Article
Neurosciences
Sarthak M. Singhal, Vivien Zell, Lauren Faget, Lauren M. Slosky, Lawrence S. Barak, Marc G. Caron, Anthony B. Pinkerton, Thomas S. Hnasko
Summary: The strong expression of NTR1 in VTA DA neurons and terminals makes it an attractive target to modulate DA neuron activity and normalize DA-related pathologies. SBI-553 acts as a positive allosteric modulator of NTR1 beta-arrestin recruitment and antagonizes NTR1 Gq protein signaling. It blunts NT's effects on spontaneous DA neuron firing, D2 auto-receptor function, and DA release without independently affecting these measures.
Article
Anatomy & Morphology
Imre Kallo, Azar Omrani, Frank J. Meye, Han de Jong, Zsolt Liposits, Roger A. H. Adan
Summary: Orexin neurons play a role in homeostatic regulatory processes and provide input to VTA, a central hub processing reward and motivation. This study found that the VTA neurons projecting to the mNAcs receive more input from orexin neurons compared to those projecting to the mPFC. Orexin exerts facilitatory effects on both clusters of dopamine neurons.
BRAIN STRUCTURE & FUNCTION
(2022)
Article
Cell Biology
Karolina Farrell, Armin Lak, Aman B. Saleem
Summary: Midbrain dopamine neurons encode reward prediction error signals to improve goal-directed navigation.
Review
Biochemistry & Molecular Biology
Yu Liu, Gavan P. McNally
Summary: Dopamine plays a crucial role in relapse to drug seeking, with different forms of relapse being driven by distinct dopamine mechanisms. Understanding the diverse dopamine pathways involved in relapse behaviors is essential for developing effective strategies to prevent relapse.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Ming Sun, Chao Wu, Lixin Liu, Liang Gu, Zihao Wang, Feng Xu, Donglin Zhu
Summary: The brain renin-angiotensin system (RAS) is involved in substance abuse and addiction. The two arms of RAS, ACE1/Ang II/AT1R axis and ACE2/Ang(1-7)/MasR axis, are disrupted in the ventral tegmental area (VTA) during alcohol addiction. The dysregulated RAS in the VTA stimulates oxidative stress and dopaminergic neurotransmission, contributing to alcohol addiction.
BIOCHEMICAL PHARMACOLOGY
(2023)
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
Zhixiong He, Lizi Zhang, Wenjuan Hou, Xin Zhang, Larry J. Young, Laifu Li, Limin Liu, Huan Ma, Yufeng Xun, Zijian Lv, Yitong Li, Rui Jia, Jingang Li, Fadao Tai
Summary: Paternal care is crucial for the development of offspring in monogamous species, and the activation of oxytocin neurons in the PVN to VTA or NAc plays a significant role in promoting paternal care. Understanding the neuronal circuitry underlying paternal care could have implications for treating abnormalities such as paternal postpartum depression or abuse.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Daniel R. Garton, Giorgio Turconi, Vilma Iivanainen, Jaan-Olle Andressoo
Summary: Cocaine addiction is a serious and deadly condition without effective pharmacological treatments. The neurotrophic factor GDNF and its receptor RET may be a promising approach to treating psychostimulant addiction. In this study, reducing RET expression in the VTA accelerates extinction of conditioned place preference and reduces reinstatement, while reducing GDNF in the NAc prolongs conditioned place preference and increases preference during reinstatement. This suggests that RET antagonism in the VTA and intact or enhanced GDNF function in the NAc could be a new approach for treating cocaine addiction.
Article
Integrative & Complementary Medicine
Hanqing Xi, Wenzhong Wu, Shan Qin, Xiaoqiu Wang, Chengyong Liu
Summary: After chronic sleep deprivation, rats showed increased autonomous activity and excitability of the VTA-NAc dopamine pathway, resulting in increased dopamine content in the VTA and NAc, increased expression of D1R in the NAc, and decreased expression of D2R. EA can reduce the autonomous ability of CSD rats, decrease dopamine content in the VTA and NAc, decrease expression of D1R in the NAc, and increase expression of D2R. The therapeutic effect of EA in chronic insomnia may be mediated by reducing excitability of the VTA-NAc DA pathway.
ACUPUNCTURE IN MEDICINE
(2023)
Article
Neurosciences
J. Daniel Obray, Christina A. Small, Emily K. Baldwin, Eun Young Jang, Jin Gyeom Lee, Chae Ha Yang, Jordan T. Yorgason, Scott C. Steffensen
Summary: This study found that peripherally administered dopamine can enhance dopamine levels in the nucleus accumbens and modulate related behaviors. Dopamine subtype-2 receptors are involved in this process and can influence dopamine neuron activity.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Angela M. Lee, Mohammad Shahid Mansuri, Rashaun S. Wilson, TuKiet T. Lam, Angus C. Nairn, Marina R. Picciotto
Summary: Significant sex differences in the proteome of the mesolimbic system at baseline and after nicotine reward or withdrawal were identified, which may help explain the differential trajectories and susceptibility to nicotine addiction in males and females.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(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
Anesthesiology
Wenjie Ren, Maria Virginia Centeno, Xuhong Wei, Ian Wickersham, Marco Martina, A. Vania Apkarian, D. James Surmeier
Summary: The nucleus accumbens and the ventral tegmental area play crucial roles in shaping chronic pain states by altering functional connectivity and dopamine signaling. Adaptive changes induced by SNI in these regions can alleviate anxiety and social withdrawal, but countervailing mechanisms may contribute to the chronic pain state.
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
Valentina Bassareo, Roberto Frau, Riccardo Maccioni, Pierluigi Caboni, Cristina Manis, Alessandra T. Peana, Rossana Migheli, Simona Porru, Elio Acquas
Summary: The addictive potential of ethanol is triggered by the activation of DA neurons in the pVTA projecting to the ipsilateral AcbSh, leading to an increase in DA release. The generation of salsolinol in the pVTA is responsible for the increase in AcbSh DA release via mu OR stimulation, providing grounds for developing preventive and therapeutic strategies.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
David M. Bortz, Anthony A. Grace
NEUROPSYCHOPHARMACOLOGY
(2018)
Article
Neurosciences
Susan F. Sonnenschein, Kathryn M. Gill, Anthony A. Grace
NEUROPSYCHOPHARMACOLOGY
(2019)
Review
Neurosciences
Susan F. Sonnenschein, Anthony A. Grace
Review
Endocrinology & Metabolism
Millie Rincon-Cortes, Anthony A. Grace
FRONTIERS IN NEUROENDOCRINOLOGY
(2020)
Article
Neurosciences
Xiyu Zhu, Anthony A. Grace
Summary: This study found that early environmental enrichment (EE) in prepubertal rats can prevent dopamine hyperresponsivity in the MAM model of schizophrenia, as measured by electrophysiological recordings and locomotor response to amphetamine. EE normalized excessive firing in the ventral hippocampus without affecting anxiety-like behaviors and basolateral amygdala firing, indicating its potential as a preventative approach for schizophrenia.
BIOLOGICAL PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Felipe V. Gomes, Anthony A. Grace
Summary: Although currently available antipsychotic drugs can reduce psychotic symptoms in schizophrenia patients, they have numerous side effects and are not effective against negative and cognitive symptoms. Developing new drugs that target the excitatory/inhibitory balance in the brain may offer a more effective approach in treating schizophrenia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Psychiatry
Susan F. Sonnenschein, Anthony A. Grace
Summary: The study found that peripubertal administration of POM in MAM rats can prevent the emergence of vHPC pyramidal neuron hyperactivity and increased DA neuron population activity in adulthood, showing potential for preventing dopamine system dysfunction and psychosis development. However, POM did not show significant differences in SAL rats.
SCHIZOPHRENIA BULLETIN
(2021)
Article
Clinical Neurology
Jillian J. Weeks, Anthony A. Grace, Alan F. Sved
Summary: The study showed that both acute and chronic administration of nicotine improved deficits in schizophrenia-like behaviors and normalized neuronal activity in specific brain regions in the schizophrenia rodent model. These findings support the self-medication hypothesis for smoking in schizophrenia and suggest the potential of nicotinic modulation in future pharmacotherapies.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Clinical Neurology
Laszlo Peczely, Tamas Ollmann, Kristof Laszlo, Laszlo Lenard, Anthony A. Grace
Summary: Quinpirole dose dependently regulates VTA dopaminergic activity and influences motivation and motor behavior in rats at the level of the ventral pallidum.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiyu Zhu, Anthony A. Grace
Summary: Adolescent stress is a risk factor for schizophrenia, and its effects on neurobiological activity and impairment vary depending on age and sex. Understanding these differences could provide insights into the underlying mechanisms of stress-related psychopathologies and guide targeted interventions.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychiatry
Andreza M. Cavichioli, Thamyris Santos-Silva, Anthony A. Grace, Francisco S. Guimaraes, Felipe Gomes
Summary: This study suggests that levetiracetam can attenuate the adverse outcomes associated with schizophrenia caused by stress during adolescence, by reversing the behavioral changes, ventral hippocampus hyperactivity, and enhanced ventral tegmental area dopamine system activity.
SCHIZOPHRENIA BULLETIN
(2023)
Article
Clinical Neurology
David M. Bortz, Catalina M. Feistritzer, Anthony A. Grace
Summary: This study suggests that the medial prefrontal cortex (mPFC) to medial septum (MS) pathway may be involved in regulating cognitive flexibility and dopamine neuron activity. Activation of the mPFC-MS pathway improves strategy switching, while inhibition produces different effects. The pathway bidirectionally regulates dopamine neuron activity. This study reveals a potential top-down circuit from the prefrontal cortex to the midbrain that can manipulate dopamine activity to promote cognitive flexibility.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Anthony A. Grace, Daniela L. Uliana
Summary: Therapeutic intervention for schizophrenia relies on blockade of dopamine D2 receptors to alleviate symptoms. However, an overactive hippocampus is the primary driver of dopamine system hyper-responsiveness. Antipsychotic drugs alleviate symptoms by causing depolarization block, but they also activate multiple synapses downstream from the site of pathology. A novel class of drugs targeting the hippocampal overdrive could be more effective and better tolerated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Xiyu Zhu, Anthony A. Grace
Summary: This study presents a protocol for delivering environmental enrichment in discrete postnatal windows to prevent long-term dopamine neuron dysfunctions in a neurodevelopmental rat model of schizophrenia risk. It describes the generation of the schizophrenia model through prenatal treatment and the application of EE paradigms on male rats at different ages. Control groups in regular environment cages are also included for comparison.
Article
Psychiatry
David M. Bortz, Anthony A. Grace