A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Robot shift from industrial production to social reproduction

This chapter analyses people\u2019s attitudes towards the use of robots in the different domains of life and, specifically, in the domain of social reproduction. The analysis is based on Eurobarometer 382 \u201cPublic Attitudes towards Robots\u201d data (N = 26,751), which was carried out among EU citizens aged 15 and over in 27 member states in 2012. The results of the study show that on average European perceptions of robots are positive and permissive. The life domains in which robots have already been used for a long time (e.g. space exploration, manufacturing, military and security business, search and rescue work) turn out to be the most popular areas for the further penetration of robots. The least preferred life domains are those, which address the core functions of social reproduction (e.g. care of children, elderly people and the disabled, education, leisure). With a series of ordinal logistic regression analyses, we outline the socio-demographic factors that are associated with the willingness to have more robots in the various fields of social production. Pensioner\u2019s supportive attitude towards the use of robots in health care and educational activities is highlighte

Fun and friends : the impact of workplace fun and constituent attachment on turnover in a hospitality context

Extending the growing body of research on fun in the workplace, this article reports on a study examinining the relationship between fun and employee turnover. Specifically, this research focused on the influence of three forms of fun on turnover – fun activities, coworker socializing and manager support for fun. With a sample of 296 servers from 20 units of a national restaurant chain in the US, coworker socializing and manager support for fun were demonstrated to be significantly related to turnover. In addition, constituent attachment was found to mediate the relationship between each of the three forms of fun and turnover. This research highlights that not all types of fun are equal and demonstrates that one of the key means through which fun influences retention is by facilitating the development of high quality work relationships