Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats

Abstract RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

Scaling analysis of the unsteady natural convection boundary layer adjacent to an inclined plate for Pr > 1 following instantaneous heating

The unsteady natural convection boundary layer adjacent to an instantaneously heated inclined plate is investigated using an improved scaling analysis and direct numerical simulations. The development of the unsteady natural convection boundary layer following instantaneous heating may be classified into three distinct stages including a start-up stage, a transitional stage and a steady state stage, which can be clearly identified in the analytical and numerical results. Major scaling relations of the velocity and thicknesses and the flow development time of the natural convection boundary layer are obtained using triple-layer integral solutions and verified by direct numerical simulations over a wide range of flow parameters.

4-Aminopyridinium cis-2-carboxycyclohexane-1-carboxylate

In the structure of the title compound, C5H7N2+ C8H11O4-, the cis-monoanions associate through short carboxylic acid-carboxyl O-H...O hydrogen bonds [graph set C(7)], forming zigzag chains which extend along c and are inter-linked through pyridinium and amine N-H...O(carboxyl) hydrogen bonds giving a three-dimensional network structure.

Structural Systematics of the Anhydrous 1:1 Proton-Transfer Compounds of 3,5-Dinitrosalicylic Acid with Aniline and Monosubstituted Anilines

The crystal structures of the proton-transfer compounds of 3,5-dinitrosalicylic acid (DNSA) with a series of aniline-type Lewis bases [aniline, 2-hydroxyaniline, 2-methoxyaniline, 3-methoxyaniline, 4-fluoroaniline, 4-chloroaniline and 2-aminoaniline] have been determined and their hydrogen-bonding systems analysed. All are anhydrous 1:1 salts: [(C6H8N)+(C7H3N2O7)-], (1), [(C6H8NO)+(C7H3N2O7)-], (2), [(C7H10NO)+(C7H3N2O7)-], (3), [(C7H10NO)+(C7H3N2O7)-], (4), [(C6H7FN)+(C7H3N2O7)-], (5), [(C6H7ClN)+(C7H3N2O7)-], (6), and [(C6H9N2)+(C7H3N2O7)-], (7) respectively. Crystals of 1 and 6 are triclinic, space group P-1 while the remainder are monoclinic with space group either P21/n (2, 4, 5 and 7) or P21 (3). Unit cell dimensions and contents are: for 1, a = 7.2027(17), b = 7.5699(17), c = 12.9615(16) Å, α = 84.464(14), β = 86.387(15), γ = 75.580(14)o, Z = 2; for 2, a = 7.407(3), b = 6.987(3), c = 27.653(11) Å, β = 94.906(7)o, Z = 4; for 3, a = 8.2816(18), b = 23.151(6), c = 3.9338(10), β = 95.255(19)o, Z = 2; for 4, a = 11.209(2), b = 8.7858(19), c = 15.171(3) Å, β = 93.717(4)o, Z = 4; for 5, a = 26.377(3), b = 10.1602(12), c = 5.1384(10) Å, β = 91.996(13)o, Z = 4; for 6, a = 11.217(3), b = 14.156(5), c = 4.860(3) Å, α = 99.10(4), β = 96.99(4), γ = 76.35(2)o, Z = 2; for 7, a = 12.830(4), b = 8.145(3), c = 14.302(4) Å, β = 102.631(6)o, Z = 4. In all compounds at least one primary linear intermolecular N+-H…O(carboxyl) hydrogen-bonding interaction is present which, together with secondary hydrogen bonding results in the formation of mostly two-dimensional network structures, exceptions being with compounds 4 and 5 (one-dimensional) and compound 6 (three-dimensional). In only two cases [compounds 1 and 4], are weak cation-anion or cation-cation π-π interactions found while weak aromatic C-H…O interactions are insignificant. The study shows that all compounds fit the previously formulated classification scheme for primary and secondary interactive modes for proton-transfer compounds of 3,5-dinitrosalicylic acid but there are some unusual variants.

Ethane-1,2-diaminium 4,4'-sulfonyldibenzoate

In the title compound 2(C2H10N2+) C14H8O6S2-, both the ethylenediaminium cations and the 4,4'-sulfonyldibenzoate dianions have crystallographic two-fold rotational symmetry and are interlinked by aminium N-H...O(carboxyl) hydrogen-bonding associations giving sheets which extend along (101) and are further linked down b forming a three-dimensional structure.

Emergency health services : demand and service delivery models. Monograph 1: literature review and activity trends

Emergency Health Services (EHS), encompassing hospital-based Emergency Departments (ED) and pre-hospital ambulance services, are a significant and high profile component of Australia’s health care system and congestion of these, evidenced by physical overcrowding and prolonged waiting times, is causing considerable community and professional concern. This concern relates not only to Australia’s capacity to manage daily health emergencies but also the ability to respond to major incidents and disasters. EHS congestion is a result of the combined effects of increased demand for emergency care, increased complexity of acute health care, and blocked access to ongoing care (e.g. inpatient beds). Despite this conceptual understanding there is a lack of robust evidence to explain the factors driving increased demand, or how demand contributes to congestion, and therefore public policy responses have relied upon limited or unsound information. The Emergency Health Services Queensland (EHSQ) research program proposes to determine the factors influencing the growing demand for emergency health care and to establish options for alternative service provision that may safely meet patient’s needs. The EHSQ study is funded by the Australian Research Council (ARC) through its Linkage Program and is supported financially by the Queensland Ambulance Service (QAS). This monograph is part of a suite of publications based on the research findings that examines the existing literature, and current operational context. Literature was sourced using standard search approaches and a range of databases as well as a selection of articles cited in the reviewed literature. Public sources including the Australian Institute of Health and Welfare (AIHW), the Council of Ambulance Authorities (CAA) Annual Reports, Australian Bureau of Statistics (ABS) and Department of Health and Ageing (DoHA) were examined for trend data across Australia.

Intention, foresight and ending life : a response to "The Double Effect effect" by Charles Foster, Jonathan Herring, Karen Melham and Tony Hope, (CQ 20(1))

In this paper I examine the recent arguments by Charles Foster, Jonathan Herring, Karen Melham and Tony Hope against the utility of the doctrine of double effect. One basis on which they reject the utility of the doctrine is their claim that it is notoriously difficult to apply what they identify as its 'core' component, namely, the distinction between intention and foresight. It is this contention that is the primarily focus of my article. I argue against this claim that the intention/foresight distinction remains a fundamental part of the law in those jurisdictions where intention remains an element of the offence of murder and that, accordingly, it is essential ro resolve the putative difficulties of applying the intention/foresight distinction so as to ensure the integrity of the law of murder. I argue that the main reasons advanced for the claim that the intention/foresight distinction is difficult to apply are ultimately unsustainable, and that the distinction is not as difficult to apply as the authors suggest.