Long-term use of opioids for pain management results in rapid development of tolerance and dependence leading to severe withdrawal symptoms. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. This study was designed to investigate the involvement of central ET mechanisms in opioid withdrawal. The effect of intracerebroventricular administration of ETA receptor antagonist BQ123 on morphine and oxycodone withdrawal was determined in male Swiss Webster mice. Opioid tolerance was induced and withdrawal was precipitated by the opioid antagonist naloxone. Expression of ETA and ETB receptors, nerve growth factor (NGF), and vascular endothelial growth factor was determined in the brain using Western blotting. BQ123 pretreatment reversed hypothermia and weight loss during withdrawal. BQ123 also reduced wet shakes, rearing behavior, and jumping behavior. No changes in expression of vascular endothelial growth factor, ETA receptors, and ETB receptors were observed during withdrawal. NGF expression was unaffected in morphine withdrawal but significantly decreased during oxycodone withdrawal. A decrease in NGF expression in oxycodone- but not in morphine-treated mice could be due to mechanistic differences in oxycodone and morphine. It is concluded that ETA receptor antagonists attenuate opioid-induced withdrawal symptoms.

The use of rodents to acquire understanding of the function of neural circuits and of the physiological, genetic and developmental underpinnings of behaviour has been constrained by limitations in the scalability, automation and high-throughput operation of implanted wireless neural devices. Here we report scalable and modular hardware and software infrastructure for setting up and operating remotely programmable miniaturized wireless networks leveraging Bluetooth Low Energy for the study of the long-term behaviour of large groups of rodents. The integrated system allows for automated, scheduled and real-time experimentation via the simultaneous and independent use of multiple neural devices and equipment within and across laboratories. By measuring the locomotion, feeding, arousal and social behaviours of groups of mice or rats, we show that the system allows for bidirectional data transfer from readily available hardware, and that it can be used with programmable pharmacological or optogenetic stimulation. Scalable and modular wireless-network infrastructure should facilitate the remote operation of fully automated large-scale and long-term closed-loop experiments for the study of neural circuits and animal behaviour.

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We consider the topic of arrogance from a cross-disciplinary viewpoint. To stimulate further research, we suggest three types of arrogance (individual, comparative, and antagonistic) and six components contributing to them, each logically related to the next. The components progress from imperfect knowledge and abilities to an unrealistic assessment of them, an unwarranted attitude of superiority over other people, and related derisive behavior. Although each component presumably is present to some degree when the next one operates, causality might flow between components in either direction. The classification of components of arrogance should reduce miscommunication among researchers, as the relevant concepts and mechanisms span cognitive, motivational, social, and clinical domains and literatures. Arrogance is an important concept warranting further study for both theoretical and practical reasons, in both psychopathology and normal social interaction. Everyone seems to have qualities of arrogance to some degree, and we consider the importance of arrogance on a spectrum. We contend that humankind can benefit from a better understanding of the cognitive limitations and motivational biases that, operating together, appear to contribute to arrogance. We bring together information and questions that might lead to an invigorating increase in the rate and quality of cross-disciplinary research on arrogance.