HISTAMINE MEDIATES FAST SYNAPTIC INHIBITION OF RAT SUPRAOPTIC OXYTOCIN NEURONS VIA CHLORIDE CONDUCTANCE ACTIVATION

Axons from the histaminergic neurons of the tuberomammillary nucleus p roject to both the anterior and tuberal portions of the supraoptic nuc leus. Histamine is known to activate vasopressin neurons via a histami ne receptor subtype I and to increase release of vasopressin, but effe cts on oxytocin neurons have been previously unexplored. Here we inves tigated the effects of tuberomammillary nucleus electrical stimulation as well as of histamine antagonists on supraoptic nucleus oxytocin an d vasopressin neurons in slices of rat hypothalamus. Electrical stimul ation evoked short constant latency (similar to 5 ms), fast (4-6 ms on set to peak) inhibitory postsynaptic potentials in oxytocin neurons an d, as shown previously fast excitatory postsynaptic potentials in vaso pressin neurons. These synaptic responses followed paired-pulse stimul us frequencies up to 100 Hz and were, thus, probably reflecting monosy naptic connections. Inhibitory postsynaptic potentials were selectivel y blocked by histamine receptor subtype 2 antagonists (either cimetidi ne or famotidine) and by picrotoxin but not by histamine receptor subt ype 1 antagonists or bicuculline. Similar synaptic responses to tubero mammillary nucleus stimulation were found in 16 of 16 neurons immunocy tochemically identified as oxytocinergic and in seven putative oxytoci n neurons. Perifusion of the slice with low chloride medium (4.8 mM) r eversed stimulus-evoked inhibitory postsynaptic potentials. We conclud e that histaminergic neurons monosynaptically contact both oxytocin an d vasopressin cells of the supraoptic nucleus and inhibit the former v ia activation of chloride channels which can be blocked by the histami ne receptor subtype 2 antagonists, famotidine and cimetidine.