title: Antidepressant activity of nociceptin/orphanin FQ receptor antagonists in the mouse learned helplessness.
abstract: Pharmacological and genetic evidence support antidepressant-like effects elicited by the blockade of the NOP receptor. The learned helplessness (LH) model employs uncontrollable and unpredictable electric footshocks as a stressor stimulus to induce a depressive-like phenotype that can be reversed by classical antidepressants.
  
  
  
  The present study aimed to evaluate the action of NOP receptor antagonists in helpless mice.
  
  
  
  Male Swiss mice were subjected to the three steps of the LH paradigm (i.e., (1) induction, (2) screening, and (3) test). Only helpless animals were subjected to the test session. During the test session, animals were placed in the electrified chamber and the latency to escape after the footshock and the frequency of escape failures were recorded. The effect of the following treatments administered before the test session were evaluated: nortriptyline (30 mg/kg, ip, 60 min), fluoxetine (30 mg/kg, ip, four consecutive days of treatment), and NOP antagonists SB-612111 (1-10 mg/kg, ip, 30 min) and UFP-101 (1-10 nmol, icv, 5 min). To rule out possible biases, the effects of treatments on controllable stressful and non stressful situations were assessed.
  
  
  
  In helpless mice, nortriptyline, fluoxetine, UFP-101 (3-10 nmol), and SB-612111 (3-10 mg/kg) significantly reduced escape latencies and escape failures. No effects of drug treatments were observed in mice subjected to the controllable electric footshocks and non stressful situations.
  
  
  
  Acute treatment with NOP antagonists reversed helplessness similarly to the classical antidepressants. These findings support the proposal that NOP receptor antagonists are worthy of development as innovative antidepressant drugs.
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Campus Universitário, Lagoa Nova, Natal, Brazil, 59072-970.
authors.forename: Victor A D
authors.initials: VA
authors.lastname: Holanda
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Campus Universitário, Lagoa Nova, Natal, Brazil, 59072-970.
authors.forename: Iris U
authors.initials: IU
authors.lastname: Medeiros
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Campus Universitário, Lagoa Nova, Natal, Brazil, 59072-970.
authors.forename: Laila
authors.initials: L
authors.lastname: Asth
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Campus Universitário, Lagoa Nova, Natal, Brazil, 59072-970. egavioli@hotmail.com.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003508:Cycloheptanes / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology*; D006380:Helplessness, Learned; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009661:Nortriptyline / Q000494:pharmacology*; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011957:Receptors, Opioid; D015398:Signal Transduction / Q000187:drug effects; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000928:Antidepressive Agents; D003508:Cycloheptanes; D005473:Fluoxetine; D009292:Narcotic Antagonists; D009661:Nortriptyline; D018847:Opioid Peptides; D010880:Piperidines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C482404:cis-1-methyl-7-((4-(2,6-dichlorophenyl)piperidin-1-yl)methyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol; C000722287:Oprl1 protein, mouse
keywords: Antidepressants; LH model; Mouse; NOP receptor; SB-612111; UFP-101; Uncontrollable stress