Ketamine retards recovery from reward downshift and supports conditioned taste aversion.
Pharmacology, biochemistry, and behavior – October 28, 2023
Source: PubMed
Summary
Ketamine's effects on emotional memory reveal an unexpected dark side: the drug can actually intensify negative experiences with food. When rats experienced a switch from high to low sugar water, ketamine made them more reluctant to drink, creating lasting aversive memories. This demonstrates how the drug influences reward processing and taste aversion, suggesting complex interactions between ketamine, frustration, and memory formation.
Abstract
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.