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.
Keywords: Basal ganglia, chronic nicotine, dopamine receptor, inter-neurons, Parkinson´s disease, striatum, neurodegenerative disorder, dopaminergic neurons, amphetamine, HPLC
CNS & Neurological Disorders - Drug Targets
Title:Is Nicotine Protective Against Parkinson´s Disease? An Experimental Analysis
Volume: 11 Issue: 7
Author(s): Jose-Ruben Garcia-Montes, Alejandra Boronat-Garcia, Ana-Maria Lopez-Colome, Jose Bargas, Magdalena Guerra-Crespo and Rene Drucker-Colin
Affiliation:
Keywords: Basal ganglia, chronic nicotine, dopamine receptor, inter-neurons, Parkinson´s disease, striatum, neurodegenerative disorder, dopaminergic neurons, amphetamine, HPLC
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.
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Garcia-Montes Jose-Ruben, Boronat-Garcia Alejandra, Lopez-Colome Ana-Maria, Bargas Jose, Guerra-Crespo Magdalena and Drucker-Colin Rene, Is Nicotine Protective Against Parkinson´s Disease? An Experimental Analysis, CNS & Neurological Disorders - Drug Targets 2012; 11 (7) . https://dx.doi.org/10.2174/1871527311201070897
DOI https://dx.doi.org/10.2174/1871527311201070897 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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