Allosteric modulation of GAB AA receptor subtypes: Effects on visual recognition and visuospatial working memory in rhesus monkeys

Paul L. Soto, Nancy A Ator, Sundari K. Rallapalli, Poonam Biawat, Terry Clayton, James M. Cook, Michael R. Weed

Research output: Contribution to journalArticle

Abstract

Non-selective positive allosteric modulators (PAMs) of GABAA receptors (GABAARs) are known to impair anterograde memory. The role of the various GABAAR subtypes in the memory-impairing effects of non-selective GABAAR PAMs has not been fully elucidated. The current study assessed, in rhesus monkeys, effects of modulation of alpha;1, alpha;2/3, and alpha;5GABAARs on visual recognition and spatial working memory using delayed matching-to-sample (DMTS) and self-ordered spatial search (SOSS) procedures, respectively. The DMTS procedure (n=8) involved selecting a previously presented 'sample' image from a set of multiple images presented after a delay. The SOSS procedure (n=6) involved touching a number of boxes without repeats. The non-selective GABAAR PAM triazolam and the α1GABAA preferential PAMS zolpidem and zaleplon reduced accuracy in both procedures, whereas the α5GABAA preferential PAMs SH-053-20F-R-CH3 and SH-053-20F-S-CH3, and the α2/3GABAA preferential PAM TPA023B were without effects on accuracy or trial completion. The low-efficacy α5GABAAR negative allosteric modulator (NAM) PWZ-029 slightly increased only DMTS accuracy, whereas the high-efficacy α5GABAAR NAMs RY-23 and RY-24 did not affect accuracy under either procedure. Finally, the slopes of the accuracy dose-effect curves for triazolam, zolpidem, and zaleplon increased with box number in the SOSS procedure, but were equivalent across DMTS delays. The present results suggest that (1) a1GABAARs, compared with α2/3 and α5GABAARs, are primarily involved in the impairment, by non-selective GABAAR PAMs, of visual recognition and visuospatial working memory in nonhuman primates; and (2) relative cognitive impairment produced by positive modulation of GABAARs increases with number of locations to be remembered, but not with the delay for remembering.

Original languageEnglish (US)
Pages (from-to)2315-2325
Number of pages11
JournalNeuropsychopharmacology
Volume38
Issue number11
DOIs
StatePublished - Oct 2013

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GABA-A Receptors
Macaca mulatta
Short-Term Memory
zaleplon
Triazolam
Primates
Recognition (Psychology)

Keywords

  • Benzodiazepine
  • Cognition
  • Delayed-matching-to-sample
  • GABA receptor
  • Rhesus monkey
  • Self-ordered spatial search

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Medicine(all)

Cite this

Allosteric modulation of GAB AA receptor subtypes : Effects on visual recognition and visuospatial working memory in rhesus monkeys. / Soto, Paul L.; Ator, Nancy A; Rallapalli, Sundari K.; Biawat, Poonam; Clayton, Terry; Cook, James M.; Weed, Michael R.

In: Neuropsychopharmacology, Vol. 38, No. 11, 10.2013, p. 2315-2325.

Research output: Contribution to journalArticle

Soto, Paul L. ; Ator, Nancy A ; Rallapalli, Sundari K. ; Biawat, Poonam ; Clayton, Terry ; Cook, James M. ; Weed, Michael R. / Allosteric modulation of GAB AA receptor subtypes : Effects on visual recognition and visuospatial working memory in rhesus monkeys. In: Neuropsychopharmacology. 2013 ; Vol. 38, No. 11. pp. 2315-2325.
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