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Assessment of a glycine uptake inhibitor in animal models of effort-related choice behavior: implications for motivational dysfunctions

Content Provider	Springer Nature Link
Author	Yohn, Samantha E. Alberati, Daniela Correa, Merce Salamone, John D.
Copyright Year	2017
Abstract	Motivated behavior can be characterized by a substantial exertion of effort, and organisms often make effort-related decisions based upon analyses of work-related response costs and reinforcement preference. Moreover, alterations in effort-based choice can be seen in people with major depression and schizophrenia. Effort-related decision making is studied using tasks offering choices between high effort options leading to highly valued reinforces vs low effort/low reward options. Interference with dopamine (DA) transmission by administration of the DA D2 family antagonist haloperidol biases behavior towards the lower effort option that can be obtained with minimal work, and previous research has shown that DA interacts with other transmitters, including adenosine and GABA, to regulate effort-based choice.The present studies focused upon the ability of the glycine transport inhibitor bitopertin to attenuate haloperidol-induced shifts in effort-related choice behavior.Effort-based choice in rats was assessed using the concurrent fixed ratio (FR) 5/chow feeding choice task and the T-maze barrier choice procedure.Haloperidol shifted effort-based choice, biasing animals towards the low effort option in each task. Co-administration of bitopertin (1.0–10.0 mg/kg) significantly attenuated haloperidol-induced shifts in choice behavior, but the same doses of bitopertin had no effect when administered alone.These results indicated that elevation of extracellular glycine via inhibition of glycine uptake was able to reverse the effects of D2 antagonism. Increases in extracellular glycine, possibly through actions on the glycine allosteric site on the NMDA receptor, may be a useful strategy for treating motivational dysfunctions in humans.
Starting Page	1525
Ending Page	1534
Page Count	10
File Format	PDF
ISSN	00333158
Journal	Psychopharmacology
Volume Number	234
Issue Number	9-10
e-ISSN	14322072
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-01-12
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Dopamine Motivation Fatigue Anergia Glycine uptake NMDA Neurosciences Pharmacology/Toxicology Psychiatry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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