title: Differential effects of hypocretins on noise-alone versus potentiated startle responses.
abstract: Hypocretins are recently discovered neuropeptides, synthesized exclusively in the hypothalamus with excitatory efferents to noradrenergic, serotonergic, and GABAergic (gamma-aminobutyric acid) neurons. Hypocretins also increase corticotropin releasing hormone (CRH) secretion. These actions suggest a possible role for hypocretins in the neurobiology of anxiety, fear, or startle mechanisms. We examined the effects of intracerebroventricular (ICV) administration of hypocretin-A and hypocretin-B on behavior in the Startle Potentiated Startle (SPS) paradigm, a repeated measures, non-shock animal model for studying the classically conditioned enhancement of acoustic startle in the rat. SPS has been used to study effects of anxiolytic treatments. Male Sprague-Dawley rats were tested using the SPS paradigm for 3 days (M-W-F). Following training, rats were anesthetized and 26 gauge stainless cannulae were permanently implanted into the lateral ventricle for intracerebroventricular (ICV) infusions. Following 6-9 days of recovery period, the M-W-F SPS testing was resumed. ICV infusion of both Hypocretin-A (1 and 3 nM) and Hypocretin-B (3 and 10 nM) produced significant reduction in Noise Alone Startle amplitude compared to pre-infusion baseline, whereas infusion with vehicle did not affect Noise Alone Startle. The effect of Hypocretin-B was brief (first 10 min post-infusion), whereas the effect of Hypocretin-A persisted across much of the 50 min post-infusion period. Neither Hypocretin-A nor Hypocretin-B significantly altered the magnitude of the SPS response. Contrary to our expectations, hypocretins seems to possess anxiolytic rather than pro-anxiogenic properties, as indicated by decrease in Noise Alone Startle.
authors.affiliation: Department of Psychiatry (H073), USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Singareddy
authors.forename: Thomas
authors.initials: T
authors.lastname: Uhde
authors.forename: Randall
authors.initials: R
authors.lastname: Commissaris
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009622:Noise; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012022:Reflex, Acoustic / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013566:Sympathomimetics / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D013566:Sympathomimetics