title: Comparison of seven different anesthesia protocols for nicotine pharmacologic magnetic resonance imaging in rat.
abstract: Pharmacologic MRI (phMRI) is a non-invasive in vivo imaging method, which can evaluate the drug effects on the brain and provide complementary information to ex vivo techniques. The preclinical phMRI studies usually require anesthesia to reduce the motion and stress of the animals. The anesthesia, however, is a crucial part of the experimental design, as it may modulate the neural drug-induced (de)activation and hemodynamic coupling. Therefore, the aim of the present study was to address this methodologic question by performing phMRI experiments with five anesthetics (α-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane) and seven anesthesia protocols. Nicotine, a widely studied psychostimulant, was administered to rats while measuring blood oxygenation level-dependent (BOLD) signals. Notably different responses were observed depending on the anesthetic used. The highest responses were measured in urethane-anesthetized rats whereas the responses were hardly noticeable in α-chloralose group. As urethane is not commonly used in phMRI, hemodynamic coupling under urethane anesthesia was investigated with functional cerebral blood flow (CBF) and volume-weighted (CBVw) imaging, and simultaneous electrophysiologic and BOLD measurements. The BOLD, CBF, and CBVw measurements in response to nicotine were highly correlated (R(2) ≥ 0.70, p<0.001). BOLD values correlated well (R(2)=0.43, p<10(-6)) with local field potential (LFP) spectral power (13-70Hz) during pharmacologic stimulation. These findings indicate that urethane anesthesia combined with BOLD contrast provides a robust protocol for nicotine phMRI studies. As urethane has mild effects to individual receptor systems, and coupling between electrophysiologic activity and hemodynamic response is maintained, this anesthetic may also be suitable for other phMRI studies.
authors.affiliation: A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Paasonen
authors.affiliation: A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Raimo A
authors.initials: RA
authors.lastname: Salo
authors.affiliation: A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Artem
authors.initials: A
authors.lastname: Shatillo
authors.affiliation: School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Forsberg
authors.affiliation: A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland; VTT Technical Research Centre of Finland, P.O. Box 1199, FI-70211 Kuopio, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Närväinen
authors.affiliation: A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Huttunen
authors.affiliation: A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. Electronic address: olli.grohn@uef.fi.
authors.forename: Olli
authors.initials: O
authors.lastname: Gröhn
mesh_terms: D000818:Animals; D001566:Benzocaine / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D001566:Benzocaine
keywords: Anesthetics; Functional; Magnetic resonance imaging; Nicotine; Pharmacology; Rats