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Effects of the monoamine stabilizer, (-)-OSU6162, on cocaine-induced locomotion and conditioned place preference in mice

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Abstract

Cocaine addiction is a severe mental disorder for which few treatment options are available. The underlying mechanisms include facilitation of monoamine-neurotransmission, particularly dopamine. Here, we tested the hypothesis that the monoamine stabilizers, (-)-OSU6162 ((3S)-3-(3-methylsulfonylphenyl)-1-propylpiperidine) and aripiprazole (7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one), prevent cocaine-induced behaviors. Male Swiss mice received injections of (-)-OSU6162 or aripiprazole and cocaine and were tested for cocaine-induced hyperlocomotion, locomotor sensitization, and acquisition and expression of conditioned place preference (CPP). The increase in the distance traveled induced by cocaine (20 mg/kg) was prevented by pretreatment with aripiprazole (1 and 10 mg/kg), whereas (-)-OSU6162 (3 mg/kg) exerted a minor effect. Aripiprazole, however, also impaired spontaneous locomotion. Neither (-)-OSU6162 nor aripiprazole interfered with the locomotor sensitization and expression of CPP induced by cocaine (15 mg/kg). (-)-OSU6162 (3 mg/kg), but not aripiprazole, prevented the acquisition of CPP induced by cocaine (15 mg/kg). (-)-OSU6162 exerts a minor effect in reducing cocaine-induced stimulatory activity and context-related memories, which are responsible for triggering drug seeking. Further studies are required to establish whether (-)-OSU6162 could be a candidate drug for the treatment of cocaine addiction.

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Funding

The authors disclose the following financial supports for the research, authorship, and/or publication of this article: This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq [grant number 406122/2016-4]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES [grant number 88882.315961/2019-01]; and Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP [grant number 2017/24304-0].

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  1. Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Pres. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil

    Laila Asth, Lia P. Iglesias, Rayssa C. Briânis, Anna P. Marçal, Nícia P. Soares, Daniele C. Aguiar & Fabrício A. Moreira

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  1. Laila Asth
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Contributions

LA and FAM conceived and designed research. LA, LIP, RBC, APM, and NPS conducted experiments. LA, LIP, and DCA analyzed data. LA, DCA, and FAM wrote the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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All experimental procedures adopted for in vivo studies were in accordance with the Brazilian Society of Neuroscience and Behavior Guidelines for the Care and Use of Laboratory Animals and were approved by the local ethics committee (CEUA–UFMG) under the protocol 78/2014.

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Asth, L., Iglesias, L.P., Briânis, R.C. et al. Effects of the monoamine stabilizer, (-)-OSU6162, on cocaine-induced locomotion and conditioned place preference in mice. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1143–1152 (2021). https://doi.org/10.1007/s00210-021-02053-x

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