EFFECTS OF ANABASEINE-RELATED ANALOGS ON RAT-BRAIN NICOTINIC RECEPTOR-BINDING AND ON AVOIDANCE BEHAVIORS

Several novel anabaseine-derived compounds were investigated with respect to their ability to displace high affinity [H-3]cytisine binding in rat brain membranes, as well as their ability to improve passive and active avoidance behaviors in nucleus basalis-lesioned rats. The relative potencies for displacement of 1 nM [H-3]cytisine binding IC50 in parentheses): anabaseine (70 nM) > DMAB (140 nM) = DMXB (150 nM) > anabasine (270 nM) > DMAC (420 nM). Passive avoidance behavior in bilaterally nucleus basalis-lesioned rats was improved by each of these drugs. to an extent comparable to that observed with (-)-nicotine. The relative potencies of these compounds for improving this behavior exhibited a pattern very similar to their affinities for displacing [H-3]cytisine binding (nicotine > anabaseine > DMXB > DMAB = DMAC > anabasine). Acquisition of active avoidance behavior was slower in unilaterally and bilaterally nucleus basalis-lesioned rats than unlesioned controls; (-)-nicotine improved acquisition behavior only in the former group. At doses that improved passive avoidance behavior, DMXB also improved acquisition of active avoidance behavior in unilaterally lesioned rats, while DMAB and DMAC did not. (-)Nicotine and DMXB had no effect on escape behavior in the active avoidance task at doses that improved retention of avoidance behavior itself. These results suggest that anabaseine and several of its analogs bind to brain alpha 4 beta 2 nicotinic receptors and mimic non-spatial, memory-related behaviors in a nicotine-like manner. (C) 1994 Wiley-Liss, Inc.