Neuronal dysfunction of a long projecting multisynaptic pathway in response to methamphetamine using manganese-enhanced MRI

RationaleManganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) is an emerging in vivo MR approach for pharmacological research. One new application of MEMRI in this area is to characterize functional changes of a specific neural circuit that is essential to the central effects of a drug challenge.ObjectivesTo develop and validate such use of MEMRI in neuropharmacology, the current study applied MEMRI to visualize functional changes within a multisynaptic pathway originating from fasciculus retroflexus (FR) that is central to a commonly abused psychostimulant, methamphetamine (MA).MethodsTwelve rats were injected intraperitoneally with MA (10 mg/kg) or saline every 2 h for a total of four injections. After 6 days, Mn2+ was injected into the habenular nucleus (FR origin) of all animals, and MEMRI was repeatedly performed at certain points in time over 48 h. The evolution of Mn2+-induced signal enhancement was assessed across the FR tract, the ventral tegmental area (VTA), the striatum, the nucleus accumbens, and the prefrontal cortex (PFC), in both MA-injected animals and controls.ResultsMA treatment was found to affect the complexity and efficiency of Mn2+ uptake in the VTA, via the FR tract, with significantly increased Mn2+ accumulation in the VTA, the dorsomedial part of the striatum, and the PFC.ConclusionsMEMRI successfully visualizes disruptions in the multisynaptic pathway as the consequences of repeated MA exposure. MEMRI is potentially an important method in the future to investigate functional changes within a specific pathway under the influences of pharmacological agents, given its excellent functional, in vivo, spatial, and temporal properties.

[1]  J. Gibb,et al.  Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels. , 1976, European journal of pharmacology.

[2]  W. Nauta,et al.  Efferent connections of the habenular nuclei in the rat , 1979, The Journal of comparative neurology.

[3]  H. Lorez,et al.  Fluorescence histochemistry indicates damage of striatal dopamine nerve terminals in rats after multiple doses of methamphetamine. , 1981, Life sciences.

[4]  R. Guillery,et al.  Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain , 1982, Brain Research.

[5]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[6]  J. Raese,et al.  Effects of chronic methamphetamine on the nigral-striatal dopamine system in rat brain: Tyrosine hydroxylase immunochemistry and quantitative light microscopic studies , 1985, Brain Research Bulletin.

[7]  Y. Matsuda,et al.  Action of habenular efferents on ventral tegmental area neurons studied in vitro , 1992, Brain Research Bulletin.

[8]  R. Switzer,et al.  Dissimilar patterns of degeneration in brain following four different addictive stimulants , 1993, Neuroreport.

[9]  G. Ellison.  Stimulant-induced psychosis, the dopamine theory of schizophrenia, and the habenula , 1994, Brain Research Reviews.

[10]  W. Slikker,et al.  Low environmental temperatures or pharmacologic agents that produce hypothermia decrease methamphetamine neurotoxicity in mice , 1994, Brain Research.

[11]  A. Koretsky,et al.  Manganese ion enhances T1‐weighted MRI during brain activation: An approach to direct imaging of brain function , 1997, Magnetic resonance in medicine.

[12]  Afonso C. Silva,et al.  In vivo neuronal tract tracing using manganese‐enhanced magnetic resonance imaging , 1998, Magnetic resonance in medicine.

[13]  Minoru Tsuji,et al.  Differentiation of the Inhibitory Effects of Calcium Antagonists on Abnormal Behaviors Induced by Methamphetamine or Phencyclidine , 1998, Pharmacology.

[14]  H. Ogura,et al.  Peptide N- and P/Q-type Ca2 blockers inhibit stimulant-induced hyperactivity in mice , 1998, Peptides.

[15]  C. Bryant,et al.  Functional Imaging of the Brain in the Evaluation of Drug Response and its Application to the Study of Aging , 1998, Drugs & aging.

[16]  S. Tsai,et al.  Effects of Repeated High-Dose Methamphetamine on Local Cerebral Glucose Utilization in Rats , 1999, Neuropsychopharmacology.

[17]  P. Bordnick,et al.  Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine’s positive subjective effects: a preliminary study , 1999, Psychopharmacology.

[18]  S. C. Licata,et al.  Repeated stimulation of L-type calcium channels in the rat ventral tegmental area mimics the initiation of behavioral sensitization to cocaine , 2000, Psychopharmacology.

[19]  E A Disbrow,et al.  Functional MRI at 1.5 tesla: a comparison of the blood oxygenation level-dependent signal and electrophysiology. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Bankole A Johnson,et al.  Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans , 2000, Neuropsychopharmacology.

[21]  Richard T. Miller,et al.  Neurotoxicity of manganese chloride in neonatal and adult CD rats following subchronic (21‐day) high‐dose oral exposure , 2000, Journal of applied toxicology : JAT.

[22]  M. James,et al.  Pharmacological magnetic resonance imaging: a new application for functional MRI. , 2000, Trends in pharmacological sciences.

[23]  M. Takigawa,et al.  Ca2+ Oscillations in Response to Methamphetamine in Dopamine Neurons of the Ventral Tegmental Area in Rats Subchronically Treated with This Drug , 2000, Annals of the New York Academy of Sciences.

[24]  Ching-Po Lin,et al.  Validation of Diffusion Tensor Magnetic Resonance Axonal Fiber Imaging with Registered Manganese-Enhanced Optic Tracts , 2001, NeuroImage.

[25]  R. Kesner,et al.  Long-term changes in basal ganglia function after a neurotoxic regimen of methamphetamine. , 2001, The Journal of pharmacology and experimental therapeutics.

[26]  J S Fowler,et al.  Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers. , 2001, The American journal of psychiatry.

[27]  G. Ricaurte,et al.  Inhibitors of Na+/H+ and Na+/Ca2+ exchange potentiate methamphetamine‐induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity , 2001, Journal of neurochemistry.

[28]  Marc A Schuckit,et al.  Behavioral and Functional Neuroimaging Evidence for Prefrontal Dysfunction in Methamphetamine-Dependent Subjects , 2002, Neuropsychopharmacology.

[29]  Alan P. Koretsky,et al.  Tracing Odor-Induced Activation in the Olfactory Bulbs of Mice Using Manganese-Enhanced Magnetic Resonance Imaging , 2002, NeuroImage.

[30]  Takashi Ogino,et al.  Detection of hypothalamic activation by manganese ion contrasted T1-weighted magnetic resonance imaging in rats , 2002, Neuroscience Letters.

[31]  D. Heeger,et al.  In this issue , 2002, Nature Reviews Drug Discovery.

[32]  Stephen L. Brown,et al.  Noninvasive Detection of Radiation-Induced Optic Neuropathy by Manganese-Enhanced MRI , 2002, Radiation research.

[33]  M. Verhoye,et al.  In vivo manganese-enhanced magnetic resonance imaging reveals connections and functional properties of the songbird vocal control system , 2002, Neuroscience.

[34]  N. Logothetis,et al.  Magnetic Resonance Imaging of Neuronal Connections in the Macaque Monkey , 2001, Neuron.

[35]  G. Ellison,et al.  Neural degeneration following chronic stimulant abuse reveals a weak link in brain, fasciculus retroflexus, implying the loss of forebrain control circuitry , 2002, European Neuropsychopharmacology.

[36]  Anna Devor,et al.  In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing , 2003, NeuroImage.

[37]  R. Jacobs,et al.  In vivo trans‐synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI) , 2003, Magnetic resonance in medicine.

[38]  M. Verhoye,et al.  In vivo dynamic ME‐MRI reveals differential functional responses of RA‐ and area X‐projecting neurons in the HVC of canaries exposed to conspecific song , 2003, The European journal of neuroscience.

[39]  C. Wiessner,et al.  Three‐dimensional MRI of cerebral projections in rat brain in vivo after intracortical injection of MnCl2 , 2003, NMR in biomedicine.

[40]  T. Nordahl,et al.  Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review. , 2003, The Journal of neuropsychiatry and clinical neurosciences.

[41]  Shoji Naruse,et al.  Detection of the anoxic depolarization of focal ischemia using manganese‐enhanced MRI , 2003, Magnetic resonance in medicine.

[42]  Atsushi Takeda,et al.  Manganese action in brain function , 2003, Brain Research Reviews.

[43]  A. L. Dixon,et al.  Detection of cannabinoid agonist evoked increase in BOLD contrast in rats using functional magnetic resonance imaging , 2004, Neuropharmacology.

[44]  M. Verhoye,et al.  NMR IN BIOMEDICINE NMR Biomed. 2004;17:602–612 Published online in Wiley InterScience (www.interscience.wiley.com). DOI:10.1002/nbm.936 Applications of manganese-enhanced magnetic resonance imaging (MEMRI) to image brain plasticity in song birds , 2022 .

[45]  Ichio Aoki,et al.  In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI , 2004, NeuroImage.

[46]  Afonso C. Silva,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI) , 2004, NMR in biomedicine.

[47]  Yoshimi Anzai,et al.  Statistical mapping of functional olfactory connections of the rat brain in vivo , 2004, NeuroImage.

[48]  E. Bullmore,et al.  Human pharmacological MRI. , 2004, Trends in pharmacological sciences.

[49]  M. Wendland.  Applications of manganese‐enhanced magnetic resonance imaging (MEMRI) to imaging of the heart , 2004, NMR in biomedicine.

[50]  G. Hanson,et al.  The methamphetamine experience: a NIDA partnership , 2004, Neuropharmacology.

[51]  R. Pautler.  In vivo, trans‐synaptic tract‐tracing utilizing manganese‐enhanced magnetic resonance imaging (MEMRI) , 2004, NMR in biomedicine.

[52]  Ichio Aoki,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations , 2004, NMR in biomedicine.

[53]  B. Renaud,et al.  Endogenous Neurotensin in the Ventral Tegmental Area Contributes to Amphetamine Behavioral Sensitization , 2005, Neuropsychopharmacology.

[54]  Annemarie van der Linden,et al.  In vivo MR imaging of the seasonal volumetric and functional plasticity of song control nuclei in relation to song output in a female songbird , 2006, NeuroImage.

[55]  Y. Li,et al.  Dynamic changes in orbitofrontal neuronal activity in rats during opiate administration and withdrawal , 2006, Neuroscience.

[56]  Yoshimi Anzai,et al.  In vivo imaging of functional disruption, recovery and alteration in rat olfactory circuitry after lesion , 2006, NeuroImage.

[57]  Jimmy D Bell,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI) without compromise of the blood–brain barrier detects hypothalamic neuronal activity in vivo , 2006, NMR in biomedicine.

[58]  J. Frahm,et al.  Mapping of the habenulo-interpeduncular pathway in living mice using manganese-enhanced 3D MRI. , 2006, Magnetic Resonance Imaging.

[59]  H. Kauczor,et al.  Manganese‐enhanced magnetic resonance imaging for in vivo assessment of damage and functional improvement following spinal cord injury in mice , 2006, Magnetic resonance in medicine.

[60]  Asla Pitkänen,et al.  Manganese-enhanced magnetic resonance imaging of mossy fiber plasticity in vivo , 2006, NeuroImage.

[61]  Angelo Bifone,et al.  Functional connectivity in the pharmacologically activated brain: Resolving networks of correlated responses to d‐amphetamine , 2007, Magnetic resonance in medicine.

[62]  Robert N. Weinreb,et al.  Magnetic resonance imaging of the visual system in vivo: Transsynaptic illumination of V1 and V2 visual cortex , 2007, NeuroImage.

[63]  Yihong Yang,et al.  Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI) , 2007, Proceedings of the National Academy of Sciences.

[64]  Mathias Hoehn,et al.  Current status of functional MRI on small animals: application to physiology, pathophysiology, and cognition , 2007, NMR in biomedicine.

[65]  Hui Zheng,et al.  In vivo axonal transport rates decrease in a mouse model of Alzheimer's disease , 2007, NeuroImage.

[66]  Angelo Bifone,et al.  In vivo mapping of functional connectivity in neurotransmitter systems using pharmacological MRI , 2007, NeuroImage.

[67]  Rick M. Dijkhuizen,et al.  Changes in neuronal connectivity after stroke in rats as studied by serial manganese-enhanced MRI , 2007, NeuroImage.