CroniconO P E N A C C E S S EC NEUROLOGY

Literature Review Article

Parkinson’s Disease and Drug Abuse

Kaushalendra Tripathi1* and Richa Tripathi2

1Department of Neurology/Internal Medicine, Smt NHL Medical Municipal College, India2Department of Neurology , Emory University Atlanta Georgia, USA

*Corresponding Author: Kaushalendra Mani Tripathi, Department of Neurology/Internal Medicine, Smt NHL Medical Municipal College, India.

Citation: Kaushalendra Tripathi and Richa Tripathi. “Parkinson’s Disease and Drug Abuse”. EC Neurology 7.3 (2017): 117-127.

Received: July 17, 2017; Published: July 26, 2017

AbstractBackground: Parkinson’s disease is described as hypokinetic symptoms with cardinal features such as tremors, bradykinesia, gait difficulties as well as cognitive problems. Much research has been done with regards to drugs of abuse such as opiates, amphet-amines, cocaine as well as therapeutic drugs causing this disease.

Keywords: Parkinson’s; Drugs of Abuse

Methods: I present different reports collected of different drug interactions along with their studies, in an attempt to assimilate all the results and come to a conclusion.

Results: Use of drugs such as heroin, Methcathinone, inhalants, amphetamines, cocaine as well as therapeutic drugs such as pro-kinetic and SSRIs may predispose persons to Parkinson’s disease though NSAIDs have no such association.

Objectives: To provide a brief literature review in context to different reports with Parkinson’s and drug abuse and understand the implications of drugs on basal ganglia circuitry.

Introduction

Parkinson’s Disease (PD) is a multisystem neurodegenerative disorder which is characterized by loss of dopaminergic neurons in the midbrain which leads to characteristic symptoms of slowing of movement, muscular rigidity and resting tremor [1]. Parkinsonism is de-fined by the same clinical features as seen in Parkinson’s Disease but entails as separate form of pathophysiology as seen in diffuse Lewy body disease, multiple system atrophy, progressive supranuclear palsy, encephalitis, brain injury, Wilsons disease, brain damage caused by anaesthesia drugs (such as during surgery), carbon monoxide poisoning, mercury poisoning and other chemical poisonings, overdoses of narcotics, MPTP (a contaminant in some street drugs) [2].

Here we shall discuss the correlation between drug abuse and Parkinson’s disease by first delving into the pathophysiology of the disease, correlating the mechanism of drug action with the addiction circuit and reviewing the overall interaction of the drugs that lead to the development of Parkinson’s disease.

Conclusions: Effect of such drugs in causing Parkinson’s should be discussed with patients on a clinical basis especially in the con-text of drug abuse.

Common symptoms include: Decrease in facial expressions, difficulty starting and controlling movement, Soft voice, Stiffness of the trunk, arms, or legs, tremor, mental confusion and memory loss leading to dementia. Several drugs have been implicated in secondary parkinsonism. These usually include antipsychotics, antiemetics, antidopaminergics.

Pathophysiology of Parkinsonism and addiction pathway

The Basal Ganglia consists of an organized group of nuclei which include the Caudate, Putamen, Globus Pallidus, Subthalamic Nucleus (STN), and Substantia Nigra are located deep to the cortex that surround the Thalamus and are superior to the brainstem. They process the information received to coordinate movement. It consists of 4 main pathway or loops, these are Motor, Oculomotor, Prefrontal, and Limbic loop, the loops relevant to motor functions are motor and oculomotor loop.

The primary motor, premotor (lateral premotor and supplementary motor) and Somatosensory cortices to the Striatum, in particular the Putamen. sends input to the motor loop, this input then returns back to the Motor region through the Ventral Anterior (VA) and Ventral Lateral (VL) nuclei of the Thalamus after it has been thoroughly processed.

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Citation: Kaushalendra Tripathi and Richa Tripathi. “Parkinson’s Disease and Drug Abuse”. EC Neurology 7.3 (2017): 117-127.

The Posterior Parietal cortex and Prefrontal cortex transfer input signals to the oculomotor loop which it sends to the body of the Caudate in the Striatum. After processed the signal is sent back to the Frontal Eye Fields and the Supplementary Eye Fields via the Me-diodorsal and VA of the Thalamus. The direct pathway beings with the cortex first stimulating the stratum. The Striatum then inhibits the internal segment of the Globus Pallidus and the Substantia Nigra pars reticulata with the neurotransmitters GABA or Substance P (Sub P). leading to these structures being unable to inhibit the Thalamus rendering it free to fire and send excitatory input signals up to the Cortex, which facilitates movement.

Cholinergic (ACh) Striatal Interneurons

The cholinergic interneurons located within the Striatum synapse with the indirect and direct pathway with an effect antagonistic to that of dopamine. Release of ACh leads to the inhibition of the direct pathway and excitation of the indirect pathway Parkinsonism is the result of the lesion of the substantia nigra which leads to its inability to excite the direct pathway nor inhibit the indirect pathway, this leads to the neurological manifestations associated with decreased movement. Dopamine when there is an increase in dopaminergic activity when an action has occurred, the circuit in the basal ganglia is modified to elicit the response even quicker if the same situation arises again This is a form of reward signal in which dopamine plays a significant role [1].

Several authors have described possible specific cause triggering death of dopaminergic neurons in the substantia nigra, drug of abuse-induced neurotoxicity, is being considered as a potential mechanism to develop PD [7]. Effects of methamphetamine in Parkinson’s Disease on animal models have demonstrated loss of dopaminergic neurons and decrease in markers of dopamine such as Tyrosine Hy-droxylase and Dopamine Transporter (DAT) [8].

Mesolimbic pathway, which involves the ventral tegmental area ending in the nucleus accumbens in the central striatum and extending into other areas such as amygdala, Bed Nucleus of Stria terminals, hypothalamus plays a key role in reward [11]. Various drugs are in-volved with this pathway by directly or indirectly interacting with different receptors of this pathway. Drugs such as Cocaine and amphet-amine increase the synaptic action of Dopamine by blocking its presynaptic uptake and increasing its release from vesicles respectively [3]. Other drugs like phencyclidine (which blocks reuptake of dopamine and increase the cell firing of dopamine) [3,5], nicotine products (agonists at nicotinic cholinergic receptors), alcohol, heroin, morphine (activating dopamine via VTA GABAergic disinhibition) [3,4] and caffeine (an antagonist at striatal adenosine A2 receptors) [3,6] also acts on the mesolimbic pathway more so at the Nucleus accumbens and is responsible for the psychostimulant as well as rewarding effect.

Baumgarten and Zimmerman (1992) described several ways of cell death from ischemic damage, elevated intracellular calcium levels from glutamate excitation leading to cell death and direct neurotoxicity from the toxin which are formed by auto-oxidation of endogenous neurotransmitters (DA and 5-HT) [9].

The aim of the article is to provide an overview of drug interactions with the limbic circuitry and conclude its involvement in the development of Parkinson’s or not. The given table below discusses different reports that conclude their observations on how different drugs maybe be involved in the development of Parkinson’s disease, the given table contains three columns of which the first states the

The indirect pathway begins with the cortex stimulating the striatum (just like the direct pathway). Then Striatal neurons send inhibi-tory input to the external segment of the Globus Pallidus using the neurotransmitters GABA or Enkephalin (enk). The striatum inhibits the Globus pallidus from sending inhibitory signals to the The Subthalamic Nucleus, the nucleus now being uninhibited sends only excitatory input within the Basal Ganglia pathways to the Globus Pallidus internal segment and the Substantia Nigra pars reticulate followed by these structures then inhibiting the VA and VL of the thalamus making it unable to send excitatory input to the Cortex and thus indirectly inhibiting the Motor Cortices, which inhibits movement.

The normal functioning Substantia Nigra pars compacta facilitates movement and inhibits unintended movement. It does this by ex-citing the direct pathway and inhibiting the indirect pathway through release of the neurotransmitter Dopamine. Striatal neurons have D1 and D2 receptors which are acted upon by dopamine to excite and inhibit them respectively The Substantia Nigra pars compacta also sends excitatory input directly to the Cortex again using Dopamine.

Addiction and reward centres in the brain

Discussion

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Citation: Kaushalendra Tripathi and Richa Tripathi. “Parkinson’s Disease and Drug Abuse”. EC Neurology 7.3 (2017): 117-127.

report, the second states the drugs and/or their respective studies involved and the third concludes the report with results, observations or explanation of their mechanism of action in the development of Parkinson’s. Here many drugs have been discussed, some with a higher propensity to Parkinson’s disease as compared to others.

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Citation: Kaushalendra Tripathi and Richa Tripathi. “Parkinson’s Disease and Drug Abuse”. EC Neurology 7.3 (2017): 117-127.

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Citation: Kaushalendra Tripathi and Richa Tripathi. “Parkinson’s Disease and Drug Abuse”. EC Neurology 7.3 (2017): 117-127.

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Citation: Kaushalendra Tripathi and Richa Tripathi. “Parkinson’s Disease and Drug Abuse”. EC Neurology 7.3 (2017): 117-127.

Results

Use of drugs such as heroin, Methcathinone, inhalants, amphetamines, cocaine as well as therapeutic drugs such as pro-kinetic and SSRIs may predispose persons to Parkinson’s disease though NSAIDs have no such association.

Conclusion

From the given observations in the table, cohort studies coupled with molecular studies have established a relationship between chronic amphetamine abuse and Parkinson’s disease, though cocaine use has not displayed a propensity to Parkinson’s disease, its chron-ic use may lead to subtle features of Parkinson’s disease, it may have therapeutic effects and ameliorate parkinsonian “off” periods, Methcathinone displays similar results to methamphetamine. Opioid abuse requires further studies to establish a relationship to its role in development of Parkinson’s disease, the contaminants in heroin abuse containing MPTP have developed acute, levodopa-responsive parkinsonism. Inhalant exposure to solvents such as toluene, xylene and paint thinners may cause tremor, and, in chronic users, parkin-sonism. DIP (drug induced parkinsonism) has been observed in GI prokinetic drugs and SSRIs which also interact with the D1 and D2 receptor, especially as antagonists to D2, hence causing Parkinson’s disease. There is no association with the use of NSAIDS and Parkin-son’s disease.

It is important to establish a direct correlation with replication of results on a cellular level basis or animal model to show the changes specifically expected from the patients that present with Parkinson’s disease at the clinics, further radiological studies such as fMRI, DTI scans and other various methods, maybe help with specific areas in addiction and clinically with Parkinson’s.

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