Modulation of synaptic transmission by nicotine and nicotinic antagonists in hippocampus

Using rat hippocampal slices, we studied the effects of nicotine and three antagonists of neuronal nicotinic receptors on excitatory and inhibitory tr ansmission. We report that nicotine at concentrations between 0.5 and 100 m u M enhanced excitatory synaptic responses and increased the size of the pr esynaptic fiber volley. This effect was reproduced by three neuronal nicoti nic receptor antagonists: dihydro-beta-erythroidine, methyllycaconitine and mecamylamine. In contrast, nicotine, but not nicotinic antagonists, produc ed a dual effect on inhibition: nicotine enhanced gamma-aminobutyric-acid A (GABA(A)) receptor-mediated synaptic responses at low concentration (0.5 m u M) and blocked them at high concentration (100 mu M). We conclude that th e excitatory effects of nicotine are reproduced by nicotinic receptor antag onists, thereby suggesting that these effects might be mediated through rec eptor desensitization, These results also indicate that nicotine differenti ally affects GABAergic inhibition at low and high concentrations-effects th at are not reproduced by antagonists. (C) 1999 Elsevier Science Inc.