In particular, two initial experiments in PD patients with intermediate disease stages showed that apomorphine lengthens reaction times during working memory and increases the latency of event-related potentials during an odd-ball task (Ruzicka et al. 1994; Costa et al. 2003). In contrast, two later studies in patients with more advanced forms of PD reported no effect of apomorphine infusion #buy SB1518 randurls[1|1|,|CHEM1|]# on a series of neuropsychological tests (Alegret et al. 2004; De Gaspari et al. 2006). Our hypothesis was that the action of apomorphine Inhibitors,research,lifescience,medical on striatal responses associated with working memory depends on the level of nigrostriatal degeneration, which we quantified via DAT

imaging. Given the inverted-U-shaped relation between dopaminergic neurotransmission and PFC function, we also hypothesized that brain responses to apomorphine followed a nonlinear model (Williams and Goldman-Rakic 1995; Arnsten and Goldman-Rakic Inhibitors,research,lifescience,medical 1998). In particular, apomorphine was expected to overdose VTA–PFC circuits in patients with less severe dopaminergic deficit, as recently proposed by a staging model of cognitive deficits in PD (de la Fuente-Fernandez 2012). Participants and Methods Participants Sixteen PD patients and 13 sex-, education-, Inhibitors,research,lifescience,medical and age-matched healthy controls (HCs; no neuropsychiatric diseases and normal

structural MRI of the brain) gave their written informed consent to participate in this study, approved by the Ethics Board of the University “Magna Graecia” of Catanzaro. A junior (M. S.) and a senior (A. Q.) neurologist, both blind to other results, made the diagnosis of PD Inhibitors,research,lifescience,medical in accordance to the United Kingdom Parkinson’s Disease Society Brain Bank criteria (Hughes et al. 1992). Age of onset, disease duration, and severity of symptoms, as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn–Yahr stage, were recorded. Additional inclusion criteria for PD patients were (1) no dementia according to the DSM-IV (American Psychiatric Association 1994), (2) no use of psychoactive drugs (e.g., benzodiazepines,

antidepressants) during 1 month Inhibitors,research,lifescience,medical preceding the experiment, (3) no use of caffeine within 24 h before the experiment, (4) no history of smoking, (5) no major depression according to the DSM-IV criteria (American Psychiatric Association 1994), (6) right handedness, as assessed by the Edinburgh Handedness Inventory already (Oldfield 1971), and (7) normal structural MRI of the brain. In all participants, a trained neuropsychologist (C. C.) collected the following neuropsychological measures: (1) executive control (Frontal Assessment Battery, Modified Card Sorting Test) (Nelson 1976; Iavarone et al. 2004), (2) short- and long-term verbal memory (Rey Auditory Verbal Learning Test; Rey 1958), (3) attention and working memory (Digit Span Forward and Backward; Wechsler 1981), (4) verbal fluency and language comprehension (Controlled Oral Word Association Test, Token Test; De Renzi and Vignolo 1962; Benton et al.