Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/111556
Title: Behavioral and Dopamine Transporter Binding Properties of the Modafinil Analog (S, S)-CE-158: Reversal of the Motivational Effects of Tetrabenazine and Enhancement of Progressive Ratio Responding
Authors: Rotolo, R. A.
Kalaba, P.
Dragacevic, V.
Presby, R. E.
Neri, J.
Robertson, E.
Yang, J. -H.
Correa, M.
Bakulev, V.
Volkova, N. N.
Pifl, C.
Lubec, G.
Salamone, J. D.
Issue Date: 2020
Publisher: Springer Science and Business Media Deutschland GmbH
Springer Science and Business Media LLC
Citation: Behavioral and Dopamine Transporter Binding Properties of the Modafinil Analog (S, S)-CE-158: Reversal of the Motivational Effects of Tetrabenazine and Enhancement of Progressive Ratio Responding / R. A. Rotolo, P. Kalaba, V. Dragacevic et al. // Psychopharmacology. — 2020. — Vol. 237. — Iss. 11. — P. 3459-3470.
Abstract: Rationale: Atypical dopamine (DA) transport blockers such as modafinil and its analogs may be useful for treating motivational symptoms of depression and other disorders. Previous research has shown that the DA depleting agent tetrabenazine can reliably induce motivational deficits in rats, as evidenced by a shift towards a low-effort bias in effort-based choice tasks. This is consistent with human studies showing that people with major depression show a bias towards low-effort activities. Objectives: Recent studies demonstrated that the atypical DA transport (DAT) inhibitor (S)-CE-123 reversed tetrabenazine-induced motivational deficits, increased progressive ratio (PROG) lever pressing, and increased extracellular DA in the nucleus accumbens. In the present studies, a recently synthesized modafinil analog, (S, S)-CE-158, was assessed in a series of neurochemical and behavioral studies in rats. Results: (S, S)-CE-158 demonstrated the ability to reverse the effort-related effects of tetrabenazine and increase selection of high-effort PROG lever pressing in rats tested on PROG/chow feeding choice task. (S, S)-CE-158 showed a high selectivity for inhibiting DAT compared with other monoamine transporters, and systemic administration of (S, S)-CE-158 increased extracellular DA in the nucleus accumbens during the behaviorally active time course, which is consistent with the effects of (S)-CE-123 and other DAT inhibitors that enhance high-effort responding. Conclusions: These studies provide an initial neurochemical characterization of a novel atypical DAT inhibitor, and demonstrate that this compound is active in models of effort-related choice. This research could contribute to the development of novel compounds for the treatment of motivational dysfunctions in humans. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Keywords: ANERGIA
DEPRESSION
DOPAMINE
FATIGUE
MODAFINIL
MOTIVATION
SYNTHESIS
TRANSPORT
5 [[[(3 BROMOPHENYL)(PHENYL)METHYL]SULFINYL]METHYL]THIAZOLE
ANTIDEPRESSANT AGENT
CE 158
DOPAMINE TRANSPORTER
TETRABENAZINE
UNCLASSIFIED DRUG
ADRENERGIC RECEPTOR AFFECTING AGENT
DOPAMINE TRANSPORTER
MODAFINIL
PROTEIN BINDING
TETRABENAZINE
ADULT
ANIMAL EXPERIMENT
ANIMAL TISSUE
ANTIDEPRESSANT ACTIVITY
ARTICLE
CAUDATE NUCLEUS
CONTROLLED STUDY
DECISION MAKING
DOPAMINERGIC TRANSMISSION
DRUG DETERMINATION
DRUG EFFECT
DRUG POTENCY
DRUG PROTEIN BINDING
DRUG STRUCTURE
FEEDING
IC50
IN VITRO STUDY
MALE
MOTIVATION
NEUROCHEMISTRY
NONHUMAN
NUCLEUS ACCUMBENS
PRIORITY JOURNAL
PROTEIN EXPRESSION
PUTAMEN
RAT
SCANNING ELECTRON MICROSCOPY
SYSTEMIC THERAPY
ANIMAL
DOSE RESPONSE
FEEDING BEHAVIOR
HEK293 CELL LINE
HUMAN
METABOLISM
PHYSIOLOGY
SPRAGUE DAWLEY RAT
ADRENERGIC UPTAKE INHIBITORS
ANIMALS
CHOICE BEHAVIOR
DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS
DOSE-RESPONSE RELATIONSHIP, DRUG
FEEDING BEHAVIOR
HEK293 CELLS
HUMANS
MALE
MODAFINIL
NUCLEUS ACCUMBENS
PROTEIN BINDING
RATS
RATS, SPRAGUE-DAWLEY
TETRABENAZINE
URI: http://hdl.handle.net/10995/111556
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85089100938
PURE ID: 14163499
ISSN: 0033-3158
metadata.dc.description.sponsorship: The authors would like to acknowledge Eurofins DiscoverX Corporation (Fremont, CA).
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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