PDE4 inhibition enhances hippocampal synaptic plasticity in vivo and rescues MK801-induced impairment of long-term potentiation and object recognition memory in an animal model of psychosis

Inhibition of phosphodiesterase type 4 (PDE4) by rolipram (4-(3-(cyclopentyloxy)-4-methoxyphenyl)-pyrrolidin-2-one) has been the focus of many behavioral and molecular studies in the recent years. Rolipram exhibits memory-enhancing effects in rodents. In vitro studies have shown that long-term potentiation (LTP), which may comprise a cellular substrate for learning, is also enhanced by rolipram. However, effects have not been assessed in vivo. Rolipram has antipsychotic properties. Psychosis affects cognition and in animal models of psychosis LTP is impaired. In this study, we investigated if PDE4 inhibition improves LTP in healthy animals in vivo and if PDE4 inhibition rescues impaired LTP and prevents object recognition memory deficits in an animal model of psychosis. Recordings were made from the hippocampus of adult, freely behaving Wistar rats. Thirty minutes after treatment with rolipram or vehicle, a tetanus was applied to the medial perforant path to elicit short-term potentiation (STP) in the dentate gyrus. At this time-point, radioimmunoassay revealed that rolipram significantly elevated cyclic adenosine monophosphate levels in the dorsal hippocampus, in line with reports by others that rolipram mediates decreased PDE4 activity. In healthy animals, both intracerebroventricular and subcutaneous treatment with rolipram facilitated STP into LTP, suggesting that PDE4 inhibition may have a permissive role in plasticity mechanisms that are relevant for learning and memory. One week after a single systemic treatment with the irreversible N-methyl--aspartate antagonist, MK801, LTP and object recognition memory were significantly impaired, but could be rescued by PDE4 inhibition. These data suggest that the relief of cognitive disturbances in psychosis models by rolipram may be mediated in part by a rescue of hippocampal LTP

Service Systems in Changing Paradigms: An Inquiry Through the Systems Sciences

For professionals at the beginning of the 21st century, much of the conventional wisdom on business management and engineering is founded in the 20th century industrial / manufacturing paradigm. In developed economies, however, the service sector now dominates the manufacturing sector, just as manufacturing prevailed over the agricultural sector after the industrial revolution.\ud This chapter proposes the development of a body of knowledge on services systems, based on foundations in the systems sciences. The approach includes the design of\ud the systems of inquiry, acknowledging that body of knowledge on 21st century service systems is relatively nascent. A program of action science is proposed, with an\ud emphasis on multiple realities and knowledge development through dialectic. The outcome pursued is an increased number of T-shaped people with depth and breadth\ud in service systems, in communities of inquiry of researchers and practitioners

Backward integration and collusion in a duopoly model with asymmetric costs

Backward integration, Collusion, Duopoly, L42, L12,