Cocaine Self-Administration and Seeking
Catheter implantation. Rats were prepared for cocaine
self-administration by surgical catheterization of the right jugular
vein. Briefly, rats were anesthetized with isoflurane (5% induction,
2.5% maintenance) in O2 and administered with the
nonsteroidal anti-inflammatory ketoprofen (2.5mg/kg, s.c. ).
Animals were placed on a heating pad from the induction of the
anesthesia to the end of the surgery. A handmade silastic catheter was
inserted into the jugular vein and the distal end was led to the back
between the scapulae. Rats were allowed to recover for 7 days and
flushed daily with 0.1ml sterile saline (0.9%), gentamicin (20mg/ml)
and heparin (100 UI/mL) in sterile saline to help protect against
infection and catheter occlusion.
Apparatus. Experiments were conducted in operant-conditioning
chambers, equipped with nose-pokes as operanda , a cue-light above
the active nose-poke, a house light and controlled by Imetronic
interfaces and software (Imetronic, Pessac, France).
Cocaine self-administration procedure . Rats were allowed to
self-administer cocaine (Cooper, France; 6g/L in saline solution 0.9%;
0.75mg/kg/infusion). Control rats received saline infusions according to
a yoked procedure, which consists of the delivery of an injection of
saline each time the paired « master » rat self-administered an
injection of cocaine. Rats were placed in the self-administration
chamber for 6h/day for ten sessions, using a Fixed Ratio 1 (FR1)
schedule of reinforcement. Response in the active nose poke resulted in
one intravenous (i.v.) cocaine infusion with the concomitant activation
of the light that remained on for 5s and then pulsed for 5s, followed by
a 5s time-out. Inactive nose-pokes were recorded but did not produce any
consequences. After the last self-administration session, rats remained
in their homecage for up to a month of forced abstinence. Animals were
then either used for electrophysiological recordings or tested for
cocaine-seeking behavior.
Cocaine-seeking behavior . Abstinent cocaine rats were re-exposed
to the operant chambers after 1 and 30 days of abstinence as previously
done (Chauvet et al., 2012). Active nose-pokes triggered cue-light and
syringe holder activation (similarly to self-administration sessions),
but rats were not connected to tubing and did not receive any cocaine
infusions. Cocaine-seeking behavior was measured for 1 h where active
and inactive responses were recorded. The same groups of rats were used
for each time point.