Editing Dopamine (section)

===Parkinson's disease===

Parkinson's disease is an age-related disorder characterized by [[movement disorder]]s such as stiffness of the body, slowing of movement, and trembling of limbs when they are not in use.<ref name=Jankovic>{{cite journal | vauthors = Jankovic J | title = Parkinson's disease: clinical features and diagnosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 79 | issue = 4 | pages = 368–76 | date = April 2008 | pmid = 18344392 | doi = 10.1136/jnnp.2007.131045 | url = http://jnnp.bmj.com/content/79/4/368.full | doi-access = free }}</ref> In advanced stages it progresses to [[dementia]] and eventually death.<ref name=Jankovic/> The main symptoms are caused by the loss of dopamine-secreting cells in the substantia nigra.<ref name=Dickson>{{cite book | vauthors = Dickson DV|chapter=Neuropathology of movement disorders | veditors = Tolosa E, Jankovic JJ| title=Parkinson's disease and movement disorders |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2007 |pages= 271–83 |isbn=978-0-7817-7881-7}}</ref> These dopamine cells are especially vulnerable to damage, and a variety of insults, including [[encephalitis]] (as depicted in the book and movie ''[[Awakenings]]''), repeated sports-related [[concussion]]s, and some forms of chemical poisoning such as [[MPTP]], can lead to substantial cell loss, producing a [[Parkinsonism|parkinsonian syndrome]] that is similar in its main features to Parkinson's disease.<ref name=Tuite>{{cite journal | vauthors = Tuite PJ, Krawczewski K | title = Parkinsonism: a review-of-systems approach to diagnosis | journal = Seminars in Neurology | volume = 27 | issue = 2 | pages = 113–22 | date = April 2007 | pmid = 17390256 | doi = 10.1055/s-2007-971174 | s2cid = 260319916 }}</ref> Most cases of Parkinson's disease, however, are [[idiopathic]], meaning that the cause of cell death cannot be identified.<ref name=Tuite/>

The most widely used treatment for parkinsonism is administration of L-DOPA, the metabolic precursor for dopamine.<ref name="Nice-pharma"/> L-DOPA is converted to dopamine in the brain and various parts of the body by the enzyme DOPA decarboxylase.<ref name=Musacchio/> L-DOPA is used rather than dopamine itself because, unlike dopamine, it is capable of crossing the [[blood–brain barrier]].<ref name="Nice-pharma">{{cite book| chapter=Symptomatic pharmacological therapy in Parkinson's disease| editor=The National Collaborating Centre for Chronic Conditions| title=Parkinson's Disease| chapter-url=http://guidance.nice.org.uk/CG35/Guidance/pdf/English| access-date=24 September 2015| publisher=Royal College of Physicians| location=London| year=2006| isbn=978-1-86016-283-1| pages=59–100| archive-date=24 September 2010| archive-url=https://web.archive.org/web/20100924153546/http://guidance.nice.org.uk/CG35/Guidance/pdf/English| url-status=dead}}</ref> It is often co-administered with an [[enzyme inhibitor]] of peripheral [[decarboxylation]] such as [[carbidopa]] or [[benserazide]], to reduce the amount converted to dopamine in the periphery and thereby increase the amount of L-DOPA that enters the brain.<ref name="Nice-pharma"/> When L-DOPA is administered regularly over a long time period, a variety of unpleasant side effects such as [[dyskinesia]] often begin to appear; even so, it is considered the best available long-term treatment option for most cases of Parkinson's disease.<ref name="Nice-pharma"/>

L-DOPA treatment cannot restore the dopamine cells that have been lost, but it causes the remaining cells to produce more dopamine, thereby compensating for the loss to at least some degree.<ref name="Nice-pharma"/> In advanced stages the treatment begins to fail because the cell loss is so severe that the remaining ones cannot produce enough dopamine regardless of L-DOPA levels.<ref name="Nice-pharma"/> Other drugs that enhance dopamine function, such as [[bromocriptine]] and [[pergolide]], are also sometimes used to treat Parkinsonism, but in most cases L-DOPA appears to give the best trade-off between positive effects and negative side-effects.<ref name="Nice-pharma"/>

Dopaminergic medications that are used to treat Parkinson's disease are sometimes associated with the development of a [[dopamine dysregulation syndrome]], which involves the overuse of dopaminergic medication and medication-induced compulsive engagement in [[natural reward]]s like gambling and sexual activity.<ref name="Natural and drug addictions">{{cite journal | vauthors = Olsen CM | title = Natural rewards, neuroplasticity, and non-drug addictions | journal = Neuropharmacology | volume = 61 | issue = 7 | pages = 1109–22 | date = December 2011 | pmid = 21459101 | pmc = 3139704 | doi = 10.1016/j.neuropharm.2011.03.010 | quote = <!-- Notably, sensitization processes can also translate between drug and non-drug rewards (Fiorino and Phillips, 1999; Avena and Hoebel, 2003b; Robinson and Berridge, 2008). In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008). --> }}</ref><ref name="DDS in PD">{{cite journal | vauthors = Ceravolo R, Frosini D, Rossi C, Bonuccelli U | s2cid = 19277026 | title = Spectrum of addictions in Parkinson's disease: from dopamine dysregulation syndrome to impulse control disorders | journal = Journal of Neurology | volume = 257 | issue = Suppl 2 | pages = S276–83 | date = November 2010 | pmid = 21080189 | doi = 10.1007/s00415-010-5715-0 }}</ref> The latter behaviors are similar to those observed in individuals with a [[behavioral addiction]].<ref name="Natural and drug addictions" />