A contingent, conditioned suppression of eating following chronic benzodiazepine-induced hyperphagia

While the hyperphagic effect of chlordiazepoxide (CDP) has been reported by some to be enhanced with chronic drug treatment, the processes underlying this phenomenon are not well understood. In the present study, it was predicted that following chronic exposure to CDP-induced hyperphagia, animals given a placebo in place of their usual drug injection might be expected to exhibit evidence of a conditioned, drug-like response. Such a finding would then be consistent with an underlying process of behavioral sensitization. In Experiment 1a, Male Sprague-Dawley rats were randomly assigned to one of two groups receiving intraperitoneal (IP) injections of either 5 mg/kg CDP (Group CDP) or physiological saline (1 ml/kg; Group SAL) administered over 15 drug treatment days. Thirty minutes after each injection, all animals were given 30 min access to sweetened condensed milk. A significant enhancement of CDP-induced hyperphagia was observed over treatment sessions, confirming an earlier report. Unexpectedly, in the Placebo Test, the CDP animals exhibited a suppression of milk consumption relative to that of the SAL group. Using the same animals, this finding was successfuly replicated in Experiment 1b. In Experiment 2, it was hypothesized that if this conditioned, drug-opposite response were to reflect the involvement of some underlying compensatory, homeostatic mechanism, then it should only be observable under food-contingent conditions of chronic drug treatment. This prediction was confirmed. While animals given chronic CDP treatments (5 and 15 mg/kg) followed by milk presentation (Contingent Group CDP/C) eventually exhibited a suppressed eating response in a Placebo Test, animals with an identical drug history, but with no opportunity to consume milk until 24 hr after each drug treatment (Noncontingent, Group CDP/NC) failed to show such a conditioned response relative to their respective saline control group. The implications of this surprising finding are discussed in relation to present theories of benzodiazepine hyperphagic action.