Cooperation Counts

Dr. Andrew Winterborn of the University of Rochester Medical Center trains rhesus macaques to take juice from syringes.

Our study was conducted on caged animals during their semi-annual testing and physical exam for tuberculosis, with the goal of comparing the efficacy of two orally dosed anesthetic regimens for chemical immobilization in rhesus macaques versus the standard protocol of intramuscular ketamine. The effects of the dosing route on hematological stress were also evaluated.

One of the major components for the success of this study required that all animals accept oral dosing, which was achieved through operant conditioning—what is commonly known as positive reinforcement. The 5-day-a-week, month-long task of training the macaques was broken down into three steps. The first step of shaping the desired behavior involved establishing a positive relationship between the macaque and the trainer. This objective was achieved when the animal approached the front of the cage voluntarily after the trainer entered the room.

Step two involved restricting the animal to the front quarter of the cage by using the squeeze device. A raisin was placed on the tip of a fruit juice-filled 5 cc syringe and presented to the animal. This encouraged the animal to approach the syringe with his or her mouth or fingers to take the fruit, at which point the trainer gently squirted a little juice into the macaque’s mouth or hand. This process was repeated until all of the animals voluntarily approached the syringe and drank all of the juice. Once an animal readily suckled or licked the juice from the syringe, he or she was rewarded with a grape or small piece of fruit. Finally, in step three, animals were offered the juice without being confined to the front of the cage. Once again, the macaques were rewarded for drinking all of the juice from the syringes.

By the end of the month, 16 of the 18 animals (88.89 percent) had been successfully taught to drink juice from a syringe. Four of the 18 animals were immediately interested in the syringe and readily came forward to drink the liquid. The remaining 14 required more intensive operant training, with 12 finally succeeding. The time constraint was the limiting factor in training the remaining two animals. One month was not sufficient, although some progress was made. They would both approach the front of the cage when observed and would take treats from the end of the syringe, though they would not drink. Several different liquids were used to see if this would facilitate training, without success.

Throughout the month, each training session lasted a maximum of five minutes, and if the desired behavior was achieved in less time, the session was stopped. The average total training time per animal, excluding the time invested in the two animals who did not successfully accept oral dosing, was 13 ± 8.6 minutes. The shortest training period was three minutes, with the animal accepting oral dosing during the first training session. The longest training period was 35 minutes.

Operant conditioning for oral dosing has many applications. If macaques are trained to accept liquid from syringes, they can receive test compounds in pharmaceutical testing by voluntarily accepting the liquid and being rewarded for it. This functions as an alternative to the current practice of gavage. In addition, oral dosing has implications for husbandry and veterinary procedures. If an animal is trained to drink from a syringe, medication can be given orally instead of injected. In all instances, the primate is an active participant in the procedure. The key to effective operant training is finding a palatable fluid for each individual animal and identifying a reward when they ingest all of the fluids.

Successful oral dose training allowed for the evaluation of the efficacy of oral dosing for sedation. Our study concluded that oral dosing alone was not sufficient to achieve a state of sedation to allow for safe handling. However, animals who received ketamine and medetomidine, followed by supplemental intramuscular ketamine, did have a smoother induction and recovery. Serum cortisol and glucose levels were unchanged across all groups. In contrast, differences were observed in the leukogram profiles, indicating that oral dosed animals experienced a higher level of stress. It was hypothesized that this was a result of their light state of anesthesia, not a direct result of oral dosing.