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A small proportion of patients with Parkinson's disease (PD), chronically under dopamine replacement therapy, may undergo an addiction-like behavioral disturbance, named dopamine dysregulation syndrome (DDS). This behavioral disorder is characterized by the increase of doses beyond those required for motor control, and its management remains difficult; thus, early recognition and careful monitoring of at-risk individuals are crucial. We report the cases of two PD patients with a previous unsatisfactory switching from an immediate release (IR) to an extended release (ER) pramipexole formulation who developed DDS. PD patients unsatisfactorily switched from an IR to an ER formulation of dopamine agonists should be considered as at-risk individuals for DDS development.

Background: Parkinson's disease (PD) occurs more frequently in men than in women and a higher risk for PD development in males compared with females has been hypothesized, suggesting gender may be a significant factor in the development and progression of parkinsonism. To date, gender differences in non-motor symptoms are under-reported., Objective: To assess gender differences in motor and non-motor symptoms among Sardinian PD patients., Methods: One hundred fifty-six (91 male and 65 female) consecutive Sardinian PD outpatients were included in this analysis. Modified Hoehn and Yahr scale and UPDRS were used to assess motor symptoms, while non-motor disturbances were evaluated with the non-motor symptoms scale (NMSS). Presence of depression, anxiety and other iatrogenic behavioral disorders was also investigated. In order to determine how gender differences could be specific to PD, 132 age-matched normal controls were assessed with the NMSS., Results: Women were more likely than men to present with tremor as initial symptom (p<.025) and worse UPDRS instability score (p<.02). NMSS score in females was significantly higher than that in males (p<.018). A significantly higher severity in cardiovascular (p<0.002), sleep/fatigue (p<.018) and mood/apathy (p<.001) domains was observed in female PD patients, while the sexual dysfunction domain was reported with a significantly higher score in male patients (p<.017). Fatigue (p<.03), lack of motivation (p<.015) and sadness (p<.009) were observed significantly more frequent in females, while altered interest in sex was noted as more common in males (p<.001). Frequency of depression (p<.011) and anxiety (p<.001) was significantly higher in females, while male patients had increased frequency of compulsive sexual behaviors (p<.05). There was a significantly higher frequency of non-motor symptoms in eight domains in both male and female PD patients compared with controls (p<.001, for all comparisons, with the exception of urinary disturbances in females: p<.004). Only sexual dysfunctions were not significantly higher in male and female PD patients compared with controls., Discussion: The present study highlights the role of gender differences associated with the occurrence of motor and non-motor disorders and our findings indicate that spectrum and severity of non-motor symptoms may present with different gender distribution in PD patients, suggesting a possible sex-related effect., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25mg/kg, SC) and d-amphetamine (AMPH, 2.5mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10μg/1μl) and in the nucleus accumbens (NAc) shell and core (0.5μg/0.5μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region., (Copyright © 2011 Elsevier Ltd. All rights reserved.)