title: Protracted cognitive effects produced by clonidine in Macaca nemestrina performing a delayed matching task.
abstract: BACKGROUND
  The alpha(2)-adrenergic receptor agonist clonidine was examined for its ability to improve working memory in monkeys.
  
  
  METHODS
  Clonidine (0.116-34.8 microg/kg) was administered to six pigtail macaques in their performance of a computer-assisted delayed matching-to-sample (DMTS) task.
  
  
  CONCLUSIONS
  During DMTS sessions initiated 1 hour after dosing, there was a slight improvement in mean task accuracy (long delay trials; 0.116-microg/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-microg/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-microg/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-microg/kg. On the sixth day after clonidine, task accuracies were still significantly improved during medium delay trials after 0.116-microg/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.
  
  
  CONCLUSIONS
  Early (attentional) and late (retention) components of memory appeared to be differentially sensitive to the dose of clonidine. Central alpha(2)-adrenergic receptors should be considered legitimate drug targets for future compound development for cognition enhancement.
authors.affiliation: Alzheimer's Research Center, Medical College of Georgia, Augusta, GA 30912-2300, USA. jbuccafu@mcg.edu
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Buccafusco
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Webster
authors.forename: Alvin V
authors.initials: AV
authors.lastname: Terry
authors.forename: Nancy
authors.initials: N
authors.lastname: Kille
authors.forename: Donna
authors.initials: D
authors.lastname: Blessing
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008254:Macaca nemestrina; D008297:Male; D008568:Memory / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D003000:Clonidine
references.citation: J Physiol. 1999 Sep 1;519 Pt 2:439-49
references.pmid: 10457061
references.citation: Behav Pharmacol. 2006 Nov;17(7):581-7
references.pmid: 17021390
references.citation: Cereb Cortex. 1993 Jul-Aug;3(4):304-12
references.pmid: 8400808
references.citation: J Psychopharmacol. 2007 Mar;21(2):171-8
references.pmid: 17329297
references.citation: J Clin Psychopharmacol. 1999 Oct;19(5):444-9
references.pmid: 10505586
references.citation: Psychoneuroendocrinology. 1993;18(1):45-55
references.pmid: 8097332
references.citation: Neuropsychopharmacology. 2000 Sep;23(3):240-9
references.pmid: 10942848
references.citation: J Neurosci. 1988 Nov;8(11):4287-98
references.pmid: 2903226
references.citation: Cogn Behav Neurol. 2006 Dec;19(4):204-7
references.pmid: 17159617
references.citation: Psychopharmacology (Berl). 2002 Jul;162(3):304-12
references.pmid: 12122489
references.citation: Trends Pharmacol Sci. 2005 Jul;26(7):352-60
references.pmid: 15946748
references.citation: J Pharmacol Exp Ther. 1999 Feb;288(2):798-804
references.pmid: 9918591
references.citation: Neurotoxicol Teratol. 1998 Sep-Oct;20(5):493-502
references.pmid: 9761587
references.citation: CNS Drug Rev. 2005 Autumn;11(3):229-52
references.pmid: 16389292
references.citation: Behav Neural Biol. 1992 Sep;58(2):152-8
references.pmid: 1456935
references.citation: Cell. 2007 Apr 20;129(2):397-410
references.pmid: 17448997
references.citation: Learn Mem. 2006 Nov-Dec;13(6):770-6
references.pmid: 17101879
references.citation: Psychopharmacology (Berl). 1986;88(3):374-80
references.pmid: 3083458
references.citation: Neuropsychopharmacology. 1999 Nov;21(5):611-21
references.pmid: 10516957
references.citation: J Child Adolesc Psychopharmacol. 2007 Aug;17(4):393-406
references.pmid: 17822336
references.citation: Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):231-41
references.pmid: 9164577
references.citation: Neuroscience. 1999;92(3):975-82
references.pmid: 10426537
references.citation: Neuropsychopharmacology. 1999 May;20(5):460-70
references.pmid: 10192826
references.citation: J Paediatr Child Health. 2007 Jan-Feb;43(1-2):19-24
references.pmid: 17207050
references.citation: Pharmacol Biochem Behav. 1991 May;39(1):79-84
references.pmid: 1924516