Assessment of a glycine uptake inhibitor in animal models of effort-related choice behavior: implications for motivational dysfunctions
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Other documents of the author: Yohn, Samantha E.; Alberati, Daniela; Correa, Merce; Salamone, John
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Title
Assessment of a glycine uptake inhibitor in animal models of effort-related choice behavior: implications for motivational dysfunctionsDate
2017Publisher
Springer VerlagISSN
0033-3158; 1432-2072Bibliographic citation
Yohn, S.E., Alberati, D., Correa, M. et al. Psychopharmacology (2017) 234: 1525. doi:10.1007/s00213-016-4523-3Type
info:eu-repo/semantics/articlePublisher version
https://link.springer.com/article/10.1007/s00213-016-4523-3Version
info:eu-repo/semantics/publishedVersionSubject
Abstract
Rationale Motivated behavior can be characterized by a substantial
exertion of effort, and organisms often make effortrelated
decisions based upon analyses of work-related response
costs and reinforcement preference. ... [+]
Rationale Motivated behavior can be characterized by a substantial
exertion of effort, and organisms often make effortrelated
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.
Objectives The present studies focused upon the ability of the
glycine transport inhibitor bitopertin to attenuate haloperidolinduced
shifts in effort-related choice behavior.
Methods 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.
Results Haloperidol shifted effort-based choice, biasing animals
towards the low effort option in each task. Coadministration
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.
Conclusions 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. [-]
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Psychopharmacology (2017) 234Rights
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