Effects of L-carnitine pretreatment in methamphetamine and 3-nitropropionic acid-induced neurotoxicity.
Adult, male Sprague-Dawley rats were injected with 3-ni-tropropionic acid (3-NPA) at 30 mg/kg or methamphetamine (METH) at 20 mg/kg alone or following pretreatment with L-cartnitine (LC) at 100 mg/kg. Rectal temperature was measured before and 4 h following treatment. Animals were sacrificed at 4 h posttreatment. Monoamine neurotransmitters, dopamine (DA) and serotonin (5-HT), and their metabolites were analyzed in the striatum using high-performance liquid chromatography method coupled with electrochemical detection (HPLC/ED). Transcripts of several genes related to DA metabolism were quantified using real time reverse transciption polymerase chain reaction (RT-PCR). Core temperature decreased significantly after 3-NPA acid and increased in METH-treated rats (P < 0.05). Temperature change at 4 h exhibited a significant LC effect for 3-NPA, preventing hypothermia (P < 0.05) and no effect for METH. Concentration of DA and 5-HT, and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), increased significantly in 3-NPA and decreased in METH-treated rats. An increase in DOPAC/DA turnover and serotonin observed after 3-NPA was abolished in LC-/3-NPA-treated rats. In both 3-NPA- and METH-treated rats, LC prevented an increase in DA receptor D(1) gene expression. It appears that carnitine effect preventing hypothermia after 3-NPA treatments may be related not only to its mitochondriotropic actions but also to inhibitory effect on the DA and 5-HT systems activated after the exposure to 3-NPA. The same effect observed at the transcriptional level, at least for the DA receptor D(1), may account for protection against METH toxicity.
Binienda
Zbigniew K
ZK
Division of Neurotoxicology, HFT-132, FDA/NCTR, Jefferson, AR 72079-9502, USA. zbinienda@nctr.fda.gov
Przybyla
Beata D
BD
Robinson
Bonnie L
BL
Salem
Nadia
N
Virmani
Ashraf
A
Amato
Antonino
A
Ali
Syed F
SF
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002331:Carnitine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000628:therapy*; D009574:Nitro Compounds / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014803:Vitamin B Complex / Q000494:pharmacology*
D000959:Antihypertensive Agents; D015259:Dopamine Agents; D009574:Nitro Compounds; D011422:Propionates; D014803:Vitamin B Complex; D008694:Methamphetamine; C015392:3-nitropropionic acid; D002331:Carnitine