4.6 Article

Selegiline ameliorates depression-like behaviors in rodents and modulates hippocampal dopaminergic transmission and synaptic plasticity

Journal

BEHAVIOURAL BRAIN RESEARCH
Volume 359, Issue -, Pages 353-361

Publisher

ELSEVIER
DOI: 10.1016/j.bbr.2018.10.032

Keywords

Selegiline; Monoamine oxidase inhibitor; Depression; Hippocampus; Synaptic plasticity; Long-term potentiation

Ask authors/readers for more resources

Selegiline, an irreversible inhibitor of monoamine oxidase (MAO)-type B, is widely prescribed for Parkinson's disease and, at higher doses, for major and atypical depression, whereby it is non-selectively inhibitory to both MAO-A and MAO-B activities. MAO inhibitors have been considered to function as antidepressants through MAO-A inhibition. We have previously reported that selegiline exerts antidepressant-like effects in the mouse forced swim test (FST) via dopamine Dl receptor activation. Our objective was to elucidate the mechanisms underlying the antidepressant-like effects of selegiline. We also tested another propargylamine MAO-B inhibitor, rasagiline. Triple subcutaneous injection (at 24, 5, and 1 h prior to behavioral testing) with selegiline (10 mg/kg/ injection), but not rasagiline (1, 3, or 10 mg/kg/injection), reduced the immobility time in the mouse FST and rat tail suspension test. In the hippocampus and prefrontal cortex of mice subjected to the FST, selegiline and rasagiline completely inhibited MAO-B activities. However, selegiline suppressed MAO-A activities and monoamine turnover rates at a lesser degree than rasagiline at the same doses, indicating that the antidepressant-like effects of selegiline are independent of MAO-A inhibition. Moreover, selegiline, but not rasagiline, increased the hippocampal dopamine content. A single subcutaneous administration of 10 mg/kg selegiline, but not of rasagiline, significantly prevented hippocampal CA1 long-term potentiation impairment, induced by low-frequency stimulation prior to high-frequency stimulation in rats. These results suggest that the antidepressant-like effects of selegiline are attributable to enhancement of dopaminergic transmission and prevention of the impairment of synaptic plasticity in the hippocampus.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Clinical Neurology

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles

Tetsuya Nishimura, Kazue Takahata, Yuri Kosugi, Takaaki Tanabe, Shizuko Muraoka

JOURNAL OF NEURAL TRANSMISSION (2017)

Article Behavioral Sciences

Selegiline increases on time without exacerbation of dyskinesia in 6-hydroxydopamine-lesioned rats displaying L-Dopa-induced wearing-off and abnormal involuntary movements

Hiroko Tsunekawa, Kazue Takahata, Motoki Okano, Toshiko Ishikawa, Hiroshi Satoyoshi, Tetsuya Nishimura, Naoya Hoshino, Shizuko Muraoka

BEHAVIOURAL BRAIN RESEARCH (2018)

Article Neurosciences

Myocardial nerve fibers are preserved in MPTP-treated mice, despite cardiac sympathetic dysfunction

Takeshi Amino, Toshiki Uchihara, Hiroko Tsunekawa, Kazue Takahata, Seiichiro Shimazu, Hidehiro Nlizusawa, Satoshi Orimo

NEUROSCIENCE RESEARCH (2008)

Article Behavioral Sciences

Selegiline Recovers Synaptic Plasticity in the Medial Prefrontal Cortex and Improves Corresponding Depression-Like Behavior in a Mouse Model of Parkinson's Disease

Motoki Okano, Kazue Takahata, Junya Sugimoto, Shizuko Muraoka

FRONTIERS IN BEHAVIORAL NEUROSCIENCE (2019)

Article Pharmacology & Pharmacy

Fabry disease-associated globotriaosylceramide induces mechanical allodynia via activation of signaling through proNGF-p75NTR but not mature NGF-TrkA

Junya Sugimoto, Hiroshi Satoyoshi, Kazue Takahata, Shizuko Muraoka

Summary: Fabry disease is an X-linked metabolic storage disorder caused by lysosomal alpha-galactosidase A deficiency. Research suggests that the nerve growth factor signaling pathway may be a potential cause of Fabry disease-associated pain.

EUROPEAN JOURNAL OF PHARMACOLOGY (2021)

Article Neurosciences

Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion In Vitro and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease

Yoshitsugu Nakamura, Shigeki Arawaka, Hiroyasu Sato, Asuka Sasaki, Taro Shigekiyo, Kazue Takahata, Hiroko Tsunekawa, Takeo Kato

Summary: Inhibiting MAO-B enzymatic activity can facilitate the secretion of alpha-synuclein and delay protein aggregation and loss of dopaminergic neurons in Parkinson's disease models.

JOURNAL OF NEUROSCIENCE (2021)

Article Clinical Neurology

Effects of selegiline on antioxidant systems in the nigrostriatum in rat

K Takahata, S Shimazu, H Katsuki, F Yoneda, A Akaike

JOURNAL OF NEURAL TRANSMISSION (2006)

Article Pharmacology & Pharmacy

Effects of selegiline, alone or with donepezil on memory impairment in rats

K Takahata, A Minami, H Kusumoto, S Shimazu, F Yoneda

EUROPEAN JOURNAL OF PHARMACOLOGY (2005)

Article Pharmacology & Pharmacy

Effects of R-(-)-BPAP on the expressions of neurotrophins and their receptors in mesencephalic slices

C Hirami, K Takahata, S Shimazu, F Yoneda, K Hayashi, H Katsuki, A Akaike

BIOLOGICAL & PHARMACEUTICAL BULLETIN (2005)

Article Clinical Neurology

Effects of monoamine oxidase inhibitors on the diethyldithiocarbamate-induced enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in C57BL/6 mice

K Takahata, S Shimazu, F Yoneda, M Ogawa, Y Iida, H Saji

JOURNAL OF NEURAL TRANSMISSION (2003)

Article Pharmacology & Pharmacy

Retinal neurotoxicity of nitric oxide donors with different half-life of nitric oxide release:: Involvement of N-methyl-D-aspartate receptor

K Takahata, H Katsuki, T Kume, K Ito, Y Tochikawa, S Muraoka, F Yoneda, S Kashii, Y Honda, A Akaike

JOURNAL OF PHARMACOLOGICAL SCIENCES (2003)

Article Ophthalmology

Retinal neuronal death induced by intraocular administration of a nitric oxide donor and its rescue by neurotrophic factors in rats

K Takahata, H Katsuki, T Kume, D Nakata, K Ito, S Muraoka, F Yoneda, S Kashii, Y Honda, A Akaike

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2003)

Article Behavioral Sciences

Photomodulatory effects in the hypothalamus of sleep-deprived young and aged rats

Radwa H. Lutfy, Sherine Abdel Salam, Haitham S. Mohammed, Marwa M. Shakweer, Amina E. Essawy

Summary: Insufficient sleep is associated with impaired hypothalamic activity and declined attentional performance. This study found that near-infrared (NIR) laser therapy can alleviate the effects of sleep deprivation on the hypothalamus, enhance antioxidant status, suppress neuroinflammation, and regulate cellular activity.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

N-acetylcysteine ameliorates chemotherapy-induced impaired anxiety and depression-like behaviors by regulating inflammation, oxidative and cholinergic status, and BDNF release

Durmus Ali Aslanlar, Emin Fatih Visneci, Mehmet Oz, K. Esra Nurullahoglu Atalik

Summary: Mood disorders caused by chemotherapy have become more important as cancer patients' survival increases. This study used methotrexate to induce mood disorders in rats and found that treatment with the antioxidant N-acetylcysteine (NAC) can alleviate anxiety and depression-like behaviors, increase antioxidant capacity, reduce oxidative stress and inflammatory response, and regulate brain chemistry. The findings suggest that NAC treatment could be an effective strategy in revising the treatment for individuals suffering from chemotherapy-induced mood disorders.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Continuous high-frequency repetitive transcranial magnetic stimulation at extremely low intensity affects exploratory behavior and spatial cognition in mice

Yunfan Zhang, Yunbin Zhang, Zhuangfei Chen, Ping Ren, Yu Fu

Summary: This study systematically investigated the effects of extremely low intensity HF-rTMS on cognition in mice and found that 40 Hz rTMS significantly impaired exploratory behavior and spatial memory at both 10 mT and 1 mT conditions. Additionally, 40 Hz stimulation had remarkably different effects on exploratory behavior depending on intensity, compared to 10 Hz stimulation.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Alterations in regional homogeneity and functional connectivity in the cerebellum of patients with sporadic amyotrophic lateral sclerosis

Xuan Xuan, Guangling Zheng, Wenjia Zhu, Qionghua Sun, Yawei Zeng, Juan Du, Xusheng Huang

Summary: This study examines the functional characteristics of the cerebellum in individuals with sALS and their correlation with clinical data. The results show changes in both local and global functional connectivity in the cerebellum of sALS patients, suggesting a pathophysiological role of the cerebellum in sALS.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Clinical effects of anodal tDCS and identifying response markers in post-traumatic stress disorder (PTSD): An open-label study

Mehdi Rezaei, Mohammad Mahdi Shariat Bagheri

Summary: This study examined the efficacy of tDCS for PTSD and related symptoms, as well as the factors that may predict response to tDCS. The results showed that tDCS had a positive effect in reducing symptoms of PTSD, depression, anxiety, and anhedonia. The severity of symptoms at baseline may also predict the response to tDCS.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Self-esteem and cortical thickness correlate with aggression in healthy children: A surface-based analysis

Huimin Wu, Yiqun Guo, Yaoyao Zhang, Le Zhao, Cheng Guo

Summary: Aggression can have serious consequences, but little is known about its personality and neurological origins in children. This study investigated the relationship between self-esteem, aggression, and brain structure in healthy children, and found that self-esteem was negatively associated with aggression. The study also revealed that increased cortical thickness in certain brain areas may be a potential mechanism linking low self-esteem to aggression in children.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Parental involvement affects parent-adolescents brain-to-brain synchrony when experiencing different emotions together: An EEG-based hyperscanning study

Xinmei Deng, Kexin Chen, Xiaoming Chen, Lin Zhang, Mingping Lin, Xiaoqing Li, Qiufeng Gao

Summary: Parental involvement affects the relationship and communication between parents and adolescents. This study found that high parental involvement is associated with stronger brain-to-brain synchrony during shared positive emotional experiences, while low parental involvement is associated with stronger synchrony during shared negative emotional experiences.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Role of serotonin in the lack of sensitization caused by prolonged food deprivation in Aplysia

Xin Deng, I. -Shuo Huang, Kourtlin Williams, Marcy L. Wainwright, Paul Zimba, Riccardo Mozzachiodi

Summary: Food deprivation can lead to neurological dysfunctions, including memory impairment. This study used Aplysia as an animal model to investigate the memory deficits caused by prolonged food deprivation. The results showed that 14 days of food deprivation decreased the level of 5-HT in the hemolymph, which contributed to the lack of sensitization and its cellular correlates. However, exogenous application of 5-HT partially induced sensitization in the food deprived animals.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

The effects of a dual orexin receptor antagonist on fear extinction memory and sleep in mice: Implications for exposure therapy

Ihori Kobayashi, Patrick A. Forcelli

Summary: The study found that intervention with the dual orexin receptor antagonist suvorexant did not have the expected effects on extinction memory and sleep. Higher percentages of REM sleep were associated with poorer extinction memory recall and stronger fear responses. Additionally, the fear extinction training protocol used in this study did not lead to complete fear extinction.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Nicotinamide mononucleotide pretreatment improves long-term isoflurane anesthesia-induced cognitive impairment in mice

Jiyan Xu, Xinlu Chen, Shuai Liu, Ziqi Wei, Minhui Xu, Linhao Jiang, Xue Han, Liangyu Peng, Xiaoping Gu, Tianjiao Xia

Summary: This study investigated the effects of nicotinamide mononucleotide (NMN) on oxidative stress and cognitive function in postoperative cognitive dysfunction (POCD) mice. The results showed that NMN pretreatment reduced oxidative stress damage and alleviated cognitive impairment in POCD mice.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Coordination function index: A novel indicator for assessing hindlimb locomotor recovery in spinal cord injury rats based on catwalk gait parameters

Song Liu, Qiang Wu, Liyue Wang, Cong Xing, Junrui Guo, Baicao Li, Hongpeng Ma, Hao Zhong, Mi Zhou, Shibo Zhu, Rusen Zhu, Guangzhi Ning

Summary: In this study, a systematic assessment indicator was developed to objectively evaluate hindlimb motor function recovery in rats after thoracic contusion SCI. By screening CatWalk XT gait parameters and using exploratory factor analysis, 38 suitable parameters for assessing motor function were identified. A reliable Coordinated Function Index (CFI) was proposed based on these parameters and simplified for improved assessment efficacy.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Transcranial alternating current stimulation does not affect microscale learning

Kyosuke Shiga, Shota Miyaguchi, Yasuto Inukai, Naofumi Otsuru, Hideaki Onishi

Summary: This study aimed to investigate the effects of transcranial alternating current stimulation (tACS) on microscale learning in implicit motor tasks. Contrary to expectations, the results showed that the stimulation protocol had no significant effects on microscale learning, revealing a novel aspect of microscale learning in implicit motor tasks.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Protective effect of vitamin D on learning and memory impairment in rats induced by high fructose corn syrup

Cahide Aslan, Rahime Aslankoc, Ozlem Ozmen, Buse Nur Suluk, Oguzhan Kavrik, Nurhan Gumral

Summary: This study examined the negative effects of high fructose corn syrup on prefrontal cortex damage in adolescent rats, as well as the protective role of vitamin D.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Orexin receptors in the hippocampal dentate gyrus modulated the restraint stress-induced analgesia in the animal model of chronic pain

Matin Baghani, Arad Bolouri-Roudsari, Reyhaneh Askari, Abbas Haghparast

Summary: The study suggests that the orexinergic system in the dentate gyrus region of the brain may act as an endogenous pain control system and a potential target for treating stress-related disorders.

BEHAVIOURAL BRAIN RESEARCH (2024)

Article Behavioral Sciences

Low-dose Esketamine suppresses NLRP3-mediated apoptotic and pyroptotic cell death in microglial cells to ameliorate LPS-induced depression via ablating GSK-3β

Sen Zhou, Yang Liu, Binbin Xue, Peigen Yuan

Summary: This study confirmed that low-dose Esketamine alleviates LPS-induced depressive symptoms by regulating the GSK-3 beta/NLRP3 pathway. Appropriate doses of Esketamine are essential for the treatment of depression in the clinical setting.

BEHAVIOURAL BRAIN RESEARCH (2024)