CSC, an adenosine A(2A) receptor antagonist and MAO B inhibitor, reverses behavior, monoamine neurotransmission, and amino acid alterations in the 6-OHDA-lesioned rats.
The present work showed the effects of 8-(-3-chlorostyryl)-caffeine (CSC), an A(2A) receptors antagonist and MAO B inhibitor, on behavior and biochemical alterations in 6-OHDA-lesioned rats. Male Wistar rats (280 g) were injected with CSC (1 and 5 mg/kg, i.p.) alone or combined with l-DOPA (50 mg/kg+benserazide 12.5 mg/kg), starting 6 days after the striatal 6-OHDA lesions, and once daily for the next 7 days. Fourteen days after the 6-OHDA lesion (and 24 h after CSC or vehicle), the number of net body rotations/h (after the apomorphine challenge) was recorded and, at the next day, animals were sacrificed. The ipsilateral striatum was used for HPLC measurements of monoamines and amino acids or for determination of nitrite contents and lipid peroxidation. Results showed that the increase in body rotation, induced by the 6-OHDA lesion, after the apomorphine challenge, was significantly and dose-dependently reversed by CSC. Furthermore, the decreased striatal levels of DA and metabolites, in the 6-OHDA-lesioned rats, were reversed after CSC treatment, and these effects were potentiated after the combination with l-DOPA. Similar results were observed with NE, 5-HT and 5-HIAA. While glutamate and GABA were increased in the 6-OHDA-lesioned group, CSC alone or mainly combined with l-DOPA reversed these alterations. In addition, the CSC treatment of 6-OHDA-lesioned rats reversed the increased nitrite formation and lipid peroxidation induced by 6-OHDA. In conclusion, CSC by means of its dual action as A(2A) antagonist and MAO-B inhibitor reversed behavior and biochemical alterations, observed in the 6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of PD.
Aguiar
Lissiana M V
LM
Laboratory of Neuropharmacology, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo 1127, CEP 60431-970, Fortaleza, Brazil.
Macêdo
Danielle S
DS
Vasconcelos
Silvania M M
SM
Oliveira
Aline A
AA
de Sousa
F Cléa F
FC
Viana
Glauce S B
GS
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D012399:Rotation; D012701:Serotonin / Q000378:metabolism
D058908:Adenosine A2 Receptor Agonists; D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D009573:Nitrites; D043683:Receptors, Adenosine A2; C081320:8-(3-chlorostyryl)caffeine; D012701:Serotonin; D002110:Caffeine; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; D008995:Monoamine Oxidase; D009638:Norepinephrine