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The central aromatic amino acid DOPA decarboxylase inhibitor, NSD‐1015, does not inhibit l ‐DOPA‐induced circling in unilateral 6‐OHDA‐lesioned‐rats
Author(s) -
Treseder Sarah A.,
Rose Sarah,
Jenner Peter
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2000.01370.x
Subject(s) - homovanillic acid , carbidopa , aromatic l amino acid decarboxylase , dopamine , benserazide , chemistry , decarboxylase inhibitor , microdialysis , striatum , pharmacology , endocrinology , medicine , 3,4 dihydroxyphenylacetic acid , levodopa , parkinson's disease , serotonin , biochemistry , receptor , disease
The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3‐hydroxybenzyl hydrazine (NSD‐1015), is widely used to study the neurotransmitter‐like actions of l ‐DOPA. However, the effects of NSD‐1015 on l ‐ DOPA ‐induced motor activity are unclear as both increases and decreases have been reported. We now investigate the effects of NSD‐1015 on l ‐DOPA‐induced contralateral circling behaviour in 6‐OHDA‐lesioned rats and on striatal levels of l ‐DOPA, 3‐O‐methyl‐DOPA (3‐OMD), dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) using microdialysis techniques. NSD‐1015 (50–200 mg/kg i.p.) inhibited AADC activity both in the liver and striatum of normal rats. Administration of NSD‐1015 (50–200 mg/kg i.p.), delayed the onset of circling produced by administration of l ‐DOPA (25 mg/kg i.p.) and carbidopa (12.5 mg/kg i.p.), suggesting blockade of central AADC activity. However, the duration of the l ‐DOPA‐induced circling was prolonged and overall no inhibition of circling behaviour occurred. l ‐DOPA (25 mg/kg i.p.) plus carbidopa (12.5 mg/kg i.p.) increased extracellular levels of l ‐DOPA, 3‐OMD, dopamine, DOPAC and HVA in the 6‐OHDA‐lesioned striatum. Pretreatment of rats with the central AADC inhibitor, NSD‐1015 (100 mg/kg i.p.), potentiated the increase in dialysate levels of l ‐DOPA and 3‐OMD. However, it did not reduce striatal dopamine levels in the 6‐OHDA‐lesioned hemisphere, which were elevated following l ‐DOPA administration. The increases in DOPAC and HVA levels were abolished by NSD‐1015 pretreatment. These results suggest that, while NSD‐1015 blocks central AADC activity, it also acts as a monoamine oxidase inhibitor so maintaining striatal dopamine concentration by reducing dopamine metabolism. NSD‐1015, therefore, may not be an appropriate tool for the study of brain AADC activity and for assessing the neuromodulatory role of l ‐DOPA.