In vivo modulation of post-spike excitability in vasopressin cells by kappa-opioid receptor activation

An endogenous kappa-opioid agonist reduces the duration of phasic bursts in vasopressin cells. Non-synaptic post-spike depolarizing after-potentials u nderlie activity during bursts by increasing post-spike excitability and ka ppa-receptor activation reduces depolarizing after-potential amplitude in v itro. To investigate the effects of kappa-opioids on post-spike excitabilit y in vivo, we analysed extracellular recordings of the spontaneous activity of identified supraoptic nucleus vasopressin cells in urethane-anaesthetiz ed rats infused with Ringer's solution (n = 17) or the kappa-agonist, U50,4 88H (2.5 mu g/h at 0.5 mu l/h; n = 23), into the supraoptic nucleus over 5 days. We plotted the mean hazard function for the interspike interval distr ibutions as a measure of the post-spike excitability of these cells. Follow ing each spike, the probability of another spike firing in vasopressin cell s recorded from U50,488H infused nuclei was markedly reduced compared to Ri nger's treated vasopressin cells. To determine whether U50,488H could reduc e post-spike excitability in cells that displayed spontaneous phasic activi ty, we infused U50,488H (50 mu g/h at 1 mu l/h, i.c.v.), for 1-12 h while r ecording vasopressin cell activity. Nine of 10 vasopressin cells were silen ced by i.c.v. U50,488H 15 +/- 5 min into the infusion. Six cells exhibited spontaneous phasic activity before U50,488H infusion and recordings from th ree of these phasic cells were maintained until activity recovered; during U50,488H infusion, the activity of these three cells was irregular. Generat ion of the mean hazard function before and during U50,488H infusion reveale d a reduction in post-spike excitability during U50,488H infusion. Thus, ka ppa-receptor activation reduces post-spike excitability in vivo; this may r eflect inhibition of depolarizing after-potentials and may thus underlie th e reduction in burst duration of vasopressin cells caused by an endogenous kappa-agonist in vivo.