Vol. 281, Issue 1, 70-83, 1997

The Effects of Chronic Cocaine Self-Administration on the Menstrual Cycle in Rhesus Monkeys

Nancy K. Mello, Jack H. Mendelson, Maureen Kelly, Nicolas Diaz-Migoyo and J. Wallis Sholar

Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA 02178

Operant Behavioral Procedures and Apparatus
Monkeys lived in a well-ventilated stainless steel chamber equipped with an operant panel, a banana pellet feeder and a water dispenser. Drug injections were delivered by a syringe pump in a single pulse that dispensed 0.1 ml of fluid over 0.9 sec. The operation of the syringe pump (Model 981210, Harvard Apparatus, Inc., South Natick, MA) was audible to the monkey. Schedules of reinforcement were programmed by custom-designed software and run on Apple II GS computers.
Monkeys worked at an operant task for food and for i.v. cocaine injections on a second-order schedule of reinforcement (FR2 [VR:16S]) that required an average of 32 responses for each food pellet or cocaine injection. Food availability and cocaine availability conditions were associated with different colored stimulus lights (S+) projected on a translucent Plexiglas response key (2-in. diameter) in the center of the operant panel. The key was dark during time-out periods when responses had no programmed consequences. When a food pellet or drug injection was delivered, the appropriate colored stimulus light (S+) (red or green) was illuminated for 1 sec on one of the three circles (3/4-in. diameter) located in a vertical column below the response key. Flashes of the 1-sec colored stimulus lights (S+) also signaled the completion of each successive VR component of a second-order schedule response requirement. When cocaine was not available because of catheter loss, the response key was dark except during food sessions.
Each experimental day consisted of four food availability and four drug availability sessions. Food sessions began at 11 A.M., 3 P.M., 7 P.M. and 7 A.M. each day, and drug sessions began 1 hr later at 12 noon, 4 P.M., 8 P.M. and 8 A.M. Consecutive food and drug sessions were separated by time-out periods 2 hr (1-3 P.M., 5-7 P.M. and 9-11 A.M.) or 10 hr in duration (9 P.M.-7 A.M.). The response key was dark during time-out periods, and responses had no programmed consequences. Each food or drug session lasted 1 hr or until 100 banana pellets (1 gm) or 20 cocaine injections (0.10 mg/kg/injection) were delivered. Cocaine injections were limited to 80 per day (8 mg/kg/day) to minimize the possibility of adverse drug effects.

Surgical Procedures
After operant performance for food was stable on the final schedule of reinforcement and there was evidence of normal ovulatory base-line menstrual cycles, each monkey was surgically implanted with an i.v. double lumen silicon catheter (I.D. 0.028 in., O.D. 0.080 in.) under aseptic conditions. Monkeys were sedated with ketamine (5 mg/kg s.c.), and anesthesia was induced with sodium thiopental (10 mg/kg i.v.). Atropine (0.05 mg/kg) was given to reduce salivation. After insertion of an intratracheal tube, a surgical level of anesthesia was maintained with halothane (1-1.5% in oxygen). Catheters were implanted in the jugular or femoral vein and exited in the mid-scapular region. After surgery, monkeys were given 200,000 units of Combiotic Dihydrostreptomycin and Penicillin G i.m. on alternate days for a total of 5 injections. The i.v. catheter was protected by a tether system consisting of a custom-fitted nylon vest connected to a flexible stainless steel cable and fluid swivel (Spaulding Medical Products, Birmingham, AL), which permitted monkeys to move freely. Catheter patency was maintained by i.v. cocaine administration and a saline flush. Fluid swivel and catheter patency were checked manually each day. A short-acting barbiturate, methohexital sodium (3 mg/kg i.v.), was used to evaluate catheter patency, if necessary. The catheter was considered to be patent if i.v. administration of methohexital produced a loss of righting within 10 sec of its administration.