Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol

Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse

Balance Between Projecting Neuronal Populations of the Nucleus Accumbens Controls Social Behavior in Mice

International audienceBACKGROUND: Deficient social interactions are a hallmark of major neuropsychiatric disorders, and accumulating evidence points to altered social reward and motivation as key underlying mechanisms of these pathologies. In the present study, we further explored the role of the balance of activity between D 1 and D 2 receptor-expressing striatal projection neurons (D1R-and D2R-SPNs) in the control of social behavior, challenging the hypothesis that excessive D2R-SPN activity, rather than deficient D1R-SPN activity, compromises social behavior.METHODS: We selectively ablated D1R-and D2R-SPNs using an inducible diphtheria toxin receptor-mediated cell targeting strategy and assessed social behavior as well as repetitive/perseverative behavior, motor function, and anxiety levels. We tested the effects of optogenetic stimulation of D2R-SPNs in the nucleus accumbens (NAc) and pharmacological compounds repressing D2R-SPN. RESULTS: Targeted deletion of D1R-SPNs in the NAc blunted social behavior in mice, facilitated motor skill learning, and increased anxiety levels. These behaviors were normalized by pharmacological inhibition of D2R-SPN, which also repressed transcription in the efferent nucleus, the ventral pallidum. Ablation of D1R-SPNs in the dorsal striatum had no impact on social behavior but impaired motor skill learning and decreased anxiety levels. Deletion of D2R-SPNs in the NAc produced motor stereotypies but facilitated social behavior and impaired motor skill learning. We mimicked excessive D2R-SPN activity by optically stimulating D2R-SPNs in the NAc and observed a severe deficit in social interaction that was prevented by D2R-SPN pharmacological inhibition.CONCLUSIONS: Repressing D2R-SPN activity may represent a promising therapeutic strategy to relieve social deficits in neuropsychiatric disorders

Measurement of the mass of the Z boson and the energy calibration of LEP

In 1985 the French government created a unique circuit for the dissemination of doctoral theses: References went to a national database “Téléthèses” whereas the documents were distributed to the university libraries in microform. In the era of the electronic document this French network of deposit of and access to doctoral theses is changing. How do you discover and locate a French thesis today, how do you get hold of a paper copy and how do you access the full electronic text? What are the catalogues and databases referencing theses since the disappearance of “Téléthèses”? Where are the archives, and are they open? What is the legal environment that rules the emerging structures and tools? This paper presents national plans on referencing and archiving doctoral theses coordinated by the government as well as some initiatives for creating full text archives. These initiatives come from universities as well as from research institutions and learned societies. “Téléthèses” records have been integrated in a union catalogue of French university libraries SUDOC. University of Lyon-2 and INSA Lyon developed procedures and tools covering the entire production chain from writing to the final access in an archive: “Cyberthèses” and “Cither”. The CNRS Centre for Direct Scientific Communication at Lyon (CCSD) maintains an archive (“TEL”) with about 2000 theses in all disciplines. Another repository for theses in engineering, economics and management called “Pastel” is proposed by the Paris Institute of Technology (ParisTech), a consortium of 10 engineering and commercial schools of the Paris region