Journal Article

Enhanced sucrose pellet consumption induced by benzodiazepine-type drugs in squirrel monkeys: role of GABA sub(A) receptor subtypes

Huang, Shengming, Yin, Wenyuan, Platt, Donna M, Mattingly, Bruce A, Cook, James M, Rowlett, James K, Duke, Angela N

2006

Overview

Rationale: Benzodiazepine agonists characteristically increase food intake in humans and non-human subjects, and the underlying mechanisms of this effect are not understood completely. Objective: Compounds with selectivity for GABA sub(A) receptor subtypes were used to evaluate the role of GABA sub(A) receptors containing alpha 1 and alpha 5 subunits ( alpha 1GABA sub(A) and alpha 5GABA sub(A) receptors, respectively) in benzodiazepine-induced increases in sucrose pellet consumption. Materials and methods: Adult male squirrel monkeys (N=4-6), maintained under free-feeding conditions, were administered with intramuscular injections of the nonselective benzodiazepines diazepam and alprazolam, the alpha 1GABA sub(A)-preferring compounds zolpidem and zaleplon, or the alpha 5GABA sub(A)-preferring agonist QH-ii-066 before daily 10-min periods when sucrose pellets were available. In a separate experiment, observable behavioral effects (e.g., ataxia and procumbent posture) were quantified after administration of alprazolam, zaleplon, and QH-ii-066. To further assess the roles of GABA sub(A) receptor subtypes, zolpidem-induced increases in pellet consumption were re-evaluated after pretreatment with nonselective antagonist flumazenil, the alpha 1GABA sub(A)-preferring antagonist beta -carboline-3-carboxylate-t-butyl ester (BCCT), or QH-ii-066. Results: Alprazolam, diazepam, zolpidem, and zaleplon but not QH-ii-066 significantly increased sucrose pellet consumption. In addition, all agonists decreased locomotion and environment-directed behavior as well as engendered ataxia and procumbent posture. For all compounds except QH-ii-066, these behaviors occurred at doses similar to those that increased pellet consumption. Flumazenil and BCCT, but not QH-ii-066, antagonized zolpidem-induced increases in pellet consumption in a surmountable fashion. Conclusion: These results suggest that the alpha 1GABA sub(A) receptor subtype plays a key role in benzodiazepine-induced increases in consumption of palatable food, whereas the alpha 5GABA sub(A) receptor subtype may not be involved in this effect.

• Subject: Saimiri