Resveratrol by elevating the SIRT1 BDNF, GDNF and PSD95 levels reduce heroin addiction related behaviors

Neurosci Lett. 2024 Oct 15:841:137934. doi: 10.1016/j.neulet.2024.137934. Epub 2024 Aug 13.

Abstract

Objective: To study the effects of resveratrol on heroin addiction-related behaviors and to preliminarily explore the possible intervention mechanism of resveratrol in heroin dependence.

Methods: The effects of resveratrol on heroin withdrawal symptoms were observed by naloxone; The effect of resveratrol on heroin reward memory acquisition was detected by CPP paradigm; The effect of resveratrol on the mental excitability of heroin was tested by open field experiment; The effect of resveratrol on heroin spatial learning and memory was tested by water maze test. Western blot was used to detect Sirtuin 1 (SIRT1) Expression of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), and postsynaptic density protein (PSD95).

Results: The behavioral results showed that the withdrawal behavior of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05), and the shift score of the conditioned place preference test of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05) The spatial learning and memory ability of the water maze in the resveratrol intervention group was improved compared with the heroin chronic dependence group (P<0.05), and the mental excitability of the resveratrol intervention group was lower than that of the heroin chronic dependence group (P<0.05), but higher than that of the saline group (P<0.05); SIRT1 The expression levels of BDNF, GDNF and PSD95 protein were significantly increased (P<0.05).

Conclusion: The behavioral results of this study suggest that resveratrol can be used as a potential drug to treat heroin dependence. At the same time, SIRT1 The expression of BDNF, GDNF, and PSD95 increased; SIRT1, BDNF, GDNF, and PSD95 play an essential role in heroin addiction.

Keywords: Addiction-related behaviors; BDNF; Heroin; NAc; Resveratrol; SIRT1.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor* / drug effects
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Disks Large Homolog 4 Protein* / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor* / metabolism
  • Heroin Dependence* / drug therapy
  • Heroin Dependence* / metabolism
  • Heroin Dependence* / psychology
  • Male
  • Maze Learning / drug effects
  • Resveratrol* / administration & dosage
  • Resveratrol* / pharmacology
  • Sirtuin 1* / metabolism
  • Substance Withdrawal Syndrome / drug therapy
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / psychology

Substances

  • Brain-Derived Neurotrophic Factor
  • Sirtuin 1
  • Disks Large Homolog 4 Protein
  • Glial Cell Line-Derived Neurotrophic Factor
  • Resveratrol