2.8. Intravenous Catheter Implantation and Methamphetamine Self-Administration Training

This study assessed the effects of passive immunization with anti-MA AB sera on reinstatement of drug-seeking behavior in rats trained to self-administer IV MA. Prior to surgery, rats were trained to lever press for food (30 min sessions) under a continuous reinforcement schedule until consistent lever press responding was achieved (e.g., obtaining the maximum number of 50 food reinforcers on two occasions in 30 min or less). Rats were then surgically implanted with indwelling intravenous jugular catheters as we conducted previously with slight modifications [41]. The rat was anesthetized with isoflurane anesthesia (2–3%) and surgical sites (right ventral neck area and dorsal midline mid-scapular) prepared by first shaving then cleaning the areas with Betadine solution followed with 70% ethanol. The rat was placed supine and the jugular vein located and catheter inserted into the right vein and secured with 2.0 silk. A dorsal mid-scapular subcutaneous space was then dissected approximately 2.5 cm in diameter for ventral access button placement. Using a curved blunt hemostat, a subcutaneous passage was made for the catheter from the jugular incision to the mid-scapular incision. The catheter was then pulled through the mid-scapular incision site to the jugular neck area and clamped with a needle nose hemostat. A vascular access “button” was then attached to the end of the catheter to permit use of a miniature PinPort system (Instech Laboratories, Inc., Plymouth Meeting, PA, USA). The incisions were then sutured closed using monofilament polypropylene suture. Rats were allowed at least 7 days recovery before beginning MA self-administration sessions. Catheters were flushed daily with a heparinized saline solution.

MA self-administration sessions were conducted using standard operant chambers (Coulbourn Instruments, Holliston, MA, USA) enclosed in sound-attenuating cubicles (Coulbourn Habitest isolation cubicle). Each chamber was equipped with two levers located on either side of an access area into which food pellets could be delivered. Within the operant chamber were a house light and two sets of three, colored cue lights, one above each lever. Graphic State Notation (version 4.0; Coulbourn Instruments) was installed on a PC and used to program experimental and stimulus parameters and tabulate data.

MA self-administration training sessions (2 h) were initiated after recovery from surgery. Rats were placed in the operant chambers and their catheter/cannula system was attached to a syringe pump system that consisted of an infusion pump (Razel model A) with a 20-mL glass syringe connected to a tether (Instech Laboratories, Inc., Plymouth Meeting, PA, USA). The tether was connected to the animals’ PinPort assembly using Tygon tubing protected by a metal spring and secured to the animal’s back port via a Luer-lock attachment. Initially, rats were given one priming infusion and then one depression of the active lever resulted in an intravenous infusion of 100-µL injection of MA under a fixed ratio 1 (FR1) schedule of reinforcement in which a dose of 0.125 mg/kg was delivered per infusion. The MA infusion was delivered over a 10 s period, followed by a 20 s time-out. Cue lights were illuminated above the active and inactive levers. Cue and house lights were turned off during the entire infusion and time-out periods. Active lever presses emitted during the infusion time or during the time-out period were tabulated but did not result in any further MA delivery. Presses on the inactive lever were tabulated but had no programmed consequences. When MA showed control over behavior under the FR1 schedule of reinforcement, the FR requirement was raised to FR2, the schedule used for the remainder of the experiment. Once consistent self-administration responding was shown (number of reinforcers earned showed <20% variability over two consecutive days), tests for dose-related responding to MA were initiated followed by reinstatement tests as described below.