title: Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats.
abstract: Depression is one of the most common psychiatric disorders in the world; however, its mechanisms remain unclear. Recently, a new signal-transduction pathway, namely Rho/Rho-kinase signalling, has been suggested to be involved in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However there is no evidence showing the involvement of Rho-kinase pathway in depression. In addition, the infralimbic cortex, rodent equivalent to subgenual cingulate cortex has been shown to be responsible for emotional responses. Thus, in the present study, intracranial guide cannulae were stereotaxically implanted bilaterally into the infralimbic cortex, and the effects of repeated microinjections of a Rho-kinase (ROCK) inhibitor Y-27632 (10 nmol) were investigated in rats. Y-27632 significantly decreased immobility time and increased swimming and climbing behaviors when compared to fluoxetine (10 μg) and saline groups in the forced swim test. In addition, Y-27632 treatment did not affect spontaneous locomotor activity and forelimb use in the open-field and cylinder tests respectively; but it enhanced limb placing accuracy in the ladder rung walking test. Our results suggest that Y-27632 could be a potentially active antidepressant agent.
authors.affiliation: Department of Pharmacology, Meram Faculty of Medicine, University of Konya-NE, Konya, Turkey. Electronic address: salim.inan@gmail.com.
authors.forename: Salim Yalcin
authors.initials: SY
authors.lastname: Inan
authors.affiliation: Department of Pharmacology, Meram Faculty of Medicine, University of Konya-NE, Konya, Turkey.
authors.forename: Burak Cem
authors.initials: BC
authors.lastname: Soner
authors.affiliation: Department of Pharmacology, Meram Faculty of Medicine, University of Konya-NE, Konya, Turkey.
authors.forename: Ayse Saide
authors.initials: AS
authors.lastname: Sahin
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008845:Microinjections; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D000928:Antidepressive Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases
keywords: Behavior; Depression; Infralimbic cortex; Rho-kinase; Y-27632