Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application.

Item does not contain fulltextDopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca(2+) channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.1 maart 201

Closing The Marketing Strategy Tactics-Gap: An Institutional Theory Analysis Of Pharmaceutical Value Chain

This chapter identifies a strategy-tactics gap in most previous studies of pharmaceutical marketing, and addresses it by systematically analyzing the marketing strategies used in practice with the help of a unique dataset of court discovery documents unsealed in a recent litigation. Adopting an institutional theory perspective, we examine the dominant logic that underlies pharmaceutical marketing strategies, and contrast it with the organizing logics of the value chain partners. Four distinct marketing strategies with carefully crafted interdependencies emerge from our analysis: (1) market penetration strategy involving a focus on segmentation and penetration, (2) evidence-based strategy involving production of science, (3) medical education strategy involving development and dissemination of standards of care, and (4) surrogate selling strategy involving leverage of peer-to-peer influence among target physicians. Together, the strategies uncovered in our analysis provide coherence to the observed marketing tactics and show that they are largely consistent with the logic of consequences which conflicts with the logic of appropriateness guiding the actions of the value chain partners. The institutional theory analysis shows that: (1) pharmaceutical value chain is characterized by conflicted logics, (2) that are amplified by pharmaceutical marketing strategies thereby, (3) inviting regulatory intervention to constrain and restrict pharmaceutical marketing efforts. We propose an open systems framework that elaborates on value chain interdependencies and compare it with the economic framework that characterizes most current research. We close the chapter with an agenda for future research into the theory and practice of pharmaceutical marketing

The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis

Sifrim-Hitz-Weiss syndrome (SIHIWES) is a recently described multisystemic neurodevelopmental disorder caused by de novo variants in CHD4. In this study, we investigated the clinical spectrum of the disorder, genotype-phenotype correlations, and the effect of different missense variants on CHD4 function