Microgliosis and down-regulation of adenosine transporter induced by methamphetamine in rats.
Chronic administration of methamphetamine to rats induces neurotoxicity characterized by a loss of striatal dopaminergic terminals and reactive gliosis. Subcutaneous administration of methamphetamine in a scheduled procedure of four doses (10 mg/kg) at 2 h interval also induces a significant increase in the peripheral-type benzodiazepine receptor (PBR) density. This increase is maximum (76%) at 72 h post-treatment in the striatum and disappears at 7 days, suggesting that microglia may have a predominant role in necrosis-phagocytosis of neuronal debris rather than acting in a restorative manner. Microgliosis is not restricted to the striatum since it is also evident in cerebellum (75.4% of PBR increase) and hippocampus (37.2% of PBR increase). In the areas with high density of adenosine transporter, the microgliosis phenomenon correlates well with a decrease of this nucleoside transporter (about 39%). Although the microgliosis and the decrease in adenosine transporter could be parallel and not related events, we can speculate that when microglia are activated, a down-regulation of adenosine transporter occurs, playing a role in tissue homeostasis. With the same dosing schedule, methamphetamine induces HSP72 expression in both cytoplasmic and nuclear fractions of the striatum, cerebellum and hippocampus. This expression is also evident in the cerebral cortex, where adenosine transporter population did not show any variation.
Escubedo
E
E
Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Nucli Universitari de Pedralbes, 08028, Barcelona, Spain. escubedo@far.ub.es
Guitart
L
L
Sureda
F X
FX
Jiménez
A
A
Pubill
D
D
Pallàs
M
M
Camins
A
A
Camarasa
J
J
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D005911:Gliosis / Q000139:chemically induced* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D008694:Methamphetamine; D000241:Adenosine