Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism.

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood, and new effective pharmacological treatments are desired. Here, using a bidirectional neuromodulation approach, we demonstrate a causal link between reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. A neuron-specific prefrontal mGluR2 knockdown in rats generated a phenotype of reduced cognitive flexibility and excessive alcohol seeking. Conversely, virally restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. In the search for a pharmacological intervention with high translational potential, psilocybin was capable of restoring mGluR2 expression and reducing relapse behavior. Last, we propose a FDG-PET biomarker strategy to identify mGluR2 treatment-responsive individuals. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving and provided a personalized mGluR2 mechanism-based intervention strategy for medication development for alcoholism.

Cold stress signalling in female reproductive tissues.

Cold stress is a significant threat for plant productivity and impacts on plant distribution and crop production, particularly so when it occurs during the growth phase. A developmental stage at risk is that of flowering, since a single stress event during sensitive stages, such as the full-bloom stage of fruit trees can be fatal for reproductive success. Although pollen development and fertilization are widely viewed as the most critical reproductive phases, the development and function of female reproductive tissues, which in Angiosperms are embedded in the gynoecium, are also affected by cold stress. Today however, we have essentially no understanding of the cold stress response pathways that act during floral organogenesis. In this review, we briefly summarize our current knowledge of cold stress signalling modules active in vegetative tissues that may provide a framework of general principles also transferable to female reproductive tissues. We then align these signalling cascades with those that govern gynoecium development to identify factors that may act in both processes and could thereby contribute to cold stress responses in female reproductive tissues.