title: A robust experimental protocol for pharmacological fMRI in rats and mice.
abstract: Pharmacological Magnetic Resonance Imaging (phMRI) methods have significantly expanded the stimulation repertoire available to preclinical fMRI research, by allowing to selectively probe the activity of specific brain circuitries and neurotransmitter systems. However, the application of phMRI to animal models is constrained by a number of experimental factors. Firstly, in order to prevent motion artefacts and reduce restraint-induced stress, phMRI studies are typically performed under anaesthesia. Moreover, several psychoactive drugs produce blood pressure changes and alterations in respiratory frequency that may perturb central haemodynamic readouts of brain function. Hence, the quality and outcome of phMRI studies is critically dependent on the ability to monitor and control peripheral physiological parameters (i.e. blood pressure, arterial blood gases) that could alter phMRI readouts. Here we provide a thorough methodological description of a robust protocol to measure drug-induced cerebral blood volume changes in anaesthetised rats and mice. We show that the protocol ensures stable physiological parameters and robust phMRI response to the psychostimulant drug d-amphetamine in three different rat strains. We also document the successful application of the protocol to map the central effects produced by d-amphetamine in C57Bl/6J mice, a strain commonly used as background for the generation of transgenic lines, thus paving the way to the implementation of phMRI in genetically engineered animals.
authors: GlaxoSmithKline Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy.
authors: Livia
authors: L
authors: Ferrari
authors: GlaxoSmithKline Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy.
authors: Giuliano
authors: G
authors: Turrini
authors: GlaxoSmithKline Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy.
authors: Valerio
authors: V
authors: Crestan
authors: GlaxoSmithKline Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy.
authors: Simone
authors: S
authors: Bertani
authors: GlaxoSmithKline Pathology Department, SA Ware, Hertford, UK.
authors: Patrizia
authors: P
authors: Cristofori
authors: Centre for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa, Italy.
authors: Angelo
authors: A
authors: Bifone
authors: Centre for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127 Pisa, Italy. Electronic address: alessandro.gozzi@iit.it.
authors: Alessandro
authors: A
authors: Gozzi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine