Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys

The chemogenetic technology designer receptors exclusively activated by designer drugs (DREADDs) afford remotely reversible control of cellular signaling, neuronal activity and behavior. Although the combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities and potential off-target effects of CNO represent areas for improvement. Here, we provide a new high-affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 μg per kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 μg per kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents a potent, selective, metabolically stable and fast-acting DREADD agonist with utility in both mice and nonhuman primates for a variety of applications

Institutionalising CSR in Colombia’s extractive sector: disciplining society, destabilising enforcement?

This article analyses the institutionalisation of corporate social responsibility (CSR) in the context of resource extraction in Colombia and the use of human rights language in this normative project. We argue that “rights-based” CSR constructs a new “public–private reason of state” that has disciplinary implications for Colombian society and might contribute to destabilising existing regimes of rights enforcement. Rather than reconciling human rights imperatives and market forces, we conclude, CSR institutionalisation might best be conceptualised as the result of powerful groups strategically harnessing the forces of globalisation