Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Agonist. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions

Abstract: 1. In order to explore potential therapeutic implications of cannabinoid antagonists, the effects of the prototypical cannabinoid antagonist SR141716A on monoamine efflux from the medial prefrontal cortex and the nucleus accumbens of the rat were investigated by in vivo microdialysis. 2. SR141716A moderately increased serotonin efflux and concentrations of its metabolite 5-HIAA, both in the medial prefrontal cortex and the nucleus accumbens, and increased norepinephrine, dopamine and their metabolites in the medial prefrontal cortex. In contrast, it had no effect on norepinephrine, dopamine and their metabolites in the nucleus accumbens. 3. At the same doses, SR141716A increased acetylcholine efflux in the medial prefrontal cortex, in agreement with previous studies; contrary to the effects in cortex, SR141716A had no effect on acetylcholine efflux in the nucleus accumbens. 4. The efficacy of SR141716A in the psychostimulant-induced hyperlocomotion and the forced swimming paradigms was also explored in mice. SR141716A attenuated phenylcyclidine- and d-amphetamine-induced hyperlocomotion, without affecting locomotor activity when administered alone, and decreased immobility in the forced swimming test. 5. These results suggest that the cortical selectivity in the release of catecholamines, dopamine in particular, induced by the cannabinoid antagonist SR141716A, its procholinergic properties, together with its mild stimulatory effects on serotonin and norepinephrine efflux make similar compounds unique candidates for the treatment of psychosis, affective and cognitive disorders.

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions.

Abstract: The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).