Modafinil reduces amphetamine preference and prevents anxiety-like symptoms during drug withdrawal in young rats: Involvement of dopaminergic targets in VTA and striatum

Drug abuse and addiction are overwhelming health problems mainly during adolescence. Based on a previous study of our research group, the rats that received modafinil (MD) during the adolescence showed less preference for amphetamine (AMPH) in adulthood. Our current hypothesis is that MD will show b...

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Bibliographic Details
Published in:Progress in neuro-psychopharmacology & biological psychiatry 2019-06, Vol.92, p.199-206
Main Authors: Dias, Verônica Tironi, Rosa, Higor Zuquetto, D'avila, Lívia Ferraz, Vey, Luciana Taschetto, Barcelos, Raquel Cristine Silva, Burger, Marilise Escobar
Format: Article
Language:English
Subjects:
D1 receptor
D2 receptor
Dopamine transporter
Reward
Tyrosine hydroxylase
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Summary:Drug abuse and addiction are overwhelming health problems mainly during adolescence. Based on a previous study of our research group, the rats that received modafinil (MD) during the adolescence showed less preference for amphetamine (AMPH) in adulthood. Our current hypothesis is that MD will show beneficial effects against AMPH preference and abstinence symptoms during adolescence, a critical lifetime period when drug hedonic effects are more pronounced. We investigated the influence of MD pretreatment on AMPH preference in conditioned place preference (CPP) paradigm in adolescent rats and anxiety-like symptoms during drug withdrawal (48 h after the last AMPH dose) in elevated plus maze (EPM) task. Besides that, oxidative and molecular status were evaluated in the ventral tegmental area (VTA) and striatum. Our findings showed, as it was expected, that adolescent animals developed AMPH preference together with anxiety-like symptoms during the drug withdrawal while the MD pretreatment prevented those behaviors. Besides promoting benefits on reward parameters, MD was able to preserve VTA and striatum from oxidative damages. This was observed by the increased catalase activity and reduced generation of reactive species and lipid peroxidation, which were inversely modified by AMPH exposure. At molecular level, MD exerted an interesting modulatory activity on the VTA and induced an up-regulation in striatal dopaminergic targets (TH, DAT, D1R and D2R). So far, during the adolescence, MD presented beneficial behavioral outcomes that could be attributed to its modulatory activity on the striatal dopaminergic system in an attempt to maintain the adequate dopamine levels. [Display omitted] •Modafinil (MD) pretreatment decreased AMPH-induced CPP in adolescent rats.•MD decreased anxiety in adolescent rats after 48 h of AMPH withdrawal.•MD pretreatment improved oxidative status of VTA and striatum after AMPH exposure.•MD pretreatment induced an up-regulation of dopaminergic targets in the striatum.
ISSN:0278-5846
1878-4216
DOI:10.1016/j.pnpbp.2019.01.007