NICOTINE-INDUCED INHIBITION IN MEDIAL SEPTUM INVOLVES ACTIVATION OF PRESYNAPTIC NICOTINIC CHOLINERGIC RECEPTORS ON GAMMA-AMINOBUTYRIC ACID-CONTAINING NEURONS

Neuronal responses to drugs acting on nicotinic cholinergic receptors (nAChRs) were examined in the rat medial septal area by using an in vi vo extracellular single-unit recording technique. In the medial septal area, iontophorectically applied nicotine inhibited neuronal activity in 45% of the neurons, but had no effect on the remaining neurons. Di hydro-beta-erythroidine application to neurons in the medial septal ar ea not only blocked nicotine-induced inhibition, but also reduced spon taneous neuronal activity of the neurons. When Mg++ was applied iontop horetically to block presynaptic neurotransmitter release, a significa nt reduction in spontaneous neural activity also was observed. No furt her reduction of spontaneous activity by dihydro-beta-erythroidine occ urred in the presence of Mg++, suggesting an apparent tonic excitatory input to the majority of neurons in the medial septal area under the control of presynaptic nAChRs. Mg++ abolished the nicotine-induced inh ibition in the medial septal area without having an effect on nicotine -induced inhibition in the cerebellum. Thus, these data provide eviden ce that the inhibitory effects of nicotine in the medial septum are du e to an action on presynaptic nAChRs, controlling the release of an in hibitory neurotransmitter. Of the medial septal neurons which showed n o response to nicotine, nicotine produced excitation in 21% of the cel ls after Mg++ application, indicating that nicotine can have a direct action on postsynaptic nAChRs, in addition to its presynaptic action, in the medial septum. Finally, application of the gamma-aminobutyric a cid antagonist bicuculline reduced the nicotine-induced inhibition on the majority of medial septal neurons tested, but was without effect o n the inhibition produced by nicotine on cerebellar Purkinje neurons. Consequently, it can be concluded that the nicotine-induced inhibition in the medial septum is the result of gamma-aminobutyric acid release due to its action on presynaptic nAChRs present on gamma-aminobutyric acid-containing terminals.