Article

Neurotoxic (+)-methamphetamine treatment in rats increases brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) expression in multiple brain regions

Division of Neurology, Department of Pediatrics, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Neuroscience (Impact Factor: 3.36). 03/2011; 184:164-71. DOI: 10.1016/j.neuroscience.2011.03.045
Source: PubMed

ABSTRACT

Methamphetamine (MA) is an abused stimulant which can result in cognitive deficits and monoamine depletions. Animal models of neurotoxic MA exposure show reductions in dopamine, serotonin, and their associated transporters. MA abuse can result in long-term attention, working memory, and executive function deficits in humans and deficits in route-based egocentric learning, novel object recognition, and novel odor preference in rodents. MA has also been shown to affect brain-derived neurotrophic factor (BDNF) in humans and rodents. This experiment examined the effects of a MA binge dosing regimen (10 mg/kg x 4 at 2 h intervals, s.c.) in Sprague-Dawley rats on BDNF, tropomyosin receptor kinase B (TrkB), and tyrosine hydroxylase (TH) mRNA expression, and plasma corticosterone. Tissues were collected 1, 7, and 24 h following the last MA dose. Expression of BDNF and TrkB mRNA was analyzed using in situ hybridization with cRNA probes. Frontal, parietal, and entorhinal cortical BDNF mRNA expression were increased by MA exposure at all time-points. Increases in BDNF mRNA were also seen in the hippocampal CA1, prefrontal cortex (PFC), piriform cortex, and locus coeruleus but only at specific times. TrkB mRNA expression was modified in several subregions of the hippocampus as well as in PFC and striatum. TH mRNA was increased at the 1 h time-point in the substantia nigra pars compacta with no differences noted at the other times. Corticosterone levels were increased at all three time-points. The findings suggest that BDNF and its receptor may be upregulated as a compensatory mechanism after MA exposure.

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    • "Prior preclinical studies have supported this explanation (Pu and Vorhees, 1993;Asanuma et al., 2004;LaVoie et al., 2004). Another potential response to MA neurotoxicity is an upregulation of brain-derived neurotrophic factor (BDNF) levels, as has been previously reported in humans (Kim et al., 2005) and rodents (Braun et al., 2011). Due to its involvement in neuronal growth, maintenance and survival (specifically of dopaminergic neurons (Hyman et al., 1991)), BDNF may produce a neuroprotective mechanism against MA (Matsuzaki et al., 2004), and may thus contribute to the observed morphological abnormalities in MA-dependent individuals. "
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