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

Naunyn Schmiedebergs Arch Pharmacol. 2021 Jun;394(6):1143-1152. doi: 10.1007/s00210-021-02053-x. Epub 2021 Jan 20.

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.

Keywords: (-)-OSU-6162; Aripiprazole; Cocaine; Conditioned place preference; Hyperlocomotion; Locomotor sensitization.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aripiprazole / administration & dosage
  • Aripiprazole / pharmacology*
  • Behavior, Animal / drug effects
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Conditioning, Psychological / drug effects
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior / drug effects
  • Locomotion / drug effects*
  • Male
  • Mice
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*

Substances

  • Piperidines
  • OSU 6162
  • Aripiprazole
  • Cocaine