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.