In vivo studies on the protective role of minocycline against excitotoxicity caused by malonate or N-methyl-d-aspartate.
Minocycline has been shown to exert neuroprotection against a wide variety of toxic insults both in vitro and in vivo. However, contradictory results have recently been reported. We now report that minocycline affords no protection against the neurotoxicity caused by malonate or N-methyl-d-aspartate (NMDA). Rats were treated with minocycline (45 mg/kg i.p. x 7) every 12 h. Thirty minutes after the second dose of minocycline, an intrastriatal stereotaxic injection of malonate (1.5 mumol) or NMDA (0.1 mumol) was administered. Seven days later, the rats were killed, and lesion volumes were quantified using two different methods [triphenyltetrazolium chloride (TTC) staining or cytochrome oxidase histochemistry]. Our results show that minocycline does not prevent the lesions caused by either malonate or by NMDA. On the contrary, the putative NMDA receptor antagonist, MK-801, blocked the toxicity caused by both toxins indicating that, although by different mechanisms, excitotoxicity is mediating neuronal death. We conclude that minocycline, at least under our experimental conditions, is not neuroprotective against excitotoxicity caused by either malonate or NMDA.
Goñi-Allo
Beatriz
B
Departamento de Farmacología, Facultad de Medicina, Universidad de Navarra, C/Irunlarrea, 1, 31008 Pamplona, Spain.
Ramos
María
M
Jordán
Joaquín
J
Aguirre
Norberto
N
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D008297:Male; D008314:Malonates / Q000633:toxicity*; D008911:Minocycline / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000633:toxicity*; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000517:prevention & control; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D008314:Malonates; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C030290:malonic acid; D008911:Minocycline