Addictive drugs modify neurogenesis, synaptogenesis and synaptic plasticity to impair memory formation through neurotransmitter imbalances and signaling dysfunction

Neurochem Int. 2023 Oct:169:105572. doi: 10.1016/j.neuint.2023.105572. Epub 2023 Jul 7.

Abstract

Drug abuse changes neurophysiological functions at multiple cellular and molecular levels in the addicted brain. Well-supported scientific evidence suggests that drugs negatively affect memory formation, decision-making and inhibition, and emotional and cognitive behaviors. The mesocorticolimbic brain regions are involved in reward-related learning and habitual drug-seeking/taking behaviors to develop physiological and psychological dependence on the drugs. This review highlights the importance of specific drug-induced chemical imbalances resulting in memory impairment through various neurotransmitter receptor-mediated signaling pathways. The mesocorticolimbic modifications in the expression levels of brain-derived neurotrophic factor (BDNF) and the cAMP-response element binding protein (CREB) impair reward-related memory formation following drug abuse. The contributions of protein kinases and microRNAs (miRNAs), along with the transcriptional and epigenetic regulation have also been considered in memory impairment underlying drug addiction. Overall, we integrate the research on various types of drug-induced memory impairment in distinguished brain regions and provide a comprehensive review with clinical implications addressing the upcoming studies.

Keywords: Cognitive dysfunction; Drug abuse; Memory impairment; Neurotransmitters; Signaling pathways.

Publication types

  • Review

MeSH terms

  • Brain-Derived Neurotrophic Factor / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Epigenesis, Genetic*
  • Hippocampus / metabolism
  • Humans
  • Memory Disorders / chemically induced
  • Memory Disorders / metabolism
  • Neurogenesis
  • Neuronal Plasticity / physiology
  • Signal Transduction / physiology
  • Substance-Related Disorders* / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein