Dopamine dysregulation syndrome

Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken dopamine agonist medications for an extended period of time. It is characterized by self-control problems such as addiction to medication, gambling, or sexual behavior.

Parkinson's disease is a common neurological disorder characterized by a degeneration of dopamine neurons in the substantia nigra and a loss of dopamine in the putamen. It is described as a motor disease, but it also produces cognitive and behavioral symptoms. The most common treatment is dopamine replacement therapy, which consists in the administration of levodopa (L-Dopa) or dopamine agonists (such as pramipexole or ropinirole) to patients. Dopamine replacement therapy is well known to improve motor symptoms but its effects in cognitive and behavioral symptoms are more complex. Dopamine has been related to the normal learning of stimuli with behavioral and motivational significance, attention, and most importantly the reward system. In accordance with the role of dopamine in reward processing, addictive drugs stimulate dopamine release. Although the exact mechanism has yet to be elucidated, the role of dopamine in the reward system and addiction has been proposed as the origin of DDS. Models of addiction have been used to explain how dopamine replacement therapy produces DDS. One of these models of addiction proposes that over the usage course of a drug there is a habituation to the rewarding that it produces at the initial stages. This habituation is thought to be dopamine mediated. With long-term administration of L-dopa the reward system gets used to it and needs higher quantities. As the user increases drug intake there is a destruction of dopaminergic receptors in the striatum which acts in addition to an impairment in goal-direction mental functions to produce an enhancement of sensitization to dopamine therapy. The behavioral and mood symptoms of the syndrome are produced by the dopamine overdose.

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