Responses of ventromedial hypothalamic neurons in vitro to norepinephrine: dependence on dose and receptor type.

Application of norepinephrine (NE) at 12.5 microM in the bath surrounding hypothalamic slices from ovariectomized rats could evoke excitation, inhibition, or biphasic inhibition-excitation from single neurons in the ventromedial nucleus. Whether the rats were treated with estrogen or not did not alter the distribution of the type of neuronal responses to NE in vitro. Altering the composition of the bathing solution to achieve synaptic blockade did not abolish or alter the type of responses, indicating that all these types of NE responses, including both phases of the biphasic response, were mediated by postsynaptic receptors. Experiments with varying doses of NE showed that the inhibitory response could be evoked at doses lower than those required to evoke the excitatory response. The effective dose for 50% of the responsive neurons (ED50) was lower than 1.25 microM for inhibitions and higher than 5 microM for excitations. Using specific adrenergic receptor agonists and antagonists, it was found that the excitation and the inhibition were mediated, primarily, by alpha 1- and alpha 2-receptors, respectively. beta-Receptors played only a minor role, but might be related to both excitation and inhibition. Study with adrenergic agents further revealed that different types of adrenergic receptors co-localized not only in neurons showing the biphasic response, but also in a major portion of neurons showing monophasic excitation or inhibition. Because of the co-localization and the differential sensitivities to NE, alteration of the dose of NE or the ratio of excitatory/inhibitor receptors co-localized on a neuron should be able to reverse the type of a neuronal response to NE.