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Is nicotine protective against Parkinson's disease? An experimental analysis.

Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and its projections. Reports show a lower incidence of PD in smokers compared to nonsmokers. Nicotine reduce motor symptoms of patients already diagnosed with PD. However, the mechanisms underlying the effects of nicotine in the dopamine (DA) depleted striatum remain elusive. This study evaluates the effects of chronic nicotine administration on PD motor symptoms in an attempt to mimic the chronic self-administration of nicotine in smokers. To achieve this, we used the 6-OHDA hemiparkinson rat model evaluating the amphetamine/apomorphine induced circling behavior, in rats whose daily water intake included nicotine. We found that chronic nicotine reduced amphetamine (AMPH) induced circling behavior by 40%, whereas apomorphine (APO) increased this behavior by 230%. High-performance liquid chromatography (HPLC) revealed that AMPH produced a 50% decrease of DA release in the intact hemisphere, while on the striatum of the lesioned side, receptor binding assays showed an increased affinity to D1 receptors and a concurrent decrease in D2 receptors. c-Fos activity showed through double labeling, that cell types involved in nicotine action were low threshold (LTS) and fast spiking (FS) inter-neurons, which increased in the DA-depleted striatum. We also observed an increase in the activity of D1 medium spiny neurons (D1 MSN), a striatal population with a major role in motor control. Our results show that chronic nicotine does not specifically protect against degeneration, but rather modifies DA receptor dynamics, suggesting that it could be used as a therapeutic element in PD pathology.
AuthorsJosé-Rubén García-Montes, Alejandra Boronat-García, Ana-María López-Colomé, José Bargas, Magdalena Guerra-Crespo, René Drucker-Colín
JournalCNS & neurological disorders drug targets (CNS Neurol Disord Drug Targets) Vol. 11 Issue 7 Pg. 897-906 (Nov 1 2012) ISSN: 1996-3181 [Electronic] United Arab Emirates
PMID23131151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiparkinson Agents
  • Dopamine Agents
  • Dopamine D2 Receptor Antagonists
  • Dopamine Uptake Inhibitors
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Nicotine
  • Oxidopamine
  • Amphetamine
  • Apomorphine
  • Dopamine
Topics
  • Amphetamine (adverse effects)
  • Animals
  • Antiparkinson Agents (therapeutic use)
  • Apomorphine (therapeutic use)
  • Behavior, Animal (drug effects)
  • Corpus Striatum (drug effects, metabolism, pathology)
  • Disease Models, Animal
  • Dopamine (metabolism, secretion)
  • Dopamine Agents (therapeutic use)
  • Dopamine D2 Receptor Antagonists
  • Dopamine Uptake Inhibitors (adverse effects)
  • Interneurons (drug effects, metabolism, secretion)
  • Male
  • Nerve Tissue Proteins (agonists, antagonists & inhibitors, metabolism)
  • Neuroprotective Agents (therapeutic use)
  • Nicotine (therapeutic use)
  • Oxidopamine
  • Parkinson Disease (metabolism, pathology, prevention & control)
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 (agonists, antagonists & inhibitors, metabolism)
  • Receptors, Dopamine D2 (agonists, metabolism)
  • Substantia Nigra (drug effects, metabolism, pathology)

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