Effects of various neuroactive substances on single-unit activities of hypothalamic arcuate neurons in brain slices

Extracellular single-unit activities of 288 dorsomedial/ventrolateral hypothalamic arcuate (ARC) neurons were studied electrophysiologically in brain slices in vitro. We tested the effects of several neuroactive substances plus some of their analogs in this study. Among them, baclofen, a GABAb-receptor agonist, inhibited 95.6% of ARC neurons tested, although GABA itself was much less effective (23.8%). About half of baclofen's effect was blocked by phaclofen, a GABAB antagonist. Serotonin and dopamine also exhibited mostly inhibitory effects on responsive ARC neurons (80 and 78.4%, respectively), although more than half ARC neurons tested (53.3% of 169) were not responsive to dopamine. Neither ketanserin, a 5-HT2, nor domperidone, a D2 receptor antagonist, had much effect on blocking the actions of 5-HT or DA. Histamine and carbachol excited 67.4% and 52.2% of ARC neurons tested, respectively. Moreover, their effects were completely blocked by pyrilamine, a H1, and atropine, a muscarinic receptor antagonist, respectively. Ranitidine, a H2 receptor antagonist, however, was less effective. Norepinephrine had about equal number of excitation (33.3%) and inhibition (38.5%) on ARC neurons. Cholecystokinin-octapeptide sulphate (CCK-8S), a neuropeptide tested exerted potent excitatory effects on ARC neurons (62.8% of 137). In summary, ARC neurons in a more localized region aiming at the tuberoinfundibular dopaminergic neurons were selected in this study. Their responses to many agents and the implications on the regulation of prolactin secretion were discussed.