Methamphetamine-induced deficits of brain monoaminergic neuronal markers: distal axotomy or neuronal plasticity
Section snippets
Animal protocol and drug treatment
Adult male Sprague-Dawley rats (225–250 g; Harlan, Indianapolis, IN, USA) were used in all experiments. Animals were individually housed in wire-bottom cages at 22 °C under a 12-h light/dark cycle. METH was dissolved in saline and administered according to the following schedule. Animals were given four i.p. injections of either METH (15 mg/kg as free base) or 0.9% saline vehicle at 2 h intervals. METH was generously supplied and administered to rats in Dr. George Ricaurte's laboratory (Johns
Binding of [3H]-paroxetine to 5-HTT
5-HTT levels were measured using [3H]-paroxetine quantitative autoradiography at 3, 5, and 14 days after METH administration. Due to the widespread distribution of 5-HTT in the CNS, three different levels of the brain were sampled. Brain sections at the level of the striatum, hippocampus and dorsal raphe were selected to examine 5-HTT expression on serotonergic terminal fields and cell bodies. Fig. 1
- ACg
anterior cingulate cortex
- Aq
cerebral aqueduct
- BLA
basal lateral amygdaloid nucleus
- C
control
- CG
Abbreviations used in the figures and tables
Discussion
The major findings of this study are: 1) a METH exposure protocol that produces global and lasting deficits in the levels of the plasma membrane transporters DAT and 5-HTT in the rat brain, fails to produce similar global reductions in VMAT-2 levels or marked activation of microglia and astrocytes. The striatum and central gray are brain regions, among those examined, exhibiting significant deficits in DAT and/or 5-HTT and also in VMAT-2 levels and glial cell activation. However, deficits in
Acknowledgements
This work was supported by grants from the National Institute of Environmental Health Sciences (ES07062 to TRG and NIEHS Center grant ES03819). The authors wish to thank Dr. Jim O'Callaghan for reviewing the manuscript and Dr. Brian Schoefield for assistance with microscopy and imaging.
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