title: Blockade of growth hormone secretagogue receptor 1A signaling by JMV 2959 attenuates the NMDAR antagonist, phencyclidine-induced impairments in prepulse inhibition.
abstract: BACKGROUND
  Schizophrenic-spectrum patients commonly display deficits in preattentive information processing as evidenced, for example, by disrupted prepulse inhibition (PPI), a measure of sensorimotor gating. Similar disruptions in PPI can be induced in rodents and primates by the psychotomimetic drug phencyclidine (PCP), a noncompetitive inhibitor of the NMDA receptor. Mounting evidence suggests that the hunger hormone ghrelin and its constitutively active receptor influences neuronal circuits involved in the regulation of mood and cognition.
  
  
  OBJECTIVE
  In the present series of experiments, we investigated the effects of ghrelin and the growth hormone secretagogue receptor (GHS-R1A) neutral antagonist, JMV 2959, on acoustic startle responses (ASR), PPI, and PCP-induced alterations in PPI.
  
  
  RESULTS
  Intraperitoneal (i.p.) administration of ghrelin (0.033, 0.1, and 0.33 mg/kg) did not alter the ASR or PPI in rats. Conversely, i.p. injection of JMV 2959 (1, 3, and 6 mg/kg), dose dependently decreased the ASR and increased PPI. Pretreatment with JMV 2959 at a dose with no effect on ASR or PPI per se, completely blocked PCP-induced (2 mg/kg) deficits in PPI while pretreatment with the highest dose of ghrelin did not potentiate or alter PPI responses of a sub-threshold dose of PCP (0.75 mg/kg).
  
  
  CONCLUSIONS
  These findings indicate that the GHS-R1A is involved in specific behavioral effects of PCP and may have relevance for patients with schizophrenia.
authors: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 13A, SE-405 30, Gothenburg, Sweden.
authors: Jörgen A
authors: JA
authors: Engel
authors: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 13A, SE-405 30, Gothenburg, Sweden.
authors: Elisabet
authors: E
authors: Jerlhag
authors: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 13A, SE-405 30, Gothenburg, Sweden.
authors: Lennart
authors: L
authors: Svensson
authors: Department of Metabolism and Aging, Scripps Research Institute-Florida, Jupiter, FL, USA.
authors: Roy G
authors: RG
authors: Smith
authors: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 13A, SE-405 30, Gothenburg, Sweden. emil.egecioglu@neuro.gu.se.|Institute of Experimental Medical Sciences, Lund University, Lund, Sweden. emil.egecioglu@neuro.gu.se.
authors: Emil
authors: E
authors: Egecioglu
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D065808:Prepulse Inhibition / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology*
chemical_list: C569751:N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide; D054440:Receptors, Ghrelin; D016194:Receptors, N-Methyl-D-Aspartate; D014230:Triazoles; D010622:Phencyclidine; D005998:Glycine
keywords: Cognition; Dopamine; Glutamate; NMDA