Enhanced sucrose pellet consumption induced by benzodiazepine-type drugs in squirrel monkeys: role of GABAA receptor subtypes
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- Duke, A.N., Platt, D.M., Cook, J.M. et al. Psychopharmacology (2006) 187: 321. doi:10.1007/s00213-006-0431-2
Benzodiazepine agonists characteristically increase food intake in humans and non-human subjects, and the underlying mechanisms of this effect are not understood completely.
Compounds with selectivity for GABAA receptor subtypes were used to evaluate the role of GABAA receptors containing α1 and α5 subunits (α1GABAA and α5GABAA 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 α1GABAA-preferring compounds zolpidem and zaleplon, or the α5GABAA-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 GABAA receptor subtypes, zolpidem-induced increases in pellet consumption were re-evaluated after pretreatment with nonselective antagonist flumazenil, the α1GABAA-preferring antagonist β-carboline-3-carboxylate-t-butyl ester (BCCT), or QH-ii-066.
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.
These results suggest that the α1GABAA receptor subtype plays a key role in benzodiazepine-induced increases in consumption of palatable food, whereas the α5GABAA receptor subtype may not be involved in this effect.