Iontophoretic application of glucocorticoids inhibits identified neurones in the rat paraventricular nucleus

Abstract

In an electrophysiological study designed to examine the negative feedback effects of glucocorticoid hormones, we have recorded the electrical activity of 147 neurones in the paraventricular nucleus of the rat hypothalamus. 37 (25%) of the neurones were antidromically identified as projecting to the median eminence and were located at a mean depth of 2.35 +/- 0.08 mm from the base of the brain, corresponding with the corticotropin-releasing factor-rich region of the nucleus. The mean firing rate of the identified cells was 4.7 +/- 0.6 Hz which was not significantly different from that of adjacent, unidentified cells (5.6 +/- 0.6 Hz). Most (17/18, 94%) of these cells tested responded to painful somatosensory stimuli and 26 (74%) of the identified cells were inhibited by iontophoretic application of corticosterone and/or hydrocortisone, whereas only one cell was excited and 8 unaffected. Of the identified cells, only 18 (20%) were inhibited, 36 (41%) were excited and 34 (39%) were non-responsive. The proportion of inhibitory responses was thus greater for the identified cells (P less than 0.005; chi 2-test). For the identified cells, whose spontaneous activity was unaffected by glucocorticoid application, glutamate-evoked responses could usually be depressed by the application. The time course of all responses usually showed an immediate onset, increasing in magnitude and continuing for extended periods following cessation of iontophoresis. Electrophysiologically identified magnocellular neurones were also tested and the majority (7/12, 58%) of vasopressin-secreting neurons were also found to be inhibited, whilst all (8/8, 100%) of the oxytocin-secreting neurones were excited by the glucocorticoid application. These results may represent an electrophysiological correlate of the negative feedback control of adrenocortical secretion and are discussed within this context.