title: Hypocretin/Orexin Peptides Excite Rat Neuroendocrine Dopamine Neurons through Orexin 2 Receptor-Mediated Activation of a Mixed Cation Current.
abstract: Hypocretin/Orexin (H/O) neurons of the lateral hypothalamus are compelling modulator candidates for the chronobiology of neuroendocrine output and, as a consequence, hormone release from the anterior pituitary. Here we investigate the effects of H/O peptides upon tuberoinfundibular dopamine (TIDA) neurons - cells which control, via inhibition, the pituitary secretion of prolactin. In whole cell recordings performed in male rat hypothalamic slices, application of H/O-A, as well as H/O-B, excited oscillating TIDA neurons, inducing a reversible depolarising switch from phasic to tonic discharge. The H/O-induced inward current underpinning this effect was post-synaptic (as it endured in the presence of tetrodotoxin), appeared to be carried by a Na+-dependent transient receptor potential-like channel (as it was blocked by 2-APB and was diminished by removal of extracellular Na+), and was a consequence of OX2R receptor activation (as it was blocked by the OX2R receptor antagonist TCS OX2 29, but not the OX1R receptor antagonist SB 334867). Application of the hormone, melatonin, failed to alter TIDA membrane potential or oscillatory activity. This first description of the electrophysiological effects of H/Os upon the TIDA network identifies cellular mechanisms that may contribute to the circadian rhythmicity of prolactin secretion.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lyons
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arash
authors.initials: A
authors.lastname: Hellysaz
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rachida
authors.initials: R
authors.lastname: Ammari
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Broberger
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002412:Cations / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology; D064446:Orexin Receptors / Q000378:metabolism*; D000068797:Orexins / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D055366:Synaptic Potentials / Q000187:drug effects*; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors
chemical_list: D001896:Boron Compounds; D002412:Cations; D064446:Orexin Receptors; D000068797:Orexins; D050051:Transient Receptor Potential Channels; D012964:Sodium; C109986:2-aminoethoxydiphenyl borate; D008550:Melatonin