Vasopressin increases GABAergic inhibition of rat hypothalamic paraventricular nucleus neurons in vitro

This investigation used an in vitro hypothalamic brain slice preparation an d whole cell and perforated-patch recording to examine the response of magn ocellular neurons in hypothalamic paraventricular nucleus (PVN) to bath app lications of vasopressin (VP; 100-500 nM). in 22/38 cells, responses were c haracterized by an increase in the frequency of bicuculline-sensitive inhib itory postsynaptic potentials or currents with no detectable influence on e xcitatory postsynaptic events. Perforated-patch recordings confirmed that V P did not have an effect on intrinsic membrane properties of magnocellular PVN neurons (n = 17). Analysis of intrinsic membrane properties obtained wi th perforated-patch recording (n = 23) demonstrated that all of nine VP-sen sitive neurons showed a rebound depolarization after transient membrane hyp erpolarization from rest. By contrast, 12/14 nonresponding neurons displaye d a delayed return to resting membrane potentials. Recordings of reversed i nhibitory postsynaptic currents with chloride-loaded electrodes showed that responses to VP persisted in media containing glutamate receptor antagonis ts but were abolished in the presence of tetrodotoxin. in addition, respons es were mimicked by vasotocin [Phe(2), Orn(8)], a selective V-1a receptor a gonist, and blocked by [beta-Mercapto- beta,beta-cyclopentamethylenepropion yl(1),O-Me-Tyr(2), Arg(8)]-VP (Manning compound), a V-1a/OT receptor antago nist. Neither [deamino-Cys(1),Val(4),D-Arg(8)]-VP, a selective V-2 receptor agonist, nor oxytocin were effective. Collectively, the results imply that VP acts at V-1a receptors to excite GABAergic neurons that are presynaptic to a population of magnocellular PVN neurons the identity of which feature s a unique redound depolarization. Endogenous sources of VP may be VP-synth esizing neurons in suprachiasmatic nucleus, known to project toward the per inuclear regions of PVN, and/or the magnocellular neurons within PVN.