%0 Journal Article
%T Dopamine Agonists and Pathologic Behaviors
%A Brendan J. Kelley
%A Andrew P. Duker
%A Peter Chiu
%J Parkinson's Disease
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/603631
%X The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson¡¯s disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics. 1. Introduction An association between neurodegeneration of the dopaminergic nigrostriatal system and the major motor symptoms of Parkinson¡¯s disease (PD) was first recognized in 1960 [1] after pioneering work by Arvid Carlsson showed that L-DOPA reversed the parkinsonian syndrome in rabbits induced by reserpine [2]. This observation led to the first trials of injected levodopa (L-dopa), a direct metabolic precursor of dopamine, to address motor symptoms associated with the disease. This treatment demonstrated transient success, but was impractical due to severe toxicities associated with the injections. Gradual titration of oral L-dopa was better tolerated, but was still associated with severe nausea and the requirement of higher doses of L-dopa due to peripheral consumption of the substrate. In the 1970s, compounding L-dopa with the peripheral dopa-decarboxylase inhibitor carbidopa very successfully addressed these shortcomings. Nausea and vomiting were reduced to such a degree that the medication adopted the trade name Sinemet (sine£¿=£¿without; emet = emesis). Compounded levodopa-carbidopa remains the mainstay of treatment for PD. Dopaminergic agonists are synthetic analogues of dopamine. Apomorphine was suggested for the treatment of PD as early as 1884 [3], although the first article describing its effectiveness was not published until 1951 [4]. Bromocriptine was found to be effective in PD in 1974 [5]. Other
%U http://www.hindawi.com/journals/pd/2012/603631/