3-[2,4-DIMETHOXYBENZYLIDENE]ANABASEINE (DMXB) SELECTIVELY ACTIVATES RAT ALPHA-7 RECEPTORS AND IMPROVES MEMORY-RELATED BEHAVIORS IN A MECAMYLAMINE-SENSITIVE MANNER

The alpha 7 nicotinic receptor agonist 3-[2,4-dimethoxybenzylidene]ana baseine (DMXB; GTS-21) was investigated for its ability to: (1) activa te a variety of nicotinic receptor subtypes in Xenopus oocytes; (2) im prove passive avoidance and spatial Morris water task performances in mecamylamine-sensitive manners in bilaterally nucleus basalis lesioned rats; and (3) elevate high-affinity [H-3]acetylcholine (ACh) and high -affinity alpha-[I-125]bungarotoxin binding in rat neocortex following 2 weeks of daily injections. DMXB (100 mu M) activated alpha 7 homo-o ligomeric receptors, without significant activity at alpha 2-, alpha 3 -and alpha 4-containing subtypes. Mecamylamine blocked rat alpha 7 rec eptors weakly if co-administered with agonist, but much more potently when pre-applied. Bilateral ibotenic acid lesions of the nucleus basal is interfered with passive avoidance and spatial memory-related behavi ors. DMXB (0.5 mg/kg, i.p.) improved passive avoidance behavior in les ioned animals in a mecamylamine-sensitive manner. DMXB (0.5 mg/kg 15 m in before each session) also improved performance in the training and probe components of the Morris water task. DMXB-induced improvement in the probe component but not the training phase was mecamylamine-sensi tive. [H-3]ACh binding was elevated after 14 days of daily i.p. inject ions with 0.2 mg/kg nicotine but not after 1 mg/kg DMXB. Neither drug elevated high-affinity alpha-[I-125]bungarorotoxin binding over this i nterval. (C) 1997 Elsevier Science B.V.