title: Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys.
abstract: The administration of alpha-2 adrenergic agonists to aged monkeys has been shown to ameliorate their cognitive deficits on the delayed response (DR) task, a test of spatial working memory (3,5). The present experiment tested whether the alpha-2 agonists, clonidine and guanfacine, would also improve working memory for object feature recognition, as tested by the delayed nonmatch-to-sample (DNMS) task. Five aged monkeys were trained on DNMS and were found to have mild performance deficits comparable to those reported previously for monkeys of similar age (32). However, during the subsequent two years of drug testing, the animals' baseline performance steadily improved, and conditions had to be made progressively more difficult to produce errors in performance. Clonidine and guanfacine significantly altered the DNMS performance of the aged monkeys, but drug-induced improvement was not as robust for DNMS as it was for DR. Clonidine produced a triphasic dose/response curve: Impairment was observed at both very low and high doses, while modest improvement was seen in the middle dose range (average maximal improvement of 21 +/- 2.4%). Although improvement could occasionally be replicated for some doses, the clonidine dose/response curves were remarkably inconsistent in the middle dose range. Similarly, doses of guanfacine which had previously produced optimal improvement on the DR task, produced only small but significant improvement in DNMS performance (average improvement of 11 +/- 3% for the 0.00011-0.000011 mg/kg dose range).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Section of Neuroanatomy, Yale Medical School, New Haven, CT 06510.
authors.forename: A F
authors.initials: AF
authors.lastname: Arnsten
authors.forename: P S
authors.initials: PS
authors.lastname: Goldman-Rakic
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000375:Aging / Q000523:psychology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006993:Hypnotics and Sedatives; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008568:Memory / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D013028:Space Perception / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives