title: Functional magnetic resonance mapping of intracerebroventricular infusion of a neuroactive peptide in the anaesthetised rat.
abstract: Pharmacological magnetic resonance imaging (phMRI) methods map the cerebral haemodynamic response to challenge with psychotropic agents as a surrogate for drug-induced changes in brain activity. However, many neuroactive compounds present low blood-brain barrier penetration and thus systemic administration may result in insufficient brain concentration. Intracerebroventricular (ICV) administration has been long used as an effective way of bypassing the blood-brain barrier in studies with non-brain-penetrant compounds, such as neuropeptides. In order to extend the range of pharmacological substances accessible to phMRI, we have developed methods to map relative cerebral blood volume (rCBV) changes induced by in situ ICV administration of neuroactive agents in the anaesthetised rat. We have applied this method to study for the first time the phMRI response to central administration of a neuropeptide, the metabolically stable and potent NK1 receptor agonist GR-73632. ICV administration of 4.2 pmol of GR-73632 produced a rapid onset and sustained rCBV increase in several brain structures, such as the amygdala, the caudate putamen and the cortex. These results demonstrate the feasibility of phMRI as a tool to study the functional correlates of brain activity induced by central administration of neuroactive agents.
authors.affiliation: Department of Neuroimaging, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. alessandro.2.gozzi@gsk.com
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzi
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.forename: Torsten
authors.initials: T
authors.lastname: Reese
authors.forename: Valerio
authors.initials: V
authors.lastname: Crestan
authors.forename: Simone
authors.initials: S
authors.lastname: Bertani
authors.forename: Giuliano
authors.initials: G
authors.lastname: Turrini
authors.forename: Mauro
authors.initials: M
authors.lastname: Corsi
authors.forename: Angelo
authors.initials: A
authors.lastname: Bifone
mesh_terms: D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping / Q000295:instrumentation / Q000379:methods; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D007276:Injections, Intraventricular; D020547:Lateral Ventricles / Q000601:surgery; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009480:Neuropharmacology / Q000295:instrumentation / Q000379:methods*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000777:Anesthetics; D009479:Neuropeptides; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; C068032:GR 73632; D013373:Substance P