Excitation of neurones in the rat paraventricular nucleus in vitro by vasopressin and oxytocin.

Extracellular recordings were made from ninety-seven spontaneously firing cells in the paraventricular nucleus (p.v.n.) of the rat hypothalamic slice preparation. The spontaneously firing cells tested fired at 0.1-8 spikes/s but the majority showed a slow irregular firing pattern. The average firing rate of all ninety-seven cells was 2.2 +/- 0.2 spikes/s (mean +/- S.E. of mean). Six cells showed a phasic firing pattern. Following bath application of arginine-vasopressin (AVP) 10(-7) M, sixty-four (66%) of ninety-seven p.v.n. cells showed excitatory responses and three (3%) cells inhibitory responses. Bath application of oxytocin (OXT) 10(-7) M excited thirty-nine (57%) of sixty-eight p.v.n. cells and inhibited two (3%) cells. Individual p.v.n. cells responded to application of both AVP and OXT, but the magnitude and threshold of the responses varied from cell to cell. Of the sixty-six cells tested with both peptides at 10(-7) M, sixteen showed similar responses to both and fifteen showed no response to either: twenty cells showed a greater response to AVP and fifteen a greater response to OXT. Of six phasic firing cells, two showed excitatory responses to AVP and all four cells tested did not show any response to OXT. The dose-dependence of the response to AVP and OXT was tested in six p.v.n. cells. There was a direct relationship between peptide concentration and increased firing rate. The threshold concentration of the peptides ranged from 10(-8) to 10(-10) M. The cells responsive to the peptides were not located in particular areas of the p.v.n. but were diffusely distributed throughout the nucleus. After blocking synaptic transmission with a low Ca2+ and high Mg2+ medium, all tested cells (AVP, n = 15; OXT, n = 14) which had responded to applications of AVP or OXT in normal medium still showed responses to the peptides, although the effect was less marked in half the cells. However, in the absence of synaptic transmission two cells showed unimpaired responses to one of the peptides but greatly depressed responses to the other. The V1-receptor antagonist [1-(beta-mercapto-, beta-cyclopentamethylenepropionic acid)], 8-D-arginine-vasopressin (d(CH2)5DAVP) or V1/V2-receptor antagonist [1-(beta-mercapto-, beta-cyclopentamethylenepropionic acid), 2-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-TyrVAVP) completely or partly blocked the AVP-induced responses, while the V2-receptor agonist 1-deamino-8-D-arginine-vasopressin (dDAVP) did not influence the spontaneous discharges of the cells.(ABSTRACT TRUNCATED AT 400 WORDS)