The effect of paeoniflorin on the rewarding effect of methamphetamine and the associated cognitive impairment in mice

Metab Brain Dis. 2024 Nov 20;40(1):27. doi: 10.1007/s11011-024-01462-0.

Abstract

Chronic exposure to methamphetamine (METH) has been suggested to cause METH use disorder and severe cognitive impairment. Paeoniflorin (PF) is a monoterpenoid glycoside with various beneficial effects, including anti-inflammatory, antioxidant and antidepressant. The current study was designed to investigate the effect of PF (30 mg/kg, i.p.) on the rewarding effect of METH (2.5 mg/kg, i.p.) and the associated cognitive impairment, using the animal model of conditioned place preference, new location reorganization test, new object reorganization test and Y-maze test. METH induced conditioned place preference, accompanied by increased expression of synapse-associated proteins in the ventral target areas (VTA) and nucleus accumbens (NAc). In addition, METH induced significant cognitive impairment and decreased the expression of synapse-associated proteins in the hippocampus (Hip). Administration of PF decreased the rewarding effect of METH and the expression of synapse-associated proteins in the VTA or NAc. PF was also effective to improve METH-induced cognitive impairment by upregulating the expression of synapse-associated proteins in the Hip. Therefore, PF could be a potential agent for the treatment of METH use disorder and the associated cognitive impairment.

Keywords: Methamphetamine; Paeoniflorin; Rewarding effect; Synaptic protein; VTA.

MeSH terms

  • Animals
  • Central Nervous System Stimulants / pharmacology
  • Central Nervous System Stimulants / toxicity
  • Cognitive Dysfunction* / chemically induced
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / metabolism
  • Glucosides* / pharmacology
  • Glucosides* / therapeutic use
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Maze Learning / drug effects
  • Methamphetamine* / toxicity
  • Mice
  • Monoterpenes* / pharmacology
  • Monoterpenes* / therapeutic use
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Reward*
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism

Substances

  • Methamphetamine
  • Glucosides
  • peoniflorin
  • Monoterpenes
  • Central Nervous System Stimulants