Supplementary Materials and Methods
Housing and Animal Care
Rats. Between sessions, rats were housed individually in clear plastic cages (43 X 22 X
20 cm) in a temperature- (21-23 C) and light- (08:00 h on, 20.00 h off) controlled vivarium.
Rats were maintained at 90% of an upwardly adjusting ad libitum body weight throughout the
duration of the study by providing 16 g of food per day. Rats had unlimited access to water in
their home cages.
Monkeys. Between sessions, monkeys lived in individual home cages (196 X 151 X 59
cm) in a temperature- (21-23 C) and light- (06:30 h on, 18:30 h off) controlled vivarium.
Monkeys had unrestricted access to food (Teklad Monkey Diet, fruit) and water in their home
cages.
Experimental Chambers
Rats. Experimental chambers (Med Associates, East Fairfield, Vt., USA) were each
equipped with two response levers positioned to the left and right of a center-mounted food
receptacle. Connected to the food receptacle was a pellet dispenser, which delivered 45-mg
food pellets. A white stimulus light was mounted above each lever. Each chamber was outfitted
with a single channel fluid swivel and spring leash assembly that were connected to a
counterbalanced arm assembly (Med Associates). A sound-attenuating cubicle (Med
Associates), equipped with an overhead light to provide general illumination, a fan to provide
ventilation, and an 8 ohm speaker to provide white background noise, enclosed each chamber.
Motor-driven syringe pumps (Med Associates) used for drug delivery were located outside the
sound-attenuating cubicle. The pumps were programmed to deliver cocaine into the catheter at
a rate of 0.05 ml/sec. A PC-compatible computer programmed in Medstate Notation and
connected to an interface (Med Associates) controlled experimental events in an adjacent room.
Monkeys. Daily sessions were conducted in ventilated, sound-attenuated chambers with
white background noise (MED Associates). Within the chambers, monkeys sat in Plexiglas
chairs (MED Associates) facing a panel equipped with response levers and red and white
stimulus lights, which could be illuminated to serve as visual stimuli. One response lever was
mounted on the wall of the chair in front of the monkey. Each press of a lever with a minimum
downward force of approximately 0.25N produced an audible click and was recorded as a
response. Catheters were connected to a motor-driven syringe pumps (MED Associates)
located outside the chamber. The pumps were programmed to deliver cocaine or vehicle (0.9%
saline solution) into the catheter at a rate of 0.18 ml/sec. Behavioral observation studies were
conducted in a ventilated, transparent Plexiglas arena (114cm in length × 122cm in width ×
213cm in height) situated in a lighted room, separate from other animals. The arena was
equipped with perches, suspended plastic chains, and a wood-chip bedding to permit a range of
species-typical behaviors. A videocamera was positioned 1m in front of the chamber to record a
subject’s behavior continuously during the session. Experiments were controlled, and data were
recorded via interfaces (Med Associates) and PC-compatible computers located in an adjacent
room.
Surgery
Rats were anesthetized with i.p. injections of 90 mg/kg ketamine plus 10 mg/kg xylazine.
Incisions were made to expose the right jugular vein and skull, and a catheter made from silicon
tubing (i.d. =0.020 inches, o.d. =0.037 inches) was subcutaneously positioned between these
two points. After insertion into the vein, the proximal end of the catheter was anchored to the
muscles underlying the vein with surgical silk and a small piece of 0.5-mm mesh. The distal end
of the catheter was attached to a 22-gauage L-shaped pedestal mount (Plastics One, Roanoke,
VA.). The cannula was attached to the skull with three stainless-steel screws and dental cement
and sealed with a crimped piece of Teflon tubing and a plastic cap when not in use. Wounds
were treated daily until healed with nitrofutazone powder. The catheters were maintained by
flushing them daily with 0.1 ml of a 0.9% saline solution containing 0.3 IU heparin (LymphoMed,
Inc., Rosemont, Ill.), 6.7 mg timentin (SmithKline Beecham Pharmaceuticals, Philadelphia, PA.).
Catheters were checked daily for leaks and were checked weekly, or as needed, for function by
infusing 0.1 ml of a solution containing 1.0 mg methohexital sodium (Brevital, Eli Lilly and Co.,
Indianapolis, IND.) and noting the presence or absence of sedation. If a catheter leaked or the
vein was non-functional, a new catheter was implanted into the right femoral vein.
Monkeys were implanted with a chronic indwelling venous catheter (polyvinyl chloride;
i.d., 0.64 mm; o.d., 1.35 mm) under 1% isoflurane anesthesia and aseptic conditions. One end
of the catheter was passed via a femoral or jugular vein to the level of the right atrium. The
distal end of the catheter was then externalized through a small incision in the skin to a midscapular exit site and occluded using a sterile stainless steel obturator until access was
required. Catheters were flushed daily with 0.9% saline solution and were sealed with stainless
steel obturators when not in use. Monkeys wore custom-made nylon-mesh jackets (Lomir
Biomedical, Toronto, ON, Canada) at all times to protect the catheter.
Figure S1. Schematic of Experimental Design
Experiment 1
Self-Administration
Baseline
Extinction
Training
Extinction
Retention
Self-Administration
Reacquisition
DCS (0.5 hr pre)
Experiment 2a
Self-Administration
Baseline
Self-Admin Extinction
Session
Retention
Self- Administration
Reacquisition
DCS (0.5 hr pre)
Experiment 2b
Self-Administration No -Extinction Extinction
Baseline
Session
Retention
Self-Administration
Reacquisition
DCS (0.5 hr pre)
Experiment 3a
Experiment 3b
Self-Administration
Baseline
Extinction
Training
Extinction
Retention
Self-Administration
Reacquisition
DCS (0 hr post; with or without handling)
Experiment 3c
Self-Administration
Baseline
Extinction
Training
Extinction
Retention
Self-Administration
Reacquisition
DCS (6 hr post; with handling)
Table S1. Behavioral Categories. Adapted from Platt et al. 2000
Locomotion
Any two or more directed steps in the horizontal or
vertical plane
Object exploration
Any tactile or oral manipulation of features of the
observation arena
Foraging
Sweeping and/or picking through wood-chip substrate
Grooming
Picking, scraping, spreading or licking of fur
Scratching
Rapid movement of digits through fur in a rhythmic,
repeated motion
Vocalization
Any utterance including chirps, twitters, peeps, etc.
Rest posture
Species-typical posture: crouched on hind legs, hunched
back, tail wrapped around upper body
Static posture
Maintenance of a rigid, atypical posture
Procumbent
loose-limbed, sprawled posture; unable to maintain upright
position
Visual scan
Directed eye and/or head movements, usually from a
sitting position
Other
Any notable behavior not defined above (e.g., yawn,
sneeze)
Supplementary Results
Rats
Monkeys
Vehicle
80
60
300
Responses
Responses
Vehicle
400
40
20
200
100
0
0
2
4
6
8
10 12 14 16 18 20 22 24
2
Sequential Components (10min)
10 12 14 16 18 20 22 24
DCS 3mg/kg
300
Responses
Responses
8
400
60
40
200
100
20
0
0
2
4
6
8
2
10 12 14 16 18 20 22 24
DCS 30 mg/kg
80
4
6
8
10 12 14 16 18 20 22 24
Sequential Components (10min)
Sequential Components (10min)
DCS 10mg/kg
400
60
300
Responses
Responses
6
Sequential Components (10min)
DCS 15mg/kg
80
4
40
20
200
100
0
0
2
4
6
8
10 12 14 16 18 20 22 24
2
Sequential Components (10min)
4
6
8
10 12 14 16 18 20 22 24
Sequential Components (10min)
Figure S2: Responding by individual subjects during extinction training in Experiment 1. Values
are the number of lever presses per sequential 10-min bin following vehicle (Veh; top panels),
intermediate doses of DCS (15 and 3 mg/kg; middle panels), and higher doses of DCS (30 and
10 mg/kg; bottom panels) in individual rats (left panels) and monkeys (right panels),
respectively. A different symbol is used for each subject.