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

• Published in: Behavioural pharmacology Vol. 34; no. 5; p. 263
• Main Authors: Salarinejad, Alireza, Esmaeilpour, Khadije, Shabani, Mohammad, Jafarinejad-Farsangi, Saeideh, Pardakhty, Abbas, Asadi-Shekaari, Majid, Ahmadi-Zeidabadi, Meysam
• Format: Journal Article
• Language: English
• Published: England 01.08.2023
• Subjects: 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
• DOI: 10.1097/FBP.0000000000000733

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.