# Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Nicotine

   The long term adverse health consequences of inhaling nicotine have been well documented, but it can be administered in less harmful forms such as skin patches.

## Background

Nicotine is an alkaloid found in the nightshade family of plants, where it functions as a deterrent to herbivores. Its formula is 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine. It is the active component of tobacco which, when inhaled by humans, is both a stimulant and a relaxant. It instigates a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla. Users report feelings of relaxation, sharpness, calmness and alertness.

## Research

1990
Carr and Rowell exposed mice to tobacco smoke for 4 weeks, then induced Parkinson symptoms using MPTP and evaluated the results.
   Smoke exposure was found to reduce the decrease in striatal dopamine and metabolite levels caused by MPTP. Although smoke exposure inhibited cerebral MAO-B activity, tissues from smoke-treated mice were able to metabolize MPTP in a normal fashion. This suggests that inhibition of cerebral MAO may not be a major mechanism for the apparent protective effect of cigarette smoke.
1998
Ferger et al carried out a series of experiments with nicotine added in vitro to dopaminergic neuron cells and nicotine injections in mice with MPTP-induced Parkinsonism. Their findings:-
   These results demonstrate that in vitro nicotine has radical scavenging properties which might suggest neuroprotective effects. In vivo experiments with nicotine, however, showed that a low dosage of nicotine did not alleviate the MPTP-induced dopamine depletion, but a large dosage even enhanced it.
2001
Costa et al induced Parkinsonism in rats by the administration of 6-OHDA and then assessed the effects of the injection of nicotine.
   Subcutaneous nicotine (1 mg/kg) administered 4 h before and 20, 44 and 68 h after 6 microg 6-OHDA, prevented significantly the striatal dopamine loss. Administered only 18 or 4 h before or only 20, 44 and 68 h after, nicotine failed to counteract the loss of dopamine or the increase in dopamine turnover observed in the CS. Nicotine also failed to prevent significantly the decrease of striatal dopamine levels produced by the 10-microg 6-OHDA intranigral dose. Chlorisondamine, a long-lasting nicotinic acetylcholine receptor antagonist, reverted significantly the nicotinic protective effects on dopamine concentrations. These results are showing that putative neuroprotective effects of nicotine in vivo depend on an acute intermittent administration schedule and on the extent of the brain lesion.
2002
Meshul et al evaluated the effects of nicotine on Parkinsonian rats.
   The overall goal of this study was to determine the effects of subchronic nicotine (0.4 mg/kg) treatment for 7 or 14 days on striatal glutamate function in both naïve and in 6-hydroxydopamine (6-OHDA)-treated rats in which the nigrostriatal dopamine pathway was lesioned.
   The data suggests that in this 6-OHDA lesion model of Parkinson's disease, treatment with nicotine may be useful in counteracting the increased behavioral effect (i.e., contralateral rotations) observed after treatment with a dopamine agonist, such as apomorphine.
2003
Tan et al. See report under Caffeine.
2004
Quik reviewed the microbiology of nicotine.
   Putative factors and signalling pathways involved in the actions of nicotine are discussed. An understanding of the molecular basis for the reduced occurrence of PD in tobacco users is crucial for the development of intervention strategies to reduce or halt disease progression
2006
Quik et al administered nicotine to monkeys in drinking water for 6 months and then induced Parkinsonism through injections of MPTP. Tests indicated that the nicotine treated monkeys fared better than a similar batch that were not given nicotine.
   MPTP-induced cell loss in the substantia nigra was unaffected by nicotine treatment, indicating that nicotine acts at the striatal level to restore/maintain dopaminergic function. These data further support the possibility that nicotine contributes to the lower incidence of Parkinson's disease in smokers.
2007
Ritz et al evaluated the risk of PD in relation to smoking.
   Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.
2009
Simon et al published the results of an epidemiological study which showed that:-
   Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use. Use of postmenopausal hormones, however, may modify the associations of smoking and caffeine intake with PD risk.
2010
Trin et al. See report under Caffeine,--

## Further Reading

Today
   Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease Nicotine.
   This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.
Pubmed (abstracts)
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## Related pages

Therapy > Neuroprotection
Sub Pages:
    Neuroprotective agents
    Substances with possible neuroprotective properties:
    Caffeine,--Celastrol,--Co-Enzyme Q10,--Creatine,--DHA,--Exendin-4 (EX-4),--GDNF,--Glutathione (GSH),--GM1,--Isradipine,--Melatonin,--Minocycline,--Nicotine,--NSAIDs,--Phenylbutyrate,--Phytic Acid,--Probucol,--Quinoxaline,--Rasagiline,--Riboflavin,--Statins,--Tolcapone,--Urate & Uric Acid,--Vitamin D,--Vitamin E,--