GABA(A) receptor positive allosteric modulators modify the abuse-related behavioral and neurochemical effects of methamphetamine, in rhesus monkeys

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dc.contributor.author Berro, Lais F. [UNIFESP]
dc.contributor.author Andersen, Monica L. [UNIFESP]
dc.contributor.author Tufik, Sergio [UNIFESP]
dc.contributor.author Howell, Leonard L.
dc.date.accessioned 2019-08-19T11:49:38Z
dc.date.available 2019-08-19T11:49:38Z
dc.date.issued 2017
dc.identifier http://dx.doi.org/10.1016/j.neuropharm.2017.05.010
dc.identifier.citation Neuropharmacology. Oxford, v. 123, p. 299-309, 2017.
dc.identifier.issn 0028-3908
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/51362
dc.description.abstract GABA(A) receptor positive allosteric modulators (GABA(A) receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABA(A) receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABA(A) receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general daytime activity were evaluated with Actiwatch monitors. Methamphetamine self-administration (0.03 mg/kg/inf) was evaluated during morning sessions. Methamphetamine-induced dopamine overflow was assessed through in vivo microdialysis targeting the nucleus accumbens. Nighttime treatment with either temazepam or eszopiclone was ineffective in improving sleep-like measures disrupted by methamphetamine self-administration. Acute pretreatment with a low dose of temazepam before self-administration sessions increased methamphetamine self administration without affecting normal daytime home-cage activity. At a high dose, acute temazepam pretreatment decreased methamphetamine self-administration and attenuated methamphetamine-induced increases in dopamine in the nucleus accumbens, without decreasing general daytime activity. Acute eszopiclone treatment exerted no effects on methamphetamine intake or drug-induced increases in dopamine. Our study suggests that treatments based on GABA(A) receptor modulators are not effective for the treatment of sleep disruption in the context of psychostimulant use. In addition, distinct GABA(A) receptor modulators differentially modulated the abuse-related effects of methamphetamine, with acute treatment with the high efficacy GABA(A) receptor modulator temazepam decreasing the behavioral and neurochemical effects of methamphetamine. (C) 2017 Elsevier Ltd. All rights reserved. en
dc.description.sponsorship USPHS
dc.description.sponsorship AFIP
dc.description.sponsorship FAPESP
dc.format.extent 299-309
dc.language.iso eng
dc.publisher Pergamon-Elsevier Science Ltd
dc.rights Acesso restrito
dc.subject Methamphetamine en
dc.subject Temazepam en
dc.subject Eszopiclone en
dc.subject Self-administration en
dc.subject Sleep en
dc.subject Microdialysis en
dc.subject Nonhuman primates en
dc.title GABA(A) receptor positive allosteric modulators modify the abuse-related behavioral and neurochemical effects of methamphetamine, in rhesus monkeys en
dc.type Artigo
dc.description.affiliation Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USA
dc.description.affiliation Univ Fed São Paulo, Dept Psychobiol, R Napolao Barros 925, BR-04021002 São Paulo, SP, Brazil
dc.description.affiliation Emory Univ, Sch Med, Dept Psychiat & Behav Sci, 954 Gatewood Rd NE, Atlanta, GA 30329 USA
dc.description.affiliationUnifesp Univ Fed São Paulo, Dept Psychobiol, R Napolao Barros 925, BR-04021002 São Paulo, SP, Brazil
dc.description.sponsorshipID USPHS: DA10344
dc.description.sponsorshipID USPHS: DA031246
dc.description.sponsorshipID USPHS: ODP51OD11132
dc.description.sponsorshipID FAPESP: 2015/25482-3
dc.identifier.doi 10.1016/j.neuropharm.2017.05.010
dc.description.source Web of Science
dc.identifier.wos WOS:000406987300027



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