Protective effects of N-acetylserotonin against 6-hydroxydopamine-induced neurotoxicity

• Published in: Life sciences (1973) 2005-03, Vol.76 (19), p.2193-2202
• Main Authors: Aguiar, Lissiana Magna, Macedo, Danielle Silveira, de Freitas, Rivelilson Mendes, de Albuquerque Oliveira, Aline, Vasconcelos, Slivânia Maria Mendes, de Sousa, Francisca Cléa F., de Barros Viana, Glauce S.
• Format: Article
• Language: English
• Subjects: 6-OHDA; Animals; Apomorphine - pharmacology; Benzazepines - metabolism; Binding, Competitive - drug effects; Biogenic Monoamines - metabolism; Cell Count; Dopamine - metabolism; Dopamine Agonists - pharmacology; Dopamine Antagonists - metabolism; Dopamine receptors; Male; Microinjections; Monoamine levels; N-acetylserotonin; Neostriatum - drug effects; Neostriatum - metabolism; Neostriatum - pathology; Neurons - drug effects; Neurons - pathology; Neuroprotection; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - prevention & control; Oxidopamine - administration & dosage; Oxidopamine - antagonists & inhibitors; Oxidopamine - toxicity; Parkinson's disease; Rats; Rats, Wistar; Receptors, Dopamine D1 - drug effects; Receptors, Dopamine D2 - drug effects; Rotation; Rotational behavior; Serotonin - analogs & derivatives; Serotonin - metabolism; Serotonin - pharmacology; Stereotyped Behavior - drug effects; Sympatholytics - administration & dosage; Sympatholytics - antagonists & inhibitors; Sympatholytics - toxicity
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2004.09.035

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.