Effect of l -Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role

Behav Pharmacol. 2023 Aug 1;34(5):263-274. doi: 10.1097/FBP.0000000000000733. Epub 2023 Jun 24.

Abstract

Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l -Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l -Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l -Dopa/benserazide administration in six groups (control, l -Dopa 25 mg/kg, l -Dopa 75 mg/kg, temozolomide, temozolomide + l -Dopa 25 mg/kg, and temozolomide + l -Dopa 75 mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomide + l -Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l -Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l -Dopa antineuroinflammatory effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Cognitive Dysfunction* / chemically induced
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / metabolism
  • Hippocampus
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism
  • Mice
  • RNA, Messenger / metabolism
  • Temozolomide / metabolism
  • Temozolomide / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Temozolomide
  • Brain-Derived Neurotrophic Factor
  • Tumor Necrosis Factor-alpha
  • RNA, Messenger