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


OBJECTIVE
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.
Hsu
Yi-Hua
YH
Functional and Micro-Magnetic Resonance Imaging Center, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, Republic of China.
Chen
Chiao-Chi V
CC
Zechariah
Anil
A
Yen
Cecil C
CC
Yang
Li-Chuan
LC
Chang
Chen
C
D000818:Animals; D002413:Cations, Divalent; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003287:Contrast Media; D003342:Corpus Striatum / Q000473:pathology; D019262:Habenula / Q000378:metabolism; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics*; D008694:Methamphetamine / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology; D009714:Nucleus Accumbens / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism
D002413:Cations, Divalent; D000697:Central Nervous System Stimulants; D003287:Contrast Media; D008345:Manganese; D008694:Methamphetamine