Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21

Gary W. Arendash, Gregory J. Sengstock, Paul R. Sanberg, William R. Kem

Research output: Contribution to journalArticlepeer-review

206 Scopus citations


The ability of two synthetic nicotine receptor ligands, GTS-21 and DMAB, to chronically enhance the cognitive function of aged rats was evaluated in three diverse tasks and compared to the cognition-enhancing effects of nicotine administration. 15 min prior to daily behavioral testing, aged 22-24 month old rats received an i.p. injection of nicotine (0.2 mg/kg), GTS-21 (1 mg/kg), DMAB (2 mg/kg), or saline vehicle and were tested in either one-way active avoidance pole jumping, Lashley III maze, or a 17-arm radial maze. GTS-21 pretreatment was as effective as nicotine for enhancing the acquisition of aged rats in both one-way active avoidance and Lashley III maze training. In 17-arm radial maze testing, GTS-21 improved both general learning and reference (long-term) memory to the same extent as nicotine. Although DMAB pretreatment enhanced reference memory in 17-arm radial maze testing to the same extent as nicotine, it did not affect general learning in this complex task and did not exert any cognition-enhancing effects in Lashley III maze training. These results indicate that GTS-21 has cognition-enhancing abilities in aged rats that are comparable to those of nicotine in a variety of behavioral tasks. Since GTS-21 acts preferentially on brain nicotinic receptors and is less toxic than nicotine, these results further indicate that GTS-21 may have substantive therapeutic value in the treatment of age-associated memory impairment (AAMI) and/or Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)252-259
Number of pages8
JournalBrain Research
Issue number2
StatePublished - Mar 20 1995
Externally publishedYes


  • Acetylcholine
  • Age-associated memory impairment
  • Aging
  • Cognition-enhancing
  • Nicotine
  • Nicotinic agonist
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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