
Two general kinds of behavioral processes are often
considered to influence tolerance to the behavioral effects
of drugs. For one, behavioral effects of a chronically
administered drug are considered to be influenced by the
extent to which initial effects of the drug interfere with
normal relations between the behavior and its consequences, and there has recently been considerable discussion of ways in which "reinforcer loss" and "compensatory behavior" may influence tolerance to behavioral
effects of many drugs (e.g., Balster 1985; Barrett et al.
1989; Blackman 1989; Wolgin 1989). In the other behavioral influence on tolerance, discriminable physiological
effects of a drug are considered to become associated
with environmental stimuli which are coincidental with
drug administration, without regard to specific behavioral consequences. Several experiments have shown that
external situational stimuli develop control over physiological responses of certain drugs (Kayan et al. 1973;
Siegel 1975, 1978, 1982, 1989; Siegel and Sdao-Jarvie,
1986), and tolerance is considered to result from this
associative, or Pavlovian, conditioning.

122
Experiments studying influences on tolerance of reinforcer loss and compensatory operant behavior have not
systematically studied the joint influence o f associative
processes, and experiments studying influences of Pavlovian associative processes have not systematically studied compensatory operant responding (but see Smith
1979; Sannerud and Young 1986). However, the experience o f reinforcer loss invariably occurs in the
presence of specific environmental circumstances, and
the occurrence of associative conditioning is usually in
the midst of instrumental activity, so that the two
processes will typically occur simultaneously.
Recent experiments in this laboratory have studied
associative influences on drug tolerance using a multienvironment procedure in which the same subjects are
studied in different sets of operant circumstances at different times each day. With this procedure, a drug that
is administered before a second or third daily session also
occurs after earlier sessions during the same day. This
permits measurement o f behavioral effects during concurrent before/after drug administration in the same subject and provides a way to systematically study the associative and discriminative influence of identifiable environmental features on tolerance generalization. In a
previous experiment, for example, tolerance that developed to the behavioral effects of cocaine in one environment did not extend to operants maintained under
either a different schedule or with a different manipulandum when those different operants occurred in a different
environmental situation (Smith 1990b). Additionally,
tolerance that developed to the behavioral effects of
morphine in one environment did not extend to an operant maintained under even the same schedule and with
the same manipulandum when that operant occurred in
a different environmental situation (Smith 1990a). This
absence of tolerance generalization for cocaine, morphine, and the cannabinoid l-nantradol is similar to that
reported previously for tolerance to effects of phencyclidine (Woolverton and Balster 1979) and LSD (Murray
et al. 1977) on schedule-controlled behavior of rat, and
for tolerance to effects of ethanol on cognitive behavior
of humans (Shapiro and Nathan 1986). In contrast, however, there are also reports that tolerance does generalize
for effects o f physostigmine (Genovese et aI. 1988) and
phencyclidine (Murray 1978) on schedule-controlled behavior of rats, and for tolerance to the effects of ethanol
on m o t o r coordination and maze performance o f the rat
(Leblanc et al. 1975).
Phencyclidine has pronounced behavioral and discriminative effects (Balster 1987) which diminish with repeated administration (Beardsley and Balster 1988).
Moreover, phencyclidine is recognized as a widely and
illicitly used drug for which tolerance may increase its
frequency or dosage in further use. Consequently, it will
be helpful to more fully characterize the influence of
behavioral processes on tolerance to the behavioral
effects o f this drug.
The present experiment studied associative influences
on tolerance development to behavioral effects o f
phencyclidine using a multi-environment procedure. In
experiment 1, lever and nose-key pressing o f rats were

maintained under different spaced-responding schedules

of food delivery in different environments. The purpose
of this experiment was to study tolerance generalization
for responding with different manipulanda, in different
environmental circumstances, and under different
schedules o f food presentation, but involving a putatively
similar behavioral process o f timing. In experiment 2,
lever and nose-key pressing of rats were maintained under the same fixed-ratio schedule of food delivery in
either an individual or a multiple schedule in either the
same or different environments. The purpose of this
experiment was to study tolerance generalization for
responding in different behavioral contexts, but with the
same individual schedule of reinforcement, and in either
the same or different environmental situation.
In experiment 1, tolerance that developed to behavioral effects of phencyclidine on spaced responding with
a nose-key in the environment coincident with the
pharmacologic actions o f the drug did not extend to
spaced responding with a lever in a different environmental situation. In experiment 2, tolerance that developed to effects o f phencyclidine on F R responding
during an individual schedule extended to F R responding during a multiple schedule when the individual and
the multiple schedules occurred in the same, but not
when they occurred in different, environmental situations.

Materials and methods

Subjects" and apparatus

Fifteen experimentally naive male Charles River CD aIbino rats
(F344) were maintained at 300 g body weight and were approximately 6 months old at the start of the experiment. Experiments
were conducted with individual rats placed in one of two Model
C Rat Cages (23 cm long x 20 cm wide x 20 cm high; Gerbrands
Corp., Arlington, Mass.) or in a smaller clear lucite chamber measuring 25 cm long x 15 cm wide x 15 cm high. Each Model C Cage
contained a response lever (G6312, Gerbrands) centered on a short
wall of the chamber and mounted 7.5 cm up from the grid floor;
a response key (G6315, Gerbrands) mounted in the lower right
corner of the same wall; a recessed food cup (F7020, Gerbrands)
mounted in the lower left comer of the same wall, and a water bottle
and speaker on the opposite walt. The food cup was connected to
a solenoid-operated pellet dispenser (G5100, Gerbrands). One of
the Model C cages had standard clear lucite walls and the other
Model C cage had walls that were darkened with black construction
paper. The smaller clear lucite chamber contained a response lever
(G6312, Gerbrands) mounted on one of the 15 cm walls in the lower
right corner; a food cup (F7020, Gerbrands) mounted on the same
wall in the lower left corner; and a speaker and a water tube on the
opposite wall. Sessions in all cages were accompanied by masking
noise and a 7-W light mounted either directly over the lever or
behind the nose-key. All chambers were enclosed in larger sound
attenuating boxes. The control and recording of all scheduled
events used an IBM AT-compatible computer with BehaviorPlus TM
software developed by Princeton Economics, Inc. (Princeton,
Mass.).

Experiment 1
Behavioral procedure. Lever and nose-key pressing were trained by
selectivelyreinforcing desired features of behavior, and responding

123
was initially maintained under a one-response fixed-ratio schedule
which delivered single food pellets (0.045 g, Noyes) in the presence
of a white keylight in the darkened Model C chamber (nose-key
pressing) or a white light over the lever in the clear Model C
chamber (lever pressing). Lever pressing was subsequently maintained in daily sessions at 8:00 a.m. in the clear chamber under a
schedule in which each response had to be preceded by 30 s of no
responding in order for one food pellet to be delivered (DifferentialReinforcement-of-Low Rate; DRL). Food could only follow a
response terminating a minimum interval, and intervening responses reset the interval. Nose-key pressing was subsequently
maintained in daily sessions at 1:00 p.m. in the darkened chamber
under a schedule in which each response had to be followed by 30 s
of no responding in order for one food pellet to be delivered (TimeDelay, Dews 1960). Food could only follow a response initiating a
minimum interval, and intervening responses reset the interval.
Thus, food occurred after a pause and then a response under the
DRL schedule, but after a response and then a pause under the
Time-Delay schedule. Animals responded under these conditions
until variability of response rate for each schedule was within
20% for 2 successive weeks.

Drug procedure. Phencyclidine hydrochloride (phencyclidine HC1;

provided by the National Institute on Drug Abuse, Rockville,
Maryland) was dissolved in a 0.9% sodium chloride solution and
injected IM in a volume of 0.5 ml/kg body weight. Similar volumes
of vehicle served as control injections. After initial training, each
animal received at least five injections of each of several doses of
phencyclidine (0.3-3.0 mg/kg) once weekly in mixed order immediately prior to each experimental session. Phencyclidine has a
rapid onset of action and the immediate pre-injection permitted
observation of initial behavioral effects. When animals received
phencyclidineprior to the first session, they were not studied on that
day in the second session, Each animal also received at least seven
injections of vehicle once weekly immediately prior to each experimental session, and the average of these sessions was used for
comparing pre-drug control responding with effects of both acutely
and chronically administered phencyclidine.
After determination of acute dose effects, animals received
3.0 mg/kg/day phencyclidine for 4 weeks at each of the following
times: after Time-Delay responding in the second daily session;
before Time-Delay responding in the second session; before DRL
responding in the first daily session; and then once again before
Time-Delay responding in the second session. During the final
4 weeks, animals also received occasional probe injections of
phencyclidine before DRL responding in session 1.

Experiment 2
Behavioral procedure. Lever and nose-key pressing were trained by
selectively reinforcing desired features of behavior, and responding
was initially maintained under a one-response fixed-ratio schedule
which delivered single food pellets (0.045 g, Noyes). With the clear
lucite Model C chamber, lever pressing of experimental animals
(n = 5) was maintained in the presence of a clicking noise and a white
light mounted over the lever, and nose-key pressing was maintained
in the presence of a tone noise and a white light mounted behind
the nose-key (multiple schedule). After initial training, the response
requirement was gradually increased to 30, and schedule components alternated every 20 reinforcers or 10 rain, whichever occurred first. Daily sessions at 7:00 a.m. lasted for three exposures
of each component (approximately 60 min). With the smaller clear
lucite chamber, lever pressing of the same animals was maintained
in the presence of a clicking noise and a white light mounted over
the lever (individual schedule). After initial training, the response
requirement was gradually increased to 30, and daily sessions at
1:00 p.m. lasted for 60 min. Animals responded under these conditions until variability of response rate for each schedule was
within 20% lbr 2 successive weeks. This procedure is depicted in
Fig. 1.

_1_
Environment

FR30 (Lev)
F R 3 0 (Key)
0 7 0 0 hrs
C

_ _ ~.

(Lev)
1 3 0 0 hrs

FR30

Phencyclidine

Administration

Fig. 1. Depiction of the multi-environment procedure for experiment 2. Lever and nose-key pressing were separately maintained
under a multiple FR30 schedule during the first daily session in one
chamber, and lever pressing was maintained under an individual
FR30 schedule during the second daily session. Some animals
(n = 5) experienced both sessions in the same experimental chamber,
and other animals (n = 5) experienced each session in different experimental chambers. Phencyclidine was administered at times A,
B, or C during the course of the experiment. Effects of chronic
administration at times B and C correspond to effects shown in
panels B and C of Figs. 3 and 4
Control animals (n = 5) responded under the same schedule and
manipulanda conditions twice daily in the same clear lucite Model
C chamber. Lever pressing and nose-key pressing were maintained
at 9:00 a.m. under a multiple schedule, and lever pressing was
maintained at 3:00 p.m. under an individual schedule.

Drug procedure. Acute administration of phencyclidine was the

same as in experiment 1. Drug was dissolved in a 0.9% sodium
chloride solution and injected IM in a volume of 0.5 ml/kg body
weight. Similar volumes of vehicle served as control injections.
After initial training and development of stable performance, each
animal received at least five injections of each of several doses of
phencyclidine (0.3-3.0 mg/kg) once weekly in mixed order immediately prior to each experimental session. When animals
received phencyclidineprior to the first session (Fig. 1, condition C),
they were not studied on that day in the second session (Fig. 1,
condition B). Each animal also received at least seven injections of
vehicle once weekly immediately prior to each experimental session,
and the average of these sessions was used for comparing pre-drug
control responding with effects of both acutely and chronically
administered phencyclidine.
After determination of acute dose-effects using the same
general procedure described for experiment 1, animals received
3.0 mg/kg/day phencyclidine for 4 weeks at each of the following
times: after the individual schedule in the second session (Fig. 1,
Condition A); before the individual schedule in the second session
(Fig. 1, condition B); and then before the multiple schedule in the
first session (Fig. 1, condition C).

Resuhs

Experiment 1
Control responding. Behavior was readily c o n t r o l l e d u n der b o t h D R L a n d T i m e - D e l a y schedules i n separate
e x p e r i m e n t a l c h a m b e r s , a n d rates a n d p a t t e r n s o f b o t h
r e s p o n d i n g a n d food delivery were c o m p a r a b l e to those
c o m m o n l y r e p o r t e d for similar schedules a n d p a r a m e t e r s
presented i n d i v i d u a l l y (Smith 1986; H i l t u n e n et al. 1989).
Lever pressing u n d e r the D R L schedule o c c u r r e d at

124
P h e n e y e l i d i n e (3 m g / k g / d a y )
A

B
Before Time-Delay
Second Session

Acute

Administration

~3

DRL

Spaced-Responding

Before DRL
First Session

Before Time-Delay
Second Session

T/~

~2

P,

0.3

1.0 1.7

s.o

10

15

Blocks of Two
(mg/kg}
Fig. 2. Effectsof acute (Panel A) and repeated daily administration
(PaneLs B-D) of phencyclidine on responses/m (+ 1 SD) under
Time-Delay (filled circles; control X = 2.01 :k 0.09) and DRL (open
circles; control X = 1.36:t:0.23) schedules. Phencyclidine (3,0 rag/
kg) was administered after responding of both sessions (not shown);
before Time-Delay responding of the second session (Panel B);
before DRL responding of the first session (panel C); and before
Time-Delay responding of the second session (panel D). During
drug administration shown in panel D, phencyclidinewas administered twice before the first session(marked by an asterisk). Response

Dose

1.92-2.11 responses per min and there were generally

75-88 reinforcers per session. Nose-key pressing under
the Time-Delay schedule occurred at 0.76-1.37 responses
per rain and there were generally 63-82 reinforcers per
session.

Acute drug effects. Lever pressing under the D R L

schedule was increased, and the frequency of food delivery was decreased, as the dose of phencyclidine increased
to 3.0 mg/kg (Fig. 2A, open circles). In contrast, nosekey pressing under the Time-Delay schedule was only
decreased as the dose of phencyclidine increased to
3.0 mg/kg (Fig. 2A, filled circles).
Chronic dru9 effects. Responding was not affected for
either schedule when 3.0 mg/kg/day phencyclidine was
administered for 4 weeks after the second daily session
(not shown in Fig. 2). When phencyclidine was then
given before Time-Delay responding in the second daily
session, responding was decreased just as it had been
when phencyclidine was given acutely (Fig. 2B, filled
circles). Consequently, pharmacologic effects of 3.0 rag/
kg/day phencyclidine for 4 weeks after both sessions had
not resulted in significant tolerance to its behavioral
effects on Time-Delay performance. As phencyclidine
continued to be administered before Time-Delay responding, however, tolerance developed to decreased responding within 2 weeks (Fig. 2B, filled circles).
There were no effects on D R L responding in the first
daily session throughout the period of phencyclidine
injections prior to Time-Delay responding in the second
daily session (Fig. 2B, open circles). Then, when phency-

20

25

30

Sessions

rate was compared for selected sessions of each panel, and t-tests
for dependent-samples verified visual inspection. Time-delay responding during session 1 (filled circles panel B) was the same as
for acutely administered 3 mg/kg [t(4)=0.319]; DRL responding
during session 11 (open circles, panel C) was the same as for acutely
administered 3 mg/kg [t(4)= 1.37]; and DRL responding during
sessions 24 and 29 (open circles marked by asterisks, panel D) was
higher than DRL responding during sessions 23 and 2 respectively
[t(4)=3.15, P<0.025 one-tailed and t(4)=12.66, P<0.01 onetailed]
clidine was given immediately before D R L responding,
that behavior was increased to approximately the same
extent as when drug had been given acutely (Fig. 2C,
open circles). This increased D R L responding occurred
after 8 weeks of daily phencyclidine administration and
clearly suggests that tolerance did not generalize significantly to behavioral effects on D R L responding while
phencyclidine was experienced outside circumstances
associated with D R L performance. As phencyclidine
continued to be administered before D R L responding,
however, tolerance developed to increased responding
within approximately 2 weeks (Fig, 2C, open circles).
After tolerance had developed to increased D R L
responding in the first daily session, phencyclidine was
once again administered daily before Time-Delay responding in the second session for 4 weeks. There was no
disruption of D R L or Time-Delay responding associated
with this change in dosing time (Fig. 2D, first three data
points). Then, when drug was occasionally administered
before D R L responding in probe sessions, that responding approximately doubled (Fig. 2D, at asterisks). This
suggests that tolerance to the behavioral effects of
phencyclidine on D R L responding was partly "lost"
when the pharmacologic activity of drug again occurred
outside the behavioral circumstances associated with
D R L performance.

Experiment 2
Control responding. Behavior was readily controlled under the FR30 schedule in both the individual and the

125

Different Environment

Phencyclidine (3 mg/kg/day)
A
1.25

44

B
Before
Individual Schedule

Acute
Administration

Before
Multiple Schedule

1.00
0.75

0
CO

0.50

g
t'r"

0.25

p '-~ ,~i,,. I
0.3

"~
1.0

1.7

3,0

Dose (mg/kg)

1.25

20

Blocks of T w o Sessions

(panel B); and before responding on both manipulanda during the

morning session with the multiple schedule (panel C). Response rate
was compared for selected sessions of each panel, and t-tests for
dependent-samples verified visual inspection. Responding on both
manipulanda during session 11 of the multiple schedule (squares,
panel C) was no different than that after acutely administered
3 mg/kg phencyclidine [t(4)=0.064 nose-key; t(4)=0.206 lever].
Lever responding during session 11 of the individual schedule (open
circles, panel C) was no different than during vehicle control conditions [t(4)= 1.24]

Fig. 3. Effects of acute (panel A) and repeated daily administration

(panel B and C) of phencyclidine on responses/s ( t SD) under an
FR30 schedule of lbod presentation. Squares are for a multiple
schedule at 7: 00 a.m, with nose-key pressing (filled points; control
X=0.890.12) and lever pressing (open points; control
X=0.650.08), The open circle is for an individual schedule of
lever pressing in a different experimental enviroment at 1 : 00 p.m.
(control ~=0.81 0.09). Phencyclidine (3.0 mg/kg) was administered after responding of both sessions (not shown); before lever
responding during the afternoon session with an individual schedule

Phencyclidine

15

10

Same

(3 m g / k g / d a y )

Environment

Acute
Administration

Before
Individual Schedule

Before
Multiple Schedule

a
co 1.oo
44
"1o

o 0.75
0
D
Cq

u~

0.50
I Key Mult

0
c~

DoLev Molt
Lev lndiv

O,25

0.3

1.0

1.7

3.0

Dose (rng/kg)

10

15

20

Blocks of TWO Sessions

Fig. 4. Effects of acute (panel A) and repeated daily administration

(panets B and C) of phencyclidine on responses/s ( 1 SD) under
an FR30 schedule of food presentation. Squares are for a multiple
schedule at 9:00 a.m. with nose-key pressing (filled points; control
R = 0.96 :t: 0.10) and lever pressing (open points; control X = 0.82
0,11). The open circle is for an individual schedule of lever pressing
in the same experimental environment at 3:00 p.m. (control
R = 0.74 :t: 0.09). Phencyclidine (3.0 mg/kg) was administered after
responding of both sessions (not shown); before lever responding
during the afternoon session with an individual schedule (panel B);

and before responding on both manipulanda during the morning

session with the multiple schedule (panel C). Response rate was
compared for selected sessions of each panel, and t-tests for dependent-samples verified visual inspection. Responding on both manipulanda during session 11 of the multiple schedule (squares, panel
C) was greater than that after acutely administered 3 mg/kg phencyclidine It(4)= 15.25 nose-key; t(4)= 8.47 lever], although it was less
than that during session 10 (panel B) when animals last received
phencyclidine after multiple-schedule sessions It(4) = 11.8 nose-key;
t(4) = 3.54 lever]

126
multiple schedules. Lever pressing during the individual
schedule occurred at 0.66-0.84 responses per second and
animals received 75-100 reinforcers per session. Lever
pressing during the multiple schedule occurred at
0.57-0.88 responses per second and animals received
32-56 reinforcers per session in that component. Nosekey pressing during the multiple schedule occurred at
0.78-1.15 responses per second and animals received
44-67 reinforcers per session in that component.

Acute drug effects. FR responding on both manipulanda

was decreased as dose of phencyclidine increased for
individual and multiple schedules occurring in both different (Fig. 3A), and the same environmental circumstances (Fig. 4A).
Chronic drug effects. Responding was not affected for
either schedule when 3.0 mg/kg/day phencyclidine was
administered for 4 weeks after the second daily session
(Fig. 1, Condition A; data not shown in Figs. 3 and 4).
When phencyclidine was then given before FR lever responding in the second daily session (Fig. 1, condition B),
that responding was initially decreased just as it had been
when phencyclidine was given acutely (Figs. 3B and 4B,
open circles). As phencyclidine continued to be administered before lever responding of the individual schedule,
however, tolerance developed to increased responding
within approximately 4 weeks. Consequently, pharmacologic effects of 3.0 mg/kg/day phencyclidine for 4
weeks after both sessions did not result in significant
tolerance to its behavioral effects on FR lever performance, but marked tolerance did develop when drug
administration preceded that performance.
There were no effects on FR responding in the multiple schedule during the first daily session for either group
throughout the period of phencyclidine injections prior
to the second daily session with the individual schedule
(Figs. 3B and 4B, squares). However, there were markedly different effects for the two groups when phencyclidine
was given immediately before FR responding in the multiple schedule (Fig. 1, condition C). For experimental
animals experiencing the individual and multiple
schedules in different environmental circumstances, FR
responding on both manipulanda of the multiple
schedule were markedly decreased when phencyclidine
first preceded multiple schedule responding (Fig. 3C,
squares). This indicates that tolerance which had developed for other behavioral effects of phencyclidine
during 8 weeks of drug administration for these animals
did not generalize significantly to their effects on FR
responding in the multiple schedule. In contrast, initial
effects of phencyclidine on responding in the multiple
schedule were not as great for control animals experiencing both individual and multiple schedules in the same
environment (Fig. 4C, squares). This indicates that
tolerance which had developed for other behavioral
effects of phencyclidine during 8 weeks of drug administration for these animals did partially generalize to
their FR responding in the multiple schedule. Thus,
characteristics of the environmental apparatus were corn-

paratively more influential on tolerance generalization

than were differences for schedule context or manipulanda.
Discussion

Responding was readily controlled and maintained in

two different environmental situations by spacedresponding (experiment 1) and fixed-ratio (experiment 2)
schedules of food presentation, and rates and patterns of
performance were comparable to those commonly reported for similar schedules and parameters when
presented individually. These effects on DRL responding
are similar to those reported previously for rats' lever
pressing under DRL schedules of food delivery (Poling
et al. 1981 ; Sanger and Jackson 1989) and mice responding under a DRL schedule of sweetened milk presentation (Balster and Baird 1979). The present results are the
first we are aware of for rate-decreasing effects of phencyclidine on spaced-responding maintained under a TimeDelay schedule, and they suggest that contingencies of
reinforcement for the two schedules are more influential
on the behavioral effects of phencyclidine than a putatively common "timing process".
Responding under the FR schedule was decreased as
dose of phencyclidine increased to 3.0 mg/kg. These
effects are similar to those reported previously for rats
(Poling et al. 1981; Beardsley and Balster 1987), and
squirrel monkeys (Chait and Balster 1978) responding
under an FR schedule of food presentation and for mice
responding under an FR schedule of milk delivery (Wenger and Dews 1976). Segal et al. (1981) reported increased FR lever pressing by phencyclidine in rats, but
inspection of their cumulative records suggests that their
observed increase in FR responding may have resulted
from elimination of post-food pausing instead of increased responding per se.
When animals in the present experiment received
daily injections of 3.0 mg/kg phencyclidine, tolerance to
behavioral effects of drug developed only in the presence
of environmental stimuli that were coincident with
pharmacologic effects of the drug. Tolerance did not
develop to behavioral effects on responding under any
schedule studied when injections occurred after the last
daily session and therefore outside all behavior
procedures. These effects of post-session drug administration have been previously reported for a number
of drugs and schedule-conditions, and they support the
general conclusion that tolerance to unspecified behavioral effects occurring outside observed experimental
conditions does not necessarily generalize to performance characteristics measured under experimental circumstances (Siegel 1976; Murray et al. 1977; Smith
1979; Woolverton and Balster 1979). In addition, however, the present results show that tolerance following
repeated daily administration of phencyclidine in the
presence of one set of specified behavioral procedures did
not extend to behavioral effects of phencyclidine on responding under either similar or dissimilar procedures
occurring in different specified environmental circum-

127
stances. Tolerance to effects o f phencyclidine on TimeDelay responding in one c h a m b e r did n o t extend to
effects o f phencyclidine o n D R L responding in a different
chamber, for example, a n d tolerance to effects o f phencyclidine on F R responding did n o t extend to even the same
m a n i p u l a n d u m in a different chamber. I n contrast,
tolerance t h a t developed to effects o f phencyclidine o n
F R responding did extend to p e r f o r m a n c e on even a
different m a n i p u l a n d u m in a different schedule context
when these other conditions o c c u r r e d in the same experimental chamber. These effects are consistent with results
reported for b o t h rat (Greeley a n d Cappell 1985; Smith
1990a,b) a n d h u m a n (Shapiro a n d N a t h a n 1986) u n d e r
similar m u l t i - e n v i r o n m e n t procedures. It is n o t evident
f r o m the present procedure, o f course, whether the overriding influence o f physical e n v i r o n m e n t also occurs
when reinforcement contingencies and response t o p o graphies are m o r e m a r k e d l y different than those studied
here, a n d o n g o i n g experiments are studying these additional variables.
A singular effect o f a drug is n o t an inevitable consequence o f its acute administration (Morse et al. 1977;
Chrusciel 1978; M c K e a r n e y 1979; Barrett t 985; B r a d y
and Barrett 1986), and tolerance to effects o f a drug is n o t
an inevitable consequence o f its chronic administration
(Peele 1981; Barrett et al. 1989; B l a c k m a n 1989; Smith
1990a, b). Using e n v i r o n m e n t a l circumstances associated
with different experimental chambers, the present experim e n t has c o n t i n u e d to identify behavioral m a n i p u l a t i o n s
which can influence tolerance to the behavioral effects o f
drugs.

Acknowledgements. This research was supported by USPHS Grant

DA01987. I thank J.W. McKearney for comments on an earlier
form of the manuscript and V. DeStratis for technical assistance.

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