scholarly journals Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin‐1 receptor antagonist in rats

2018 ◽  
Vol 50 (3) ◽  
pp. 2602-2612 ◽  
Author(s):  
Morgan H. James ◽  
Hannah E. Bowrey ◽  
Colin M. Stopper ◽  
Gary Aston‐Jones
Keyword(s):  
Receptor Antagonist ◽  
Therapeutic Efficacy ◽  
Demand Elasticity ◽  
Hypocretin 1

scholarly journals Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin/hypocretin-1 receptor antagonist in rats

2018 ◽  
Author(s):  
Morgan H James ◽  
Hannah E Bowrey ◽  
Colin M Stopper ◽  
Gary Aston-Jones
Keyword(s):  
Behavioral Economics ◽  
Receptor Antagonist ◽  
Demand Elasticity ◽  
Self Administration ◽  
High Demand ◽  
Drug Experience ◽  
Drug Seeking ◽  
Translational Approach ◽  
Administration Schedules ◽  
Hypocretin 1

AbstractBehavioral economics is a powerful, translational approach for measuring drug demand in both humans and animals. Here, we asked if demand for cocaine in rats with limited drug experience could be used to identify individuals most at risk of expressing an addiction phenotype following either long (LgA) or intermittent (IntA) access self-administration schedules, both of which model the transition to uncontrolled drug seeking. Moreover, because the orexin-1 receptor antagonist SB-334867 (SB) is particularly effective at reducing drug-seeking in highly motivated individuals, we asked whether demand measured after prolonged drug experience could predict SB efficacy. Demand elasticity (α) measured immediately following acquisition of cocaine self-administration (‘baseline α’) was positively correlated with α assessed after 2w of LgA or IntA. Baseline α also predicted the magnitude of compulsive responding for cocaine, drug seeking in initial abstinence, and cued reinstatement following LgA, IntA or standard short access (ShA). When demand was measured after LgA, IntA or ShA, α predicted the same addiction endophenotypes predicted by baseline α, as well as primed reinstatement and the emergence of negative emotional mood behavior following abstinence. Post-LgA/IntA/ShA α also predicted the efficacy of SB, such that high demand rats showed greater reductions in motivation for cocaine following SB (10 and 30mg/kg) compared to low demand rats. Together, these findings indicate that α might serve as a behavioral biomarker to predict individuals most likely to progress from controlled to uncontrolled drug use, and to identify individuals most likely to benefit from orexin-based therapies for the treatment of addiction.

scholarly journals The Therapeutic Efficacy of VP-343, a Selective Vasopressin V2 Receptor Antagonist, in the Experimental SIADH Rat Model.

2000 ◽  
Vol 23 (11) ◽  
pp. 1323-1327 ◽  
Author(s):  
Akira NAITO ◽  
Hisashi HASEGAWA ◽  
Takashi KURASAWA ◽  
Yasuhiro OHTAKE ◽  
Hidehiko MATSUKAWA ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Rat Model ◽  
Therapeutic Efficacy ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor ◽  
Vasopressin V2 Receptor Antagonist ◽  
V2 Receptor Antagonist

scholarly journals The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice

2016 ◽  
Vol 1636 ◽  
pp. 74-80 ◽  
Author(s):  
Marcelo F. Lopez ◽  
David E. Moorman ◽  
Gary Aston-Jones ◽  
Howard C. Becker
Keyword(s):  
Receptor Antagonist ◽  
Ethanol Drinking ◽  
Hypocretin 1

Therapeutic efficacy of a novel LPA1 receptor antagonist, UD-009, in a bleomycin-induced pulmonary fibrosis model

2016 ◽  
Author(s):  
Kenji Nishikawa ◽  
Eiji Okanari ◽  
Yuuko Shinohara ◽  
Hironobu Matsunaga ◽  
Hiroshi Nishida ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Receptor Antagonist ◽  
Therapeutic Efficacy ◽  
Lpa1 Receptor

The interaction of histamine with other bronchoconstrictor mediators

1987 ◽  
Vol 65 (3) ◽  
pp. 442-447 ◽  
Author(s):  
J. F. Burka
Keyword(s):  
Arachidonic Acid ◽  
Receptor Antagonist ◽  
Therapeutic Efficacy ◽  
Platelet Activating Factor ◽  
Airway Hyperreactivity ◽  
Specific Receptor ◽  
Arachidonic Acid Metabolites ◽  
Other Substances ◽  
Acid Metabolites ◽  
Antihistaminic Drugs

The lack of therapeutic efficacy of antihistaminic drugs in the treatment of asthma has led to the search and discovery of other bronchoconstrictor agents, particularly leukotrienes, thromboxanes, and platelet-activating factor. However, specific receptor antagonist for any of these substances have also not been particularly effective in inhibiting allergic bronchoconstriction. It is now generally accepted that histamine, arachidonic acid metabolites, platelet-activating factor, and possibly other substances are all involved to varying degrees in asthma and may indeed interact. This paper reviews the interaction of these mediators and how they contribute to airway hyperreactivity.

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