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

Psychopharmacology (Berl). 2008 Mar;196(4):543-53. doi: 10.1007/s00213-007-0990-x. Epub 2007 Nov 14.


Rationale: Manganese (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.

Objectives: To 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).

Methods: Twelve 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.

Results: MA 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.

Conclusions: MEMRI 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cations, Divalent
  • Central Nervous System Stimulants / pharmacology*
  • Contrast Media
  • Corpus Striatum / pathology
  • Habenula / metabolism
  • Image Enhancement / methods
  • Magnetic Resonance Imaging
  • Male
  • Manganese / pharmacokinetics*
  • Methamphetamine / pharmacology*
  • Neural Pathways / drug effects*
  • Neural Pathways / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neurotoxicity Syndromes / metabolism*
  • Neurotoxicity Syndromes / pathology
  • Nucleus Accumbens / metabolism
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / metabolism
  • Ventral Tegmental Area / metabolism


  • Cations, Divalent
  • Central Nervous System Stimulants
  • Contrast Media
  • Manganese
  • Methamphetamine