Electrophysiological actions of norepinephrine in rat lateral hypothalamus. II. An in vitro study of the effects of iontophoretically applied norepinephrine on LH neuronal responses to γ-aminobutyric acid (GABA)

Jung Tung Cheng, Francis M. Sessler, S. Ausim Azizi, John K. Chapin, Barry D. Waterhouse

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The preceding studies demonstrated that norepinephrine (NE) can consistently augment synaptically mediated (70%) and γ-aminobutyric acid (GABA)-induced (69%) inhibitory responses of lateral hypothalamic (LH) neurons in vivo. The present experiments further characterized the interactions of NE with LH neuronal responses to GABA in terms of α- and ß-receptor mechanisms and demonsrated the utility of the in vitro LH tissue slice preparation as a model for future extra- and intracellular studies of NE modulatory phenomena. Extracellular activity of LH cells was recorded from diencephalic slices (450 μm) incubated in artificial cerebrospinal fluid at 33 °C. Interactions between iontophoretically applied NE, isoproterenol (ISO) or phenylephrine (PE) and responses of LH neurons (n = 64) to GABA microiontophoresis were quantitated and characterized using computer-generated ratemeter and histogram records. This analysis revealed two distinct actions of NE on GABA-induced responses of LH neurons. In 8 of 32 cells tested (25%), locally applied NE markedly enhanced inhibitory responses to GABA iontophoresis in a manner identical to that observed in vivo. However, in 20 cells (62.5%), iontophoretic application of NE produced a clear antagonism of GABA responses. NE also exerted dual effects on the background firing rate of LH neurons, causing both inhibition and excitation. Overall, in those cells where NE administration increased spontaneous discharge, it either antagonized or had no effect on GABA-mediated inhibition. In contrast, spontaneous firing rate was never elevated above control levels in those cases where NE potentiated GABA responses. Additional experiments demonstrated that the GABA potentiating actions of the benzodiazepine, flurazepam, were preserved in LH tissue slice preparations. In addition, iontophoretic application of the ß-agonist, ISO, routinely suppressed the spontaneous activity of LH neurons and mimicked the facilitating action of NE on GABA. Likewise, microiontophoretic application of 8-bromo cyclic adenosine monophosphate (AMP) enhanced GABA-induced inhibition of LH firing rate in each of 11 cells tested. On the other hand, local administration of the alpha agonist, PE, routinely produced NE-like antagonism of GABA inhibition along with increases in spontaneous firing rate. Taken together these findings indicate that the commonly observed in vivo phenomena of NE augmentation of GABA and suppression of LH neuron spontaneous firing can be demonstrated in vitro, and most likely result from activation of beta adrenoceptors and subsequent elevation of cyclic AMP levels. As such these results suggest that the in vitro preparation will be a useful tool for further investigation of the transmembrane and intracellular events associated with noradrenergically mediated enhancement of GABA. However, in contrast to results obtained in vivo, NE antagonism of GABA inhibition and excitatory effects on spontaneous activity were more frequently observed in LH slices and appear to be mediated by alpha receptor activation. The reduced capacity of NE to augment GABA in vitro might be related to changes in the balance between α- and ß-mediated effects rather than deficits in GABA-facilitating mechanisms, since ISO, cyclic AMP and the benzodiazepine were all routinely capable of enhancing GABAergic responses.

Original languageEnglish (US)
Pages (from-to)90-105
Number of pages16
JournalBrain Research
Issue number1
StatePublished - Apr 12 1988
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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