DMXB selectively activates rat a 7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner

w x Ž . Ž . The a 7 nicotinic receptor agonist 32,4-dimethoxybenzylidene anabaseine DMXB; GTS-21 was investigated for its ability to: 1 Ž . activate a variety of nicotinic receptor subtypes in Xenopus oocytes; 2 improve passive avoidance and spatial Morris water task Ž . w3 x performances in mecamylamine-sensitive manners in bilaterally nucleus basalis lesioned rats; and 3 elevate high-affinity H acetylchoŽ . w125 x Ž . line ACh and high-affinity aI bungarotoxin binding in rat neocortex following 2 weeks of daily injections. DMXB 100 mM activated a 7 homo-oligomeric receptors, without significant activity at a 2-, a 3and a4-containing subtypes. Mecamylamine blocked rat a 7 receptors weakly if co-administered with agonist, but much more potently when pre-applied. Bilateral ibotenic acid lesions of the Ž . nucleus basalis interfered with passive avoidance and spatial memory-related behaviors. DMXB 0.5 mgrkg, i.p. improved passive Ž . avoidance behavior in lesioned animals in a mecamylamine-sensitive manner. DMXB 0.5 mgrkg 15 min before each session also improved performance in the training and probe components of the Morris water task. DMXB-induced improvement in the probe w3 x component but not the training phase was mecamylamine-sensitive. H ACh binding was elevated after 14 days of daily i.p. injections w125 x with 0.2 mgrkg nicotine but not after 1 mgrkg DMXB. Neither drug elevated high-affinity aI bungarorotoxin binding over this interval. q 1997 Elsevier Science B.V.