Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence.

Considerable evidence suggests that transmission at hypocretin-1 (orexin-1) receptors (Hcrt-R1) plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV) cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg) dose-dependently decreased cocaine (0.5 mg/kg/infusion) self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg) also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg) on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts

Earthquake slip surfaces identified by biomarker thermal maturity within the 2011 Tohoku-Oki earthquake fault zone.

Extreme slip at shallow depths on subduction zone faults is a primary contributor to tsunami generation by earthquakes. Improving earthquake and tsunami risk assessment requires understanding the material and structural conditions that favor earthquake propagation to the trench. We use new biomarker thermal maturity indicators to identify seismic faults in drill core recovered from the Japan Trench subduction zone, which hosted 50 m of shallow slip during the Mw9.1 2011 Tohoku-Oki earthquake. Our results show that multiple faults have hosted earthquakes with displacement ≥ 10 m, and each could have hosted many great earthquakes, illustrating an extensive history of great earthquake seismicity that caused large shallow slip. We find that lithologic contrasts in frictional properties do not necessarily determine the likelihood of large shallow slip or seismic hazard

Modelling the atomic structure of very high-density amorphous ice

The structure of very high-density amorphous (VHDA) ice has been modelled by positionally disordering three crystalline phases, namely ice IV, VI and XII. These phases were chosen because only they are stable or metastable in the region of the ice phase diagram where VHDA ice is formed, and their densities are comparable to that of VHDA ice. An excellent fit to the medium range of the experimentally observed pair-correlation function g(r) of VHDA ice was obtained by introducing disorder into the positions of the H2O molecules, as well as small amounts of molecular rotational disorder, disorder in the O--H bond lengths and disorder in the H--O--H bond angles. The low-k behaviour of the experimental structure factor, S(k), is also very well reproduced by this disordered-crystal model. The fraction of each phase present in the best-fit disordered model is very close to that observed in the probable crystallization products of VHDA ice. In particular, only negligible amounts of ice IV are predicted, in accordance with experimental observation.Comment: 4 pages, 3 figures, 1 table, v2: changes made in response to referees' comments, the justification for using certain ice phases is improved, and ice IV is now disordered as wel

Re Int\u27l Union of Electrical Workers, Local 510, and Phillips Cables Ltd

Employee Grievance alleging improper lay-off. The facts: A statement of the facts upon which this grievance arose has been agreed to by the parties. At approximately 3:30 p.m. on October 5, 1967, a power inter­ruption cut off the supply of water to a portion of the company\u27s Brockville plant and the company was informed that this situ­ation was not likely to be corrected before morning. The compa­ny therefore, at 6 p.m. on October 5, 1967, sent home four tuber operators whose machines were affected by reduced air pressure. These operators were the grievors John Link, W. Skelton, James Donaghue and Karl Frohle. At 8 p.m. on the same day, because the work on the sparkers and winders came from the machines of the four employees mentioned, five other employees, three sparker operators, one winder operator and one clerk were sent home

Re National Harbours Board and Public Service Alliance of Canada

Employee Grievance alleging unjust discharge. AWARD: Employee grievance alleging breach of a collective agree­ment between the parties dated August 15, 1973, in that the grievor was discharged without just cause because the medical reasons for his discharge are not supported by the evidence. At the hearing it was also argued on behalf of the grievor, that his grievance should be allowed because he did not receive fair notice of the grounds upon which his employ­ment was terminated. The grievor requests that he be rein­stated in his position as constable with the National Harbour Police, with full pay and benefits retroactive to the date of his release. He further requests that all reference to this action be purged from the National Harbours Board\u27s and Government\u27s files

Dynamic detection of electron spin accumulation in ferromagnet-semiconductor devices by ferromagnetic resonance

A distinguishing feature of spin accumulation in ferromagnet-semiconductor devices is precession of the non-equilibrium spin population of the semiconductor in a magnetic field. This is the basis for detection techniques such as the Hanle effect, but these approaches become less effective as the spin lifetime in the semiconductor decreases. For this reason, no electrical Hanle measurement has been demonstrated in GaAs at room temperature. We show here that by forcing the magnetization in the ferromagnet (the spin injector and detector) to precess at the ferromagnetic resonance frequency, an electrically generated spin accumulation can be detected from 30 to 300 K. At low temperatures, the distinct Larmor precession of the spin accumulation in the semiconductor can be detected by ferromagnetic resonance in an oblique field. We verify the effectiveness of this new spin detection technique by comparing the injection bias and temperature dependence of the measured spin signal to the results obtained using traditional methods. We further show that this new approach enables a measurement of short spin lifetimes (< 100 psec), a regime that is not accessible in semiconductors using traditional Hanle techniques.Comment: 4 figure