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Endogenous melatonin protects L ‐DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long‐term L ‐DOPA therapy in Parkinson's disease
Author(s) -
Rocchitta Gaia,
Migheli Rossana,
Esposito Giovanni,
Marchetti Bianca,
Desole Maria S.,
Miele Egidio,
Serra Pier Andrea
Publication year - 2006
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2005.00299.x
Subject(s) - microdialysis , melatonin , chemistry , extracellular , benserazide , autoxidation , endogeny , endocrinology , dopamine , catecholamine , medicine , dihydroxyphenylalanine , ascorbic acid , in vivo , pharmacology , levodopa , biochemistry , biology , parkinson's disease , food science , disease , microbiology and biotechnology
We previously showed, using microdialysis, that autoxidation of exogenous L‐dihydroxyphenylalanine ( l ‐DOPA) occurs in vivo in the extracellular compartment of the freely moving rat, with a consequent formation of l ‐DOPA semiquinone ( l ‐DOPA‐SQ). In the present study, intrastriatal infusion of l ‐DOPA (1.0 μ m for 200 min) increased dialysate l ‐DOPA concentrations (maximum increases up to 116‐fold baseline values); moreover, l ‐DOPA‐SQ was detected in dialysates. Individual dialysate concentrations of l ‐DOPA were negatively correlated with those of l ‐DOPA‐SQ. Co‐infusion of N ‐acetylcysteine (100 μ m ) or melatonin (50 μ m ) increased l ‐DOPA (up to 151‐ and 246‐fold, respectively) and decreased l ‐DOPA‐SQ (by about 53% and 87%, respectively) dialysate concentrations. Systemic l ‐DOPA [25 mg/kg intraperitoneally (i.p.) twice in a 12‐h interval] significantly increased striatal baseline dialysate concentrations of l ‐DOPA and decreased dopamine (DA) and ascorbic acid (AsAc) concentrations, when compared with controls. Following systemic l ‐DOPA, l ‐DOPA‐SQ was detected in dialysates. Endogenous melatonin was depleted in rats maintained on a 24‐h light cycle for 1 wk. In melatonin‐depleted rats, systemic l ‐DOPA induced a smaller increase in dialysate l ‐DOPA, a greater increase in l ‐DOPA‐SQ formation, and a greater reduction in DA and AsAc dialysate concentrations. Co‐administration of melatonin (5.0 mg/kg, i.p., twice in a 12‐h interval) with l ‐DOPA, in control as well as in light‐exposed rats, significantly increased dialysate l ‐DOPA concentrations, greatly inhibited l ‐DOPA‐SQ formation, and restored up to the control values dialysate DA and AsAc concentrations. These findings demonstrate that endogenous melatonin protects exogenous l ‐DOPA from autoxidation in the extracellular compartment of the striatum of freely moving rats; moreover, systemic co‐administration of melatonin with l ‐DOPA markedly increases striatal l ‐DOPA bioavailability in control as well as in melatonin‐depleted rats. These results may be of relevance to the long‐term l ‐DOPA therapy of Parkinson's disease.