Ketamine retards recovery from reward downshift and supports conditioned taste aversion

Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist with antidepressant, anxiolytic, and memory effects in clinical and preclinical studies. The present studies investigated the behavioral effects of ketamine in animals exposed to a consummatory successive negative contrast (cSNC) task involving unexpected reward downshift, negative emotion (frustration), and aversive memory. Food-restricted male rats had 5-min access to 32 % sucrose in each of 10 preshift sessions followed by 4 % sucrose in 4 postshift sessions. Unshifted controls had access to 4 % sucrose during all 14 sessions. Ketamine (10 mg/kg, ip) was injected 30 min before sessions 11 and 12 (Experiment 1) or immediately after session 11 (Experiment 3). The results showed that both pre- and postdownshift session injection of ketamine increased consummatory suppression, as Group 32/Ket exhibited lower sucrose intake than Groups 32/Sal, 4/Ket, and 4/Sal. These effects extended beyond the day(s) of injection. Experiments 2 and 4 showed that the same dose, route of administration, and time of injection induced significant conditioned taste aversion to 4 % sucrose, in the absence of reward downshift. These data suggest that ketamine induces an aversive state that may summate with frustration induced by reward downshift in the cSNC task and also support a conditioned taste aversion to 4 % sucrose in the absence of reward downshift. Implications for these and other experiments involving pre- and postsession administration of ketamine are discussed.