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  • Title: Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21.
    Author: Arendash GW, Sengstock GJ, Sanberg PR, Kem WR.
    Journal: Brain Res; 1995 Mar 20; 674(2):252-9. PubMed ID: 7796104.
    Abstract:
    The ability of two synthetic nicotine receptor ligands, TGS-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 (.02 mg/kg), GTS-21 (1 mg/kg), DMAB (2mg/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 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, thses 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.
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