Age-dependent differential responses of monoaminergic systems to high doses of methamphetamine.
Abuse of methamphetamine (METH) by adolescents is a major public health issue in the U.S.A. Because of the neurotoxic potential of METH, we examined the response of CNS monoaminergic systems in young (adolescent) animals [postnatal day (PND) 40] to high-dose treatments (10 mg/kg, four injections, 2-h intervals) of this drug and contrasted these effects to those seen in older (young adult) rats (PND 90). Consistent with previous reports, we observed that PND 40 animals did not manifest the long-term (7-day) deficits in extrapyramidal dopamine (DA) parameters observed in PND 90 rats. In contrast, METH-induced rapid (1-h) reduction in the activity of striatal DA transporters occurred in both age groups. In addition, both persistent (7-day) and rapid (1-h) deficits in serotonergic systems (measured as reductions in tryptophan hydroxylase activity) were observed in PND 40 and 90 rats. Age-related differences in METH-induced hyperthermia did not appear to be a principal cause for our observations; however, age-dependent pharmacokinetics of this drug might have contributed to the differential METH monoaminergic responses by PND 40 and 90 animals.
Kokoshka
J M
JM
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.
Fleckenstein
A E
AE
Wilkins
D G
DG
Hanson
G R
GR
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005334:Fever / Q000139:chemically induced; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008694:Methamphetamine / Q000008:administration & dosage* / Q000097:blood; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D004298:Dopamine