The present study aimed to characterize a functional role for group I metabotropic glutamate receptors (mGluRs) in the nucleus accumbens and the capacity of repeated cocaine to elicit long-term changes in group I mGluR function. Reverse dialysis of the group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) into the nucleus accumbens resulted in an increase in extracellular glutamate levels that was mediated by the mGluR1 subtype and depended on voltage-dependent Na(+) and Ca(2+) conductance. At 3 weeks after discontinuing 1 week of daily cocaine injections, the capacity of DHPG to induce glutamate release was markedly reduced. Similarly, DHPG induced an mGluR1-dependent increase in locomotor activity after microinjection into the nucleus accumbens that was significantly blunted 3 weeks after repeated cocaine administration. Signaling through group I mGluRs is regulated, in part, by Homer proteins, and it was found that the blunting of group I mGluR-induced glutamate release and motor activity after repeated cocaine was associated with a reduction in Homer1b/c protein that was selective for the medial nucleus accumbens. These data show that repeated cocaine produces an enduring inhibition of the neurochemical and behavioral consequences of stimulating mGluR1 that is accompanied by changes in the mGluR scaffolding apparatus.

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The successful design and delivery of oil and gas production wells require significant levels of collaboration across multiple domains. The challenges encountered vary widely, and including risk evaluations from offset well analysis, domain-specific workflows and practices, geological concerns and limitations, engineering technology of choice, cost considerations, as well as environmental and safety concerns. Suboptimal levels of collaboration among team members, such as managers, geoscientists, drilling engineers, mud engineers, directional drillers, suppliers, and consultants, often negatively impact the quality or cost of the well. The application and analysis of a cloud technology in a case study shows how the cost of well planning can be significantly reduced, which enhances team collaboration and improves the process of engineering design. The digital well construction planning solution enables oil and gas operators to manage projects easily by: simplifying task assignment among drilling and operations team members, improving process status tracking, documenting the historical progress of each task, and opening access to industry-leading workflows and engines. This digital well construction planning solution which is deployed in the cloud, includes a project management structure, aiding with the assignment, review, and approval of tasks. Geoscientists and engineers can log in to the digital well construction planning solution, finish specific tasks, and then share the completed tasks with the rest of the project. This enables other team members whose design considerations have dependencies to incorporate holistic and representative design criteria into their own workflows. The process is smooth, concurrent, and evergreen, and all tasks are shared at both the output level and the engineering level. This approach ensures that the project data, workflows, and engineering analysis are always current. With this new solution, well planning time can be reduced from several days to a few hours. The project manager can easily track the status of each task without back-and-forth phone conversations or e-mails. With unconventional wells, where the well designs are often similar in the same region, template and project copy functions can be used to duplicate designs to the next well and accelerate the design process. After a project copy or template import is executed for a new project, the engineering validations can be produced after being shared. Trajectories can be designed automatically, incorporating anti-collision considerations, geological targets, well surface locations, and other design constraints. Then, well hydraulics, torque and drag analysis, bottomhole assembly (BHA) tendencies, and casing designs are validated to make sure the well is drillable and cost-effective. This digital well construction planning solution can help operators deliver safe, cost-effective wells on time, and execute high-quality well planning.

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