Introduction: The α2-adrenergic receptor agonist clonidine was examined for its ability to improve working memory in monkeys. Materials and methods: Clonidine (0.116-34.8 μg/kg) was administered to six pigtail macaques in their performance of a computer-assisted delayed matching-to-sample (DMTS) task. Results and discussion: During DMTS sessions initiated 1 hour after dosing, there was a slight improvement in mean task accuracy (long delay trials; 0.116-μg/kg). On the following day, there was continued and added improvement in accuracies associated with the long delay trials. On the day following 1.16-μg/kg, the entire memory retention curve was shifted to the right of vehicle. When the animals were again tested 48 hours after dosing (no pretreatment), these two patterns of task enhancement were continued and enhanced. Mean task accuracy associated with long delay trials was significantly increased by 14.2% trials correct when animals were originally treated with 0.116-μg/kg of clonidine. Mean task accuracy associated with medium delay trials was significantly increased by 11.8% trials correct when animals were treated with 1.16-μg/kg. On the sixth day after clonidine, task accuracies were still significantly improved during medium delay trials after 0.116-μg/kg. Median sample and choice latencies were not significantly influenced by clonidine treatment. These findings are consistent with the ability of clonidine to induce a protracted improvement in aspects of working memory. Conclusion: Early (attentional) and late (retention) components of memory appeared to be differentially sensitive to the dose of clonidine. Central α2-adrenergic receptors should be considered legitimate drug targets for future compound development for cognition enhancement.
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