Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21.
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.
Arendash
G W
GW
Department of Biology, University of South Florida, Tampa 33620, USA.
Sengstock
G J
GJ
Sanberg
P R
PR
Kem
W R
WR
D000375:Aging / Q000523:psychology*; D000691:Anabasine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001597:Benzylidene Compounds / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
C094402:3-(4-dimethylaminobenzylidene)anabaseine; D001597:Benzylidene Compounds; D018722:Nicotinic Agonists; D011619:Psychotropic Drugs; D011725:Pyridines; D009538:Nicotine; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D000691:Anabasine