MDMA modulates spontaneous firing of subthalamic nucleus neurons in vitro.

3,4-Methylene-dioxy-N-methylamphetamine (MDMA, 'ecstasy') has a broad spectrum of molecular targets in the brain, among them receptors and transporters of the serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic systems. Its action on the serotonergic system modulates motor systems in rodents and humans. Although parts of the basal ganglia could be identified as mediators of the motor effects of MDMA, very little is known about the role of the subthalamic nucleus (STN). Therefore, this study investigated the modulation of spontaneous action potential activity of the STN by MDMA (2.5-20 µM) in vitro. MDMA had very heterogeneous effects, ranging from a complete but reversible inhibition to a more than twofold increase in firing at 5 µM. On average, MDMA excited STN neurons moderately, but lost its excitatory effect in the presence of the 5-HT(2A) antagonist MDL 11,939. 5-HT(1A) receptors did not appear to play a major role. Effects of MDMA on transporters for serotonin (SERT) and norepinephrine (NET) were investigated by coapplication of the reuptake inhibitors citalopram and desipramine, respectively. Similar to the effects of 5-HT(2A) receptor blockade, antagonism of SERT and NET bestowed an inhibitory effect on MDMA. From these results, we conclude that both the 5-HT and the noradrenergic system mediate MDMA-induced effects on STN neurons.

A time-efficient screening tool for activities of daily living functions in Parkinson's disease dementia.

INSTRUCTION: In Parkinson's disease (PD), activities of daily living (ADL) impairments are crucial for diagnosis of dementia (PDD). Performance-based tests are promising tools to discriminate between different levels of cognitive impairment in PD; however, the value of those tests for diagnosis of PDD is only sparsely investigated. Therefore, we evaluated the Erlangen Test of Activities of Daily Living (E-ADL), a time-efficient performance-based ADL test, in PD. METHOD: In this cross-sectional study, 40 PD patients with normal cognition (PD-NC), 45 patients with mild cognitive impairment (PD-MCI) and 21 patients with PDD were assessed with a comprehensive ADL and cognitive test battery. RESULTS: Interrater reliability (rs =.86) indicated high consistency of the standardized E-ADL scoring system between raters. The E-ADL correlated significantly with other tests of ADL functions (p <.01), highest with an alternative performance-based ADL test (rs = -.52), and lowest with self-ratings and a physician-rated scale. The E-ADL was also associated with cognitive impairment (p <.01), but also with motor impairment. A binary logistic regression model verified that the E-ADL (p =.04) was an independent predictor of PDD, in addition to motor impairment explaining 53.3% of variance. Receiver operating characteristic curve analysis of the E-ADL revealed an area under the curve of 0.78, a specificity of 77%, and a sensitivity of 67% for diagnosis PDD. CONCLUSIONS: The standardized, easy, and quick to administer E-ADL showed acceptable levels of reliability, and validity in PD and measures cognitive-driven ADL functions. Therefore, it might be a suitable test to support diagnosis of PDD in the clinical daily routine.