title: Neuronal effects of a nickel-piperazine/NO donor complex in rodents.
abstract: In the brain, NO is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also importantly involved in many neuronal functions and innumerable roles of NO in many brain related disorders including epilepsy, schizophrenia, drug addiction, anxiety, major depression, have been postulated. The present study aimed to explore the neuronal role exerted by the metal-nonoate compound Ni(PipNONO)Cl, a novel NO donor whose vascular protective effects have been recently demonstrated. Ni(PipNONO)Cl showed antidepressant-like properties in the tail suspension test and antiamnesic activity in the passive avoidance test in the absence of any hypernociceptive response to a mechanical stimulus. These effects were related to the NO-releasing properties of the compound within the central nervous system as demonstrated by the increase of iNOS levels in the brain, spinal cord and dura mater. The modulation of neuronal functions appeared after acute and repeated treatment, showing the lack of any tolerance to neuronal effects. At the dose used (10 mg/kg i.p.), Ni(PipNONO)Cl did not induce any visible sign of toxicity and experiments were performed in the absence of locomotor impairments. In addition to the NO-related neuronal activities of Ni(PipNONO)Cl, the decomposition control compound Ni(Pip)Cl2 showed anxiogenic-like and procognitive effects. The present findings showed neuronal modulatory activity of Ni(PipNONO)Cl through a NO-mediated mechanism. The activities of the decomposition compound Ni(Pip)Cl2 attributed to Ni(PipNONO)Cl the capability to modulate additional neuronal functions independently from NO releasing properties extending and improving the therapeutic perspectives of the NO donor.
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Sanna
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 2, 53100 Siena, Italy; Noxamet Ltd, Via Besana 2, 20122 Milano, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Monti
authors.affiliation: Noxamet Ltd, Via Besana 2, 20122 Milano, Italy; Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Casella
authors.affiliation: Noxamet Ltd, Via Besana 2, 20122 Milano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Roggeri
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. Electronic address: nicoletta.galeotti@unifi.it.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Galeotti
authors.affiliation: Department of Life Sciences, University of Siena, Via A. Moro 2, 53100 Siena, Italy; Noxamet Ltd, Via Besana 2, 20122 Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Morbidelli
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage; D000928:Antidepressive Agents / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009532:Nickel / Q000008:administration & dosage*; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D020030:Nitric Oxide Donors; D010879:Piperazines; D009532:Nickel; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051744:Protein Kinase C-epsilon
keywords: Anxiety; Central nervous system; Depression; Locomotor behavior; Memory; Nitric oxide