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

Author(s)

Asth, Laila ^[1] ; Iglesias, Lia P. ^[1] ; Brianis, Rayssa C. ^[1] ; Marcal, Anna P. ^[1] ; Soares, Nicia P. ^[1] ; Aguiar, Daniele C. ^[1] ; Moreira, Fabricio A. ^[1]

Affiliation

^[1] Univ Fed Minas Gerais, Inst Biol Sci, Dept Pharmacol, Av Pres Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 394, n. 6 JAN 2021.
• Web of Science Citations: 0

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-q uinolin-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. (AU)

• FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants