Dopamine therapy

Dopamine therapy is the regulation of levels of the neurotransmitter dopamine through the use of either agonists, or antagonists; and has been used in the treatment of disorders characterized by a dopamine imbalance. Dopamine replacement therapy (DRT) is an effective treatment for patients with decreased levels of dopamine. Often dopamine agonists, compounds that activate dopamine receptors in the absence of that receptor's physiological ligand, the neurotransmitter dopamine, are used in this therapy. DRT has been shown to reduce symptoms and increase lifespan for patients with Parkinson's disease. Dopamine regulation plays a critical role in human mental and physical health. The neurons that contain the neurotransmitter are clustered in the midbrain region in an area called the substantia nigra. In Parkinson's patients, the death of dopamine-transmitting neurons in this area leads to abnormal nerve-firing patterns that cause motor problems. Research in patients with schizophrenia indicates abnormalities in dopamine receptor structure and function.

Dopamine therapy
Specialtyneurology

Dopamine replacement therapy in Parkinson's disease

DRT has been used to improve motor skills, impulsivity, and decision making in Parkinson's patients.[1] In Parkinson's disease patients, dopamine deficiencies can be seen in two key areas of the brain: the dorsal frontostriatal circuit, the area responsible for motor skills and task-switching, and the ventral frontostriatal circuit, the area responsible for impulsivity.[1] Impairment in these areas can be treated with dopamine agonists, a group of medications that mimics the ligand dopamine and bonds to dopamine receptors. Other medications that convert into dopamine, as opposed to functioning as dopamine analogs, alleviate the effects of the degeneration of dopamine-producing neurons. One dopamine precursor, Levodopa, was the first drug approved specifically for Parkinson's disease.[2] DRT increases dopamine in the brain to optimal levels in order to return motor skills, impulsivity, and decision making to normal function.[3] Although DRT can improve motor skills and decision making in patients with mild to severe Parkinson's disease, an overdose of dopamine is associated with impaired impulsivity (see next section).

The overdose hypothesis

Dopamine deficiency is more severe in the dorsal frontostriatal circuit than in the ventral frontostriatal circuit.[1] However, DRT does not target these areas differently, and delivers the same amount of dopamine to both areas of the brain. DRT medication can increase dopamine in the dorsal frontostriatal circuit to an optimal level, leading to an improvement in task-switching activities and working memory.[1] Simultaneously, the ventral frontostriatal circuit will experience an overdose of dopamine that will lead to increased impulsive behavior.[1] Problems controlling impulsivity due to DRT drugs have been shown to induce impulsive forms of behavior,[3] such as compulsive gambling.[4] Although DRT drugs can worsen impulse control, a lack of DRT drugs does not necessarily result in better impulse control.[1] Levels of improvement depend on the severity of psychiatric disorder.

Early studies of dopamine therapy in schizophrenia

In patients with schizophrenia, evidence indicates abnormal dopamine receptor D2 structure, as well as a reduced link between dopamine receptor D1 and receptor D2.[5] Studies have shown that targeting the D1 receptors in the prefrontal cortex can improve the cognitive functioning of schizophrenic patients. However, adverse effects of dopamine therapy may occur, including difficulty with impulse control.[6] More research is needed to fully understand the effects of dopamine therapy in patients with schizophrenia.

References
  1. Torta, Diana Maria Elena; Castelli, Lorys; Zibetti, Maurizio; Lopiano, Leonardo; Geminiani, Giuliano (November 2009). "On the role of dopamine replacement therapy in decision-making, working memory, and reward in Parkinson's disease: Does the therapy-dose matter?". Brain and Cognition. 71 (2): 84–91. doi:10.1016/j.bandc.2009.04.003. PMID 19442427. S2CID 30126068.
  2. Vijverman, Anne-Catherine; Fox, Susan H (16 October 2014). "New treatments for the motor symptoms of Parkinson's disease". Expert Review of Clinical Pharmacology. 7 (6): 761–777. doi:10.1586/17512433.2014.966812. PMID 25318835. S2CID 26020088.
  3. Ambermoon, P; Carter, A; Hall, WD; Dissanayaka, NN; O'Sullivan, JD (February 2011). "Impulse control disorders in patients with Parkinson's disease receiving dopamine replacement therapy: evidence and implications for the addictions field". Addiction. 106 (2): 283–93. doi:10.1111/j.1360-0443.2010.03218.x. PMID 21134016.
  4. Avanzi, M; Uber, E; Bonfà, F (June 2004). "Pathological gambling in two patients on dopamine replacement therapy for Parkinson's disease". Neurological Sciences. 25 (2): 98–101. doi:10.1007/s10072-004-0238-z. PMID 15221629. S2CID 21255326.
  5. Seeman, P; Niznik, HB (July 1990). "Dopamine receptors and transporters in Parkinson's disease and schizophrenia". FASEB Journal. 4 (10): 2737–44. doi:10.1096/fasebj.4.10.2197154. PMID 2197154. S2CID 16245677.
  6. Goldman-Rakic, PS; Castner, SA; Svensson, TH; Siever, LJ; Williams, GV (June 2004). "Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction". Psychopharmacology. 174 (1): 3–16. doi:10.1007/s00213-004-1793-y. PMID 15118803. S2CID 25015952.
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