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The nicotine‐mediated decline in l ‐dopa‐induced dyskinesias is associated with a decrease in striatal dopamine release
Author(s) -
Bordia Tanuja,
McIntosh J. Michael,
Quik Maryka
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12179
Subject(s) - medial forebrain bundle , nicotine , dopaminergic , dopamine , benserazide , dopamine transporter , parkinsonism , pharmacology , oxidopamine , medicine , chemistry , parkinson's disease , levodopa , endocrinology , neuroscience , substantia nigra , psychology , disease
l ‐dopa‐induced dyskinesias (LIDs) are a side effect of Parkinson's disease therapy that is thought to arise, at least in part, because of excessive dopaminergic activity. Thus, drugs that regulate dopaminergic tone may provide an approach to manage LIDs. Our previous studies showed that nicotine treatment reduced LIDs in Parkinsonian animal models. This study investigates whether nicotine may exert its beneficial effects by modulating pre‐synaptic dopaminergic function. Rats were unilaterally lesioned by injection of 6‐hydroxydopamine (6‐OHDA) (2 × 3 ug per site) into the medial forebrain bundle to yield moderate Parkinsonism. They were then implanted with minipumps containing vehicle or nicotine (2.0 mg/kg/d) and rendered dyskinetic with l ‐dopa (8 mg/kg plus 15 mg/kg benserazide). Lesioning alone decreased the striatal dopamine transporter, nicotinic receptor ( nAChR ) levels, and nAChR ‐mediated 3 H‐dopamine release, consistent with previous results. Nicotine administration reduced l ‐dopa‐induced abnormal involuntary movements throughout the course of the study (4 months). Nicotine treatment led to declines in the striatal dopamine transporter, α6β2* nAChR s and various components of α6β2* and α4β2* nAChR ‐mediated release. l ‐dopa treatment had no effect. These data suggest that nicotine may improve LIDs in Parkinsonian animal models by dampening striatal dopaminergic activity.