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

Tactics of Dispossession: Access, Power, and Subjectivity at the Extractive Frontier

In this article we analyse and theorise how power is exercised and subjectivities reworked to achieve and maintain socio-political order in areas of large-scale international extractive investment. Through a critical review of recent literature on the political ecologies of the international mining and hydrocarbon industries, we explore the strategies that firms and their allies deploy to secure and preserve the transformed relations of land and resource access upon which accumulation relies. Inspired by the work of John Allen we analyse these strategies with attention to the modalities and techniques of power used, highlighting the diverse ways socio-political stability is pursued despite the industry’s destabilising effects. What emerges is that, contrasting the sector’s reputation for coercion and domination, transformed regimes of access to land and resources at the extractive frontier are to a significant degree achieved and stabilised through what Allen calls the ‘quieter registers’ of power. Attention to the varied and overlapping ways extractive firms and their allies exercise power to secure and maintain access to land and resources highlights limitations to David Harvey’s influential accumulation by dispossession framework for understanding how extractive capital circulates into ‘new ground’. It also directs attention to processes of subject formation at the extractive frontier, and to how industry expansion may be facilitated through the production of particular kinds of subjects. To illustrate this, we outline three interrelated ways subjectivities are reworked through peoples’ encounters with the logics, materiality, and power of contemporary extractive industry. We suggest that those living in the shadow of large international extractive operations become extractive subjects