Alpha-adrenergic activation of rat hypothalamic supraoptic neurons maintained in vitro

Extracellular recordings from 141 rat supraoptic nucleus neurons maintained in vitro in a perfused hypothalamic explant indicated that the excitability of 85% of cells was enhanced by the addition of 10-200 microM norepinephrine (NE) and the alpha-agonist methoxamine (MOXY), but not by isoproterenol, to the perfusion medium or by pressure application. Similar responses were observed from 7 cells maintained in synaptic isolation in medium containing 15 mM Mg2+. At the lowest effective concentration (10 microM), NE and MOXY induced bursting activity without an overall increase in firing frequency; at higher concentrations an initial increase in firing frequency was followed by the appearance of phasic activity patterns. The actions of NE and MOXY were reversibly blocked by administration of the alpha-adrenergic antagonists phenoxybenzamine (1-10 microM), yohimbine (greater than 10 microM) and irreversibly blocked by prazosin (10 nM-1 microM). These observations suggest that NE has a predominantly facilitatory role to enhance the excitability and promote bursting activity in supraoptic neurosecretory neurons through an alpha-1 adrenoreceptor mechanism.