Oral d-amphetamine and ketamine self-administration by rhesus monkeys: Effects of food deprivation

Orally delivered d-amphetamine and ketamine were tested for their ability to maintain self-administration behavior by substituting them for phencyclidine. Six monkeys were trained to self-administer phencyclidine (0.25 mg/ml) and water under a concurrent fixed-ratio 16 schedule during 3-hr sessions. At the start of the experiment the monkeys were maintained at 85% of their free-feeding body weights. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. When d-amphetamine (0.0156-0.25 mg/ml) was substituted for phencyclidine, maximum drug intake ranged from 1 to 1.5 mg/kg among three monkeys, and response rates were greatest at the three lower concentrations (0.0156-0.0625 mg/ml). When monkeys were food satiated, maximum d-amphetamine intake ranged from 0.3 to 1.1 mg/kg among three monkeys, and response rates were greatest at the higher concentrations (0.125-0.25 mg/ml). In the second experiment, ketamine (0.125-4 mg/ml) was substituted for phencyclidine (0.25 mg/ml). Maximum ketamine intake ranged from 14.5 to 44.5 mg/kg among three monkeys, and maximum responding occurred at the 0.25- and 1-mg/ml concentrations. Food satiation reduced maximum ketamine intake (7.1-22.3 mg/kg) among three monkeys. With both d-amphetamine and ketamine, responding was evenly distributed throughout the session during food satiation, whereas during food deprivation, most responding occurred within the 1st hr of the session. These results showed that substitution procedures can be effectively used to demonstrate the reinforcing effects of orally delivered d-amphetamine and ketamine. Food deprivation generally increased drug-reinforced responding; however, at the higher concentrations of drug this difference was greatly diminished. Thus, the magnitude of the food deprivation effect was greatly altered by changes in drug concentration.