A NOVEL NICOTINIC AGONIST FACILITATES INDUCTION OF LONG-TERM POTENTIATION IN THE RAT HIPPOCAMPUS

Long-term potentiation (LTP) can be modulated by a number of neurotran smitter receptors including muscarinic and GABAergic receptor types. W e have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [I-125]alpha-bungarotoxin and [H-3]acetylchol ine binding in rat brain. Xenopus oocyte studies demonstrated that DMX B has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic rec eptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activa tion is capable of modulating the induction of long-term potentiation.