Article
Pharmacology & Pharmacy
Maryam Majidinezhad, Haleh Amirteymouri, Saeideh Karimi-haghighi, Masoumeh Kourosh-Arami, Abbas Haghparast
Summary: The study reveals that OX receptors in the ventral tegmental area (VTA) play a crucial role in the acquisition and expression phases of METH-induced conditioned place preference (CPP).
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Beibei Peng, Qikuan Xu, Jing Liu, Sophie Guo, Stephanie L. Borgland, Shuai Liu
Summary: The study found that chronic corticosteroid treatment induces anxiety-like behavior and impairs food-seeking behavior. Additionally, chronic CORT treatment decreases excitability and excitatory synaptic transmission onto VTA dopamine neurons, while increasing somatodendritic dopamine concentration. Restoring D2R signaling in the VTA can ameliorate these deficits induced by chronic CORT exposure.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Gemma Navarro, William Rea, Cesar Quiroz, Estefania Moreno, Devan Gomez, Cody J. Wenthur, Vicent Casado, Lorenzo Leggio, Matthew C. Hearing, Sergi Ferre
Summary: GHS-R1b facilitates oligomerization with GHS-R1a, impacting its pharmacological properties, but GHSR1a:GHS-R1b:D1R oligomers in the VTA are the main mediators of the dopaminergic effects of ghrelin.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Sheila A. Engi, Erin J. Beebe, Victoria M. Ayvazian, Fabio C. Cruz, Joseph F. Cheer, Jennifer M. Wenzel, Natalie E. Zlebnik
Summary: Mesolimbic dopamine plays a crucial role in motivated behavior, with CB1 receptor signaling in the VTA being implicated in the phasic activation of dopamine. Cocaine-induced increases in motivation appear to require 2-AG signaling at CB1 receptors in the VTA, suggesting potential cannabinoid-based pharmacotherapeutic targets for substance abuse treatment.
Article
Neurosciences
Akira Mizoguchi, Ryoichi Banno, Runan Sun, Hiroshi Yaginuma, Keigo Taki, Tomoko Kobayashi, Mariko Sugiyama, Taku Tsunekawa, Takeshi Onoue, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Shintaro Iwama, Hidetaka Suga, Hiroshi Arima
Summary: This study found that high-fat diet induced inflammation in the VTA area, leading to insulin resistance and increased microglial activation. Subsequent research revealed that the inflammation induced by HFD in the VTA is associated with dysfunction of the reward system and insulin resistance.
Article
Medicine, Research & Experimental
Marie A. Doyle, Michelle S. Mazei-Robison
Summary: Opioid drugs are valued for their pain-relieving properties but pose significant risks due to abuse potential. Long-term use of opioids can lead to molecular changes in VTA dopamine neurons, which are associated with addiction-related behaviors. Future research should focus on identifying whether these neuroadaptations are specific to certain subpopulations of VTA DA neurons.
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2021)
Article
Behavioral Sciences
Everett Altherr, Aundrea Rainwater, Darian Kaviani, Qijun Tang, Ali D. Guler
Summary: The study suggests that long-term consumption of a high-fat diet reduces preference and consumption of high-calorie foods, associated with changes in mesolimbic dopamine signaling, and these changes can be mitigated by exercise.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Ken T. Wakabayashi, Malte Feja, Martin P. K. Leigh, Ajay N. Baindur, Mauricio Suarez, Paul J. Meyer, Caroline E. Bass
Summary: Targeted activation of mesoaccumbal GABA neurons decreases responding to incentive cues associated with smaller-than-expected rewards, facilitating adaptation in reward-seeking behaviors. In contrast, activating all ventral tegmental area GABA neurons results in a uniform decrease in responding to incentive cues regardless of changes in reward size, indicating a specific role of mesoaccumbal GABA projections in associative learning processes.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Chen Lu, Yifan Feng, Hongxia Li, Zilong Gao, Xiaona Zhu, Ji Hu
Summary: This study investigates the neural mechanism behind deep brain stimulation (DBS) in alleviating positive psychotic-like behaviors. The researchers stimulated the ventral tegmental area (VTA) in mice and found that it activated local GABA and dopamine neurons, reducing hyperlocomotion and relieving stereotyped behaviors induced by MK-801 injection. Optogenetic manipulation further confirmed the involvement of VTA GABA neurons in alleviating these behaviors. This preclinical study provides insights into the mechanism of DBS and supports its potential clinical application in treating psychotic diseases.
FRONTIERS IN HUMAN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Grazyna Jerzemowska, Karolina Plucinska, Aleksandra Piwka, Magdalena Podlacha, Jolanta Orzel-Gryglewska
Summary: In this study, the researchers investigated the role of opioid receptors (OR) in the pedunculopontine tegmental nucleus (PPN) in regulating motivated behaviors. They found that activation and blocking of OR in the PPN affected behavioral and neuronal activity, modulating the reward system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Jicheng Li, Renfei Fan, Xiaofeng Liu, Xiangfeng Shen, Xin Liu, Hua Zhao
Summary: The study found that most neurons in LHb are aversion-activated and reward-inhibited, mainly composed of glutamatergic neurons, while most neurons in VTA are reward-activated and aversion-inhibited, inhibited by glutamatergic neurons in LHb. Optogenetic activation or inhibition of glutamatergic neurons in LHb and their terminals in VTA could induce aversive or reward behaviors.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biology
Kevin Beier
Summary: This study used a modified viral-genetic strategy to investigate both local and long-range inputs to dopamine cells in the ventral tegmental area (VTA) in mice. The findings revealed that nearly half of the inputs to VTA cells are located locally, which were previously overlooked. The main source of inhibition to VTA cells is from the substantia nigra pars reticulata, with substantial contributions from the VTA and substantia nigra pars compacta. Dopamine neurons also have connections with other dopamine neurons within the VTA and the nearby retrorubal field. Additionally, the study showed that VTA neurons receive inputs from serotonergic neurons distributed throughout the midbrain and hindbrain, with the majority coming from the dorsal raphe.
Article
Multidisciplinary Sciences
Marta E. Soden, Joshua X. Yee, Larry S. Zweifel
Summary: This study reveals that fast-acting neurotransmitters and slow, modulatory neuropeptides can co-regulate neural circuit outputs through different signaling pathways. By using a genetic-based anatomical disconnect procedure, researchers were able to independently edit neurotransmitter- and neuropeptide-related genes in specific cell types. It was found that the neurotransmitter GABA and the neuropeptide neurotensin work together to regulate dopamine neuron responses and optimize behavior.
Article
Anatomy & Morphology
Jacques P. P. Flores-Dourojeanni, Marleen H. H. van den Munkhof, Mieneke C. M. Luijendijk, Louk J. M. J. Vanderschuren, Roger A. H. Adan
Summary: Inhibiting the synaptic transmission from the ventral tegmental area (VTA) to the nucleus accumbens shell (NAcbS) using optogenetics induces exaggerated impulsive actions in the five-choice serial reaction time task (5-CSRTT), without affecting attentional or motivational parameters.
BRAIN STRUCTURE & FUNCTION
(2023)
Article
Geriatrics & Gerontology
Pedro A. Pereira, Joana Coelho, Ana Silva, M. Dulce Madeira
Summary: Studies have shown that with age, there is no significant change in the number and size of dopamine neurons in the VTA of rats, but the cholinergic input decreases, while the cholinergic neurons in the PPT and LDT nuclei increase in size. These results suggest that dysfunction of the cholinergic system may contribute to the age-related deterioration of the brain reward system.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bolati Wulaer, Kazuo Kunisawa, Kazuhiro Hada, Willy Jaya Suento, Hisayoshi Kubota, Tsubasa Iida, Aika Kosuge, Taku Nagai, Kiyofumi Yamada, Atsumi Nitta, Yasuko Yamamoto, Kuniaki Saito, Akihiro Mouri, Toshitaka Nabeshima
Summary: Deficiency of Shati/Nat8l affects neurogenesis and attentional behavior in mice, possibly through modulation of dopaminergic transmission.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
You-Hsin Lin, Yukie Yamahashi, Keisuke Kuroda, Omar Faruk, Xinjian Zhang, Kiyofumi Yamada, Akihiro Yamanaka, Taku Nagai, Kozo Kaibuchi
Summary: The study revealed that accumbal D2R-MSNs regulate negative reinforcement through the A2aR-PKA-Rap1-MEK pathway. Inhibition of this pathway has been shown to attenuate aversive responses.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Yumi Tsuneura, Masahito Sawahata, Norimichi Itoh, Ryoya Miyajima, Daisuke Mori, Takao Kohno, Mitsuharu Hattori, Akira Sobue, Taku Nagai, Hiroyuki Mizoguchi, Toshitaka Nabeshima, Norio Ozaki, Kiyofumi Yamada
Summary: Reelin, a crucial extracellular matrix protein secreted by Cajal-Retzius cells, plays important roles in brain development and neuronal functions. Reductions in Reelin are associated with brain dysfunctions in mental disorders like schizophrenia. A recent study identified a novel deletion in RELN encoding Reelin in Japanese schizophrenia patients, leading to abnormalities in brain structures and social behavior.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Review
Biochemistry & Molecular Biology
Tsuyoshi Nakai, Kiyofumi Yamada, Hiroyuki Mizoguchi
Summary: Alzheimer's disease is an age-related and progressive neurodegenerative disorder mainly caused by the accumulation of Aβ and tau. Despite various AD mouse models developed, none fully replicate all pathologies present in human AD. APP knock-in mice may offer a better evaluation of candidate therapeutics in early-stage AD mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Behavioral Sciences
Jingzhu Liao, Geyao Dong, Bolati Wulaer, Masahito Sawahata, Hiroyuki Mizoguchi, Daisuke Mori, Norio Ozaki, Toshitaka Nabeshima, Taku Nagai, Kiyofumi Yamada
Summary: The study found that Reln-del mice exhibited delayed learning in visual discrimination and reversal learning tasks, but their behavioral flexibility remained unaffected.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Yumi Tsuneura, Tsuyoshi Nakai, Hiroyuki Mizoguchi, Kiyofumi Yamada
Summary: Reelin, an important protein for brain development and function, is found to be associated with neuropsychiatric disorders. Supplementing Reelin could improve learning and neuronal dysfunctions in animal models. Therefore, studying the role of Reelin in neuropsychiatric disorders and potential therapeutic approaches is of great significance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Md Omar Faruk, Daisuke Tsuboi, Yukie Yamahashi, Yasuhiro Funahashi, You-Hsin Lin, Rijwan Uddin Ahammad, Emran Hossen, Mutsuki Amano, Tomoki Nishioka, Anastasios Tzingounis, Kiyofumi Yamada, Taku Nagai, Kozo Kaibuchi
Summary: The nucleus accumbens (NAc) plays crucial roles in emotional behaviors, and muscarinic signaling induces the phosphorylation of KCNQ2 at T217 via PKC activation for aversive learning. Electric foot shock and donepezil can induce this phosphorylation, while an M1R antagonist can suppress this process.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Tetsuo Matsuzaki, Yoshiaki Kato, Hiroyuki Mizoguchi, Kiyofumi Yamada
Summary: This study developed a predictive model for initial vancomycin dosing using machine learning, and compared its performance with experts, another machine learning model, and commonly used dosing software. The results showed that our model had a comparable target attainment rate to experts, and it could assist in decision making for initial dosing in the absence of dose planning consultations.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mizuki Uchida, Yukihiro Noda, Sho Hasegawa, Hirotake Hida, Masayuki Taniguchi, Akihiro Mouri, Akira Yoshimi, Toshitaka Nabeshima, Kiyofumi Yamada, Tomomi Aida, Kohichi Tanaka, Norio Ozaki
Summary: The study found that GLAST plays an important role in regulating cognitive and emotional behaviors in mice during neurodevelopment. Dysfunction of early postnatal glutamatergic facilitation by GLAST leads to cognitive and emotional abnormalities, primarily manifested as neurotransmission dysfunction and morphological changes.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Cell Biology
Rijwan Uddin Ahammad, Tomoki Nishioka, Junichiro Yoshimoto, Takayuki Kannon, Mutsuki Amano, Yasuhiro Funahashi, Daisuke Tsuboi, Md. Omar Faruk, Yukie Yamahashi, Kiyofumi Yamada, Taku Nagai, Kozo Kaibuchi
Summary: Protein phosphorylation plays a critical role in intracellular signaling pathways and physiological functions in the brain. Dysregulation of these pathways is associated with neurodevelopmental disorders. This study developed an online database to provide information on phosphorylation signals and analyzed related pathways.
Review
Biochemistry & Molecular Biology
Xinjian Zhang, Daisuke Tsuboi, Yasuhiro Funahashi, Yukie Yamahashi, Kozo Kaibuchi, Taku Nagai
Summary: Dopamine regulates emotional behaviors, including rewarding and aversive behaviors, through the mesolimbic dopaminergic pathway. Protein phosphorylation plays a critical role in intracellular signaling pathways and physiological functions, and dopamine regulates neuronal excitability and synaptic plasticity through phosphorylation of intracellular substrates. Understanding the mechanisms by which dopamine controls emotional behaviors is crucial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xinjian Zhang, Kiyoyuki Kitaichi, Akihiro Mouri, Xinzhu Zhou, Toshitaka Nabeshima, Kiyofumi Yamada, Taku Nagai
Summary: Although opioids have clinical benefits as analgesics, their misuse and addiction are on the rise. This study investigated the optimal ratio of an opioid and the opioid receptor antagonist, naloxone, in abuse-deterrent formulations. The conditioned place preference test showed that naloxone effectively inhibited the rewarding effects induced by opioids. The study suggests that the ratio of naloxone with opioids can serve as an index for developing abuse-deterrent formulations.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)