Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats.
BACKGROUND
Methamphetamine (MA) use is a worldwide problem. Abusers can have cognitive deficits, monoamine reductions, and altered magnetic resonance spectroscopy findings. Animal models have been used to investigate some of these effects, however many of these experiments have not examined the impact of MA on the stress response. For example, numerous studies have demonstrated (+)-MA-induced neurotoxicity and monoamine reductions, however the effects of MA on other markers that may play a role in neurotoxicity or cell energetics such as glucose, corticosterone, and/or creatine have received less attention. In this experiment, the effects of a neurotoxic regimen of (+)-MA (4 doses at 2 h intervals) on brain monoamines, neostriatal GFAP, plasma corticosterone, creatinine, and glucose, and brain and muscle creatine were evaluated 1, 7, 24, and 72 h after the first dose. In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session) 4 times at 2 h intervals].


RESULTS
MA increased corticosterone from 1-72 h with a peak 1 h after the first treatment, whereas glucose was only increased 1 h post-treatment. Neostriatal and hippocampal monoamines were decreased at 7, 24, and 72 h, with a concurrent increase in GFAP at 72 h. There was no effect of MA on regional brain creatine, however plasma creatinine was increased during the first 24 h and decreased by 72 h. As with MA treatment, forced swim increased corticosterone more than MA initially. Unlike MA, forced swim reduced creatine in the cerebellum with no change in other brain regions while plasma creatinine was decreased at 1 and 7 h. Glucose in plasma was decreased at 7 h.


CONCLUSIONS
Both MA and forced swim increase demand on energy substrates but in different ways, and MA has persistent effects on corticosterone that are not attributable to stress alone.
Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. nicole.r.herring@vanderbilt.edu
Nicole R
NR
Herring
Tori L
TL
Schaefer
Peter H
PH
Tang
Matthew R
MR
Skelton
James P
JP
Lucot
Gary A
GA
Gudelsky
Charles V
CV
Vorhees
Michael T
MT
Williams
D000311:Adrenal Glands / Q000033:anatomy & histology; D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism*; D001831:Body Temperature / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D003401:Creatine / Q000097:blood*; D003404:Creatinine / Q000097:blood*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism; D013550:Swimming / Q000502:physiology*; D013950:Thymus Gland / Q000033:anatomy & histology
D015306:Biogenic Monoamines; D001786:Blood Glucose; D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D008694:Methamphetamine; D003404:Creatinine; D003401:Creatine; D003345:Corticosterone