Carnosine prevents methamphetamine-induced gliosis but not dopamine terminal loss in rats.
The neuroprotective effect of carnosine, an endogenous antioxidant, was examined against methamphetamine-induced neurotoxicity in rats. Carnosine pretreatment had no effect on dopamine terminal loss induced by methamphetamine (assessed by [3H]1-(2-[diphenylmethoxy]ethyl)-4-[3-phenylpropyl]piperazine([3H]GBR 12935) binding) but prevented microgliosis (increase in [3H]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide ([3H]PK 11195) binding) in striatum. The 27-kDa heat-shock protein (HSP27) expression was used as indicator of astroglial stress. Methamphetamine treatment induced the expression of HSP27 in striatum and hippocampus, which was inhibited by carnosine, indicating a protective effect. Carnosine had no effect on methamphetamine-induced hyperthermia. Thus, carnosine prevents the microgliosis in striatum (where we did not detect loss of serotonergic terminals by [3H]paroxetine binding) and the expression of HSP27 in all the areas, but fails to prevent methamphetamine-induced loss of dopamine reuptake sites. Therefore, carnosine inhibits only some of the consequences of methamphetamine neurotoxicity, where reactive oxygen species play an important role.
Pubill
David
D
Unitat de Farmacological i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Avgda. Diagonal 643, 08028 Barcelona, Spain.
Verdaguer
Ester
E
Sureda
Francesc X
FX
Camins
Antoni
A
Pallàs
Mercè
M
Camarasa
Jordi
J
Escubedo
Elena
E
D000818:Animals; D002336:Carnosine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced* / Q000517:prevention & control*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D010879:Piperazines / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*
D010879:Piperazines; D011954:Receptors, Dopamine; D008694:Methamphetamine; D002336:Carnosine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine