Microgliosis and down-regulation of adenosine transporter induced by methamphetamine in rats

Chronic administration of methamphetamine to rats induces neurotoxicity cha racterized by a loss of striatal dopaminergic terminals and reactive gliosi s. Subcutaneous administration of methamphetamine in a scheduled procedure of four doses (10 mg/kg) at 2 h interval also induces a significant increas e in the peripheral-type benzodiazepine receptor (PBR) density. This increa se is maximum (76%) at 72 h post-treatment in the striatum and disappears a t 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 i n cerebellum (75.4% of PER increase) and hippocampus (37.2% of PER increase ). In the areas with high density of adenosine transporter, the microgliosi s phenomenon correlates well with a decrease of this nucleoside transporter (about 39%). Although the microgliosis and the decrease in adenosine trans porter 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, meth amphetamine induces HSP72 expression in both cytoplasmic and nuclear fracti ons of the striatum, cerebellum and hippocampus. This expression is also ev ident in the cerebral cortex, where adenosine transporter population did no t show any variation. (C) 1998 Elsevier Science B.V. All rights reserved.