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- Borroto-Escuela, DO, et al.
(author)
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OSU-6162, a Sigma1R Ligand in Low Doses, Can Further Increase the Effects of Cocaine Self-Administration on Accumbal D2R Heteroreceptor Complexes
- 2020
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In: Neurotoxicity research. - : Springer Science and Business Media LLC. - 1476-3524 .- 1029-8428. ; 37:2, s. 433-444
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Journal article (peer-reviewed)abstract
- Cocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer (–) OSU-6162 (OSU-6162) with a nanomolar affinity for the Sigma1R can acutely modulate in low doses the effects of cocaine self-administration. In behavioral studies, OSU-6162 (5 mg/kg, s.c.) did not significantly change the number of active lever pressing and cocaine infusions. However, a trend to reduce cocaine readouts was found after 3 days of treatment. In contrast, in maintenance of cocaine self-administration, the proximity ligation assay performed on brains from rats pretreated with OSU-6162 showed highly significant increases in the density of the D2R-Sigma1R heteroreceptor complexes in the shell of the nucleus accumbens versus OSU-6162 induced increases in this region of yoked saline rats. In cocaine self-administration, highly significant increases were also induced by OSU-6162 in the A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell versus vehicle-treated rats. Furthermore, ex vivo, the A2AR agonist CGS21680 (100 nM) produced a marked and significant increase of the D2R Ki high values in the OSU-6162-treated versus vehicle-treated rats under maintenance of cocaine self-administration. These results indicate a substantial increase in the inhibitory allosteric A2AR-D2R interactions following cocaine self-administration upon activation by the A2AR agonist ex vivo. The current results indicate that OSU-6162 via its high affinity for the Sigma1R may increase the number of accumbal shell D2R-Sigma1R and A2AR-D2R heteroreceptor complexes associated with further increases in the antagonistic A2AR-D2R interactions in cocaine self-administration.
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- Colegrove, P., et al.
(author)
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Welding process impact on residual stress and distortion
- 2009
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In: Science and Technology of Welding and Joining. - 1362-1718. ; 14:8, s. 717-725
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Journal article (peer-reviewed)abstract
- Residual stress and distortion continue to be important issues in shipbuilding and are still subject to large amounts of research. This paper demonstrates how the type of welding process influences the amount of distortion. Many shipyards currently use submerged arc welding (SAW) as their welding process of choice. In this manuscript, the authors compare welds made by SAW with DC gas metal arc welding, pulsed gas metal arc welding, Fronius cold metal transfer (CMT), autogenous laser and laser hybrid welding on butt welds in 4 mm thick DH36 ship plate. Laser and laser hybrid welding were found to produce the lowest distortion. Nevertheless, a considerable improvement can be achieved with the pulsed gas metal arc welding and CMT processes. The paper seeks to understand the relationship between heat input, fusion area, measured distortion and the residual stress predicted from a simple numerical model, and the residual stresses validated with experimental data.
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