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

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