Contrasting responses by basal ganglia met-enkephalin systems to low and high doses of methamphetamine in a rat model.
The influence of methamphetamine (METH) on basal ganglia met-enkephalin (Menk) was studied by determining levels of this peptide in striatal, pallidal and nigral regions after administering a single low (0.5 mg/kg) or high (10 mg/kg) dose of this stimulant. The Menk levels in the striatal and pallidal areas were reduced and increased after the low- and high-dose METH treatments, respectively, 12 h after drug administration in all striatal and pallidal regions examined. The low-dose effect appeared to be principally influenced by increased activation of the dopamine D2-like receptor, while the high-dose effect seemed to result from dominance of D1-like receptor activation. However, both effects required coactivation of D1- and D2-like receptors. For the most part, both low- and high-dose METH-induced changes in Menk tissue content were fully recovered by 24 h. The Menk levels were not significantly altered in the substantia nigra 3-24 h after either METH treatment. Results reported herein indicated that striatal and pallidal Menk pathways respond differently after acute treatment with low or high doses of METH.
Alburges
M E
ME
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA. M.E.Alburges@m.cc.utah.edu
Keefe
K A
KA
Hanson
G R
GR
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000378:metabolism*; D005917:Globus Pallidus / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D013997:Time Factors
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D008694:Methamphetamine; D004744:Enkephalin, Methionine