In patients with Parkinson disease (PD), impulse control disorders (ICDs) such as hypersexuality and pathologic gambling and shopping can be devastating complications of antiparkinsonian treatment. To improve their detection, we investigated clinical features associated with ICDs. Subjects were participants in a longitudinal study of PD. ICDs were associated with use of dopamine agonists and depressed mood, disinhibition, irritability, and appetite disturbance.
"There is growing evidence that psychosis and impulse control disorders develop in patients under L-DOPA and dopamine agonist therapy (Pontone et al., 2006; Voon et al., 2006; Struhal et al., 2012). A number of preclinical studies also show that long-term administration of dopamine agonists, as well as L-DOPA, is rewarding and reinforcing and may elicit psychosis-like behavior (Tomiyama et al., 2005; Marston et al., 2009; Ikram and Haleem, 2011; Kotagale et al., 2012; Mahmood et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: Dysfunctions of the basal ganglia are associated with a number of neurological and psychiatric conditions including Parkinson's disease and schizophrenia. Current treatments of these disorders are mostly symptomatic and inadequate, and are often associated with a number of unwanted side-effects. The striatum, the terminal region of the nigrostriatal dopamine pathway, is the main input nucleus of the basal ganglia, and dopamine neurotransmission through the nigrostriatal pathway plays a crucial role in the modulation of basal ganglia output and mediated behaviors. Evidence suggests a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in the modulation of dopamine neurotransmission and in improving pharmacotherapy in schizophrenia and Parkinson's disease. This review concerns the role of 5-HT1A receptors in the modulation of nigrostriatal dopamine neurotransmission, with the aim of providing guidelines for future research to improve pharmacotherapy. The current state of knowledge suggests that drugs simultaneously targeting dopamine D2 and 5-HT1A receptors may improve pharmacotherapy for schizophrenia and Parkinson's disease. Activation of somatodendritic 5-HT1A receptors in the dorsal raphe nucleus has an important role in the alleviation of extrapyramidal symptoms and levodopa-induced dyskinesia induced by antipsychotic treatment. Drugs acting exclusively through dopamine D2 and 5-HT1A receptors are highly needed to validate the potential role of 5-HT1A receptors in improving therapeutics for Parkinson's disease and schizophrenia.
"Enhanced ventral striatal dopamine release due to hypersensitization of the ventral striatal circuitry may be another explanation (Evans et al., 2006). Complex interactions between DAs and dopamine receptor subtypes may lead to the development of ICDs in PD patients (Pontone et al., 2006). DAs, such as pramipexole and ropinirole, have remarkably specific binding affinities with D3 receptor (Gerlach et al., 2003), which are at least 100-fold greater than with D2 or D1 receptor. "
[Show abstract][Hide abstract] ABSTRACT: Background: Impulsive and compulsive behaviors (ICBs) are a heterogeneous group of conditions that may be caused by long-term dopaminergic replacement therapy (DRT) of Parkinson’s disease (PD). The spectrum of ICBs includes dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs).
Contents: We made a detailed review regarding the epidemiology, pathology, clinical characteristics, risk factors, diagnosis as well as treatment of ICBs.
Results: The prevalence of ICBs in PD patients is approximately 3–4% for DDS, 0.34–4.2% for punding, and 6–14% for ICDs, with higher prevalence in Western populations than in Asian. Those who take high dose of levodopa are more prone to have DDS, whereas, ICDs are markedly associated with dopamine agonists. Different subtypes of ICBs share many risk factors such as male gender, higher levodopa equivalent daily dose, younger age at PD onset, history of alcoholism, impulsive, or novelty-seeking personality. The Questionnaire for Impulsive–Compulsive Disorder in Parkinson’s Disease-Rating Scale seems to be a rather efficacious instrument to obtain relevant information from patients and caregivers. Treatment of ICBs is still a great challenge for clinicians. Readjustment of DRT remains the primary method. Atypical antipsychotics, antidepressants, amantadine, and psychosocial interventions are also prescribed in controlling episodes of psychosis caused by compulsive DRT, but attention should be drawn to balance ICBs symptoms and motor disorders. Moreover, deep brain stimulation of the subthalamic nucleus might be a potential method in controlling ICBs.
Conclusion: The exact pathophysiological mechanisms of ICBs in PD remains poorly understood. Further researches are needed not only to study the pathogenesis, prevalence, features, and risk factors of ICBs, but to find efficacious therapy for patients with these devastating consequences.
"While apomorphine and other dopamine receptor agonists act positively in partially restoring the motor deficits elicited by Parkinson's disease, a constellation of addictive syndromes has been also noticed in certain patients. It includes addiction to medications, compulsive behaviors, and disturbances of impulse control (Struhal et al., 2012; Pontone et al., 2006, Voon et al., 2006; Weintraub et al., 2010) Preclinical research also shows that dopamine agonists including apomorphine are rewarding when tested in conditioned place preference (CPP) paradigm (Papp, 1988; Khroyan et al., 1995; Hoffman et al., 1988, Graham et al., 2007; Zengin- Toktas et al., 2013). Development of novel pharmacological agents for the suppression of rewarding effects of apomorphine and other dopamine agonists is therefore important for improving therapeutics in Parkinson's disease (Haleem, 2013). "
[Show abstract][Hide abstract] ABSTRACT: Apomorphine is a non-narcotic derivative of morphine, which acts as a dopamine agonist to produce psychostimulant like effects. Currently, apomorphine is used in patients with advanced Parkinson's disease, for the treatment of persistent and disabling motor fluctuations, but a constellation of addictive syndromes such as excessive over use of medication, compulsive behaviors, and disturbances of impulse control are noticed in certain patients. Research on rodent models using conditioned place preference (CPP) paradigm also shows that the drug is rewarding. Previously we have shown that repeated administration of apomorphine produces behavioral sensitization which is prevented in rats co-injected with a low (1.0 mg/kg) but not higher (2.0 mg/kg) dose of buspirone. The present study shows that rewarding effects of apomorphine (1.0 mg/kg) in a CPP paradigm are also blocked in rats co-injected with a low (1.0 mg/kg) but not higher (2.0 mg/kg) dose of buspirone. The levels of serotonin and its metabolite are decreased in the caudate as well as nucleus accumbens of rats exhibiting CPP and the decreases do not occur in animals co-injected with low or higher dose of buspirone. The levels of dopamine and its metabolites are not affected in animals exhibiting CPP; administration as well as co-administration of higher dose of buspirone decreased dopamine metabolism in the caudate as well as nucleus accumbens. The findings suggest a critical role of serotonin in the rewarding effects of apomorphine and imply that co-use of buspirone at low doses can help to control addictive syndromes in Parkinson's disease patients on apomorphine therapy.
Brain Research 10/2014; 1586. DOI:10.1016/j.brainres.2014.06.022 · 2.84 Impact Factor
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