Protective effects of N-acetylserotonin against 6-hydroxydopamine-induced neurotoxicity.
The present work studied in vivo neuroprotective effects of n-acetylserotonin (NAS), the immediate precursor of melatonin, on the dopaminergic system, in rats lesioned with the unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Two weeks after the lesion, the dopamine receptor agonist, apomorphine, produced rotational asymmetry, and the NAS treatment significantly reduced the motor deficit following the apomorphine challenge. The apomorphine-induced rotational behavior was blocked by 84, 86 and 53% after NAS, at doses of 2, 5 and 10 mg/kg, i.p., respectively. The injection of 6-OHDA significantly decreased DA, DOPAC and HVA levels in the rat striatum. In contrast, the NAS (2, 5 and 10 mg/kg, i.p., daily for 7 days) treatment partially reversed the decreases caused by 6-OHDA, and the neurotransmitter levels were brought to approximately 50% of that observed in the contralateral sides. NAS was more efficient at the smaller doses. NAS (5 mg/kg) produced an up-regulation of D1 (37%) and D2 (37%) receptors associated with a decrease in Kd values.
Aguiar
Lissiana Magna
LM
Universidade Federal do Ceará, Fortaleza, Brazil. lissianamagna@hotmail.com
Macedo
Danielle Silveira
DS
de Freitas
Rivelilson Mendes
RM
de Albuquerque Oliveira
Aline
A
Vasconcelos
Slivânia Maria Mendes
SM
de Sousa
Francisca Cléa F
FC
de Barros Viana
Glauce S
GS
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism; D008297:Male; D008845:Microinjections; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000517:prevention & control*; D016627:Oxidopamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012399:Rotation; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013565:Sympatholytics / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D001552:Benzazepines; D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D012701:Serotonin; D016627:Oxidopamine; D001058:Apomorphine; C006389:N-acetylserotonin; D004298:Dopamine