Article
Pharmacology & Pharmacy
Lucia Caffino, Francesca Mottarlini, Giorgia Targa, Michel M. M. Verheij, Fabio Fumagalli, Judith R. Homberg
Summary: This study investigates the influence of SERT deletion on glutamate homeostasis in the NAc, and finds that SERT deletion leads to a reduction in glutamate signaling and further dysregulation in the glutamatergic synapse after cocaine self-administration.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Lucia Caffino, Francesca Mottarlini, Giorgia Targa, Michel M. M. Verheij, Judith Homberg, Fabio Fumagalli
Summary: The study found that the deletion of serotonin transporter (SERT) may sensitize the glutamatergic synapses of the nucleus accumbens core to long-term but not short-term intake of cocaine.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Benjamin M. Siemsen, Sarah M. Barry, Kelsey M. Vollmer, Lisa M. Green, Ashley G. Brock, Annaka M. Westphal, Raven A. King, Derek M. DeVries, James M. Otis, Christopher W. Cowan, Michael D. Scofield
Summary: This study identified and characterized a specific subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. These neurons play a crucial role in regulating cue-induced cocaine seeking behavior, but not sucrose seeking. Additionally, they undergo morphological changes during the peak of cocaine seeking. These findings provide insights into the neural mechanisms of drug relapse and offer a novel target for addiction therapeutics.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Ma Luisa Soto-Montenegro, Veronica Garcia-Vazquez, Nicolas Lamanna-Rama, Gonzalo Lopez-Montoya, Manuel Desco, Emilio Ambrosio
Summary: Vulnerability to addiction is associated with the risk of developing an addiction during an individual's lifetime. This study used PET and SPM techniques to investigate changes in brain glucose metabolism in response to chronic morphine self-administration in two rat strains with different vulnerability to drug abuse. The results showed significant differences in brain metabolic patterns between the two strains, suggesting variations in the efficiency of neural substrates in translating the effects of the drug.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Jason Yuen, Abhinav Goyal, Aaron E. Rusheen, Abbas Z. Kouzani, Michael Berk, Jee Hyun Kim, Susannah J. Tye, Charles D. Blaha, Kevin E. Bennet, Dong-Pyo Jang, Kendall H. Lee, Hojin Shin, Yoonbae Oh
Summary: For over 40 years, in vivo microdialysis techniques have been crucial in studying the effects of illicit substances on dopamine levels in the brain, but limitations have led to the development of a new electrochemical method known as M-CSWV. This method provides faster recordings of dopamine level changes, allowing for a more detailed understanding of neuronal responses to drug administration.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biology
Ruud van Zessen, Yue Li, Lucile Marion-Poll, Nicolas Hulo, Jerome Flakowski, Christian Luscher
Summary: LS is an early behavioral adaptation to addictive drugs, driven by increased dopamine in the NAc. During cocaine LS, D1R SPN activity increases while D2R SPN activity decreases, with a higher number of neurons responding in opposite directions. Inhibition of the ERK signaling pathway reduces the number of cocaine responsive D1R SPNs, indicating a dynamic dichotomy in accumbal population activity.
Article
Neurosciences
Kelle E. Nett, Alexa R. Zimbelman, Matthew S. McGregor, Vanessa Alizo Vera, Molly R. Harris, Ryan T. LaLumiere
Summary: Previous evidence suggests that the infralimbic cortex (IL) plays a role in inhibiting cocaine seeking behavior in rats. In this study, the researchers investigated whether IL activity and its outputs to the nucleus accumbens shell (NAshell) and amygdala are involved in encoding extinction contingencies following cocaine self-administration. They used optogenetic techniques to silence IL-NAshell or IL-amygdala activity after an unreinforced lever press during extinction training and found that inhibition of IL-NAshell or IL-amygdala activity impaired extinction retention.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Tong-Yu Liang, Hua Zhou, Yan-Gang Sun
Summary: Ventral tegmental area (VTA) dopaminergic neurons participate in itch processing through their projection to the nucleus accumbens (NAc). The roles of dopamine receptor subtypes in different subregions of the NAc during itch processing were investigated. It was found that dopamine D1 receptors (D1R) blockade in the lateral shell (LaSh) impaired pruritogen-induced scratching behavior, while D2R activation in both LaSh and medial shell (MeSh) attenuated scratching behavior. Dopamine release in LaSh was elevated during scratching behavior, suggesting a motivational component of itch processing. This study highlights the importance of D1R in the LaSh of the NAc in itch signal processing.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Daniel J. Christoffel, Jessica J. Walsh, Paul Hoerbelt, Boris D. Heifets, Pierre Llorach, Ricardo C. Lopez, Charu Ramakrishnan, Karl Deisseroth, Robert C. Malenka
Summary: The study reveals that dopamine and serotonin modulate excitatory synaptic transmission in the nucleus accumbens in input-specific ways, influencing motivated behaviors differently. Endogenous release of DA and 5-HT, as well as optogenetic inhibition, alter the behavioral effects of drugs in distinct manners.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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
Neurosciences
Dan P. Covey, Edith Hernandez, Miguel A. Lujan, Joseph F. Cheer
Summary: The study found that dopamine release in the nucleus accumbens responds differently to cues signaling increasing cost of reward. Endocannabinoid signaling facilitates goal-seeking and nucleus accumbens dopamine release, while chronic MAGL treatment stably facilitates goal-seeking and dopamine encoding without the development of tolerance.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Behavioral Sciences
David Lindenbach, Giada Vacca, Soyon Ahn, Jeremy K. Seamans, Anthony G. Phillips
Summary: This study found that the glutamatergic vSub-NAc pathway can modulate food-seeking behavior, including 'response vigor', depending on the present motivational state. In a 'low-motivational state' following failure to achieve an anticipated reward, optogenetic activation of this pathway can reinvigorate lever-pressing behavior. Conversely, inhibition of this pathway appears to decrease motivated responding.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Neurosciences
Carla L. Busceti, Roxana P. Ginerete, Luisa Di Menna, Giovanna D'Errico, Francesca Cisani, Paola Di Pietro, Tiziana Imbriglio, Valeria Bruno, Giuseppe Battaglia, Francesco Fornai, James A. Monn, Anna Pittaluga, Ferdinando Nicoletti
Summary: Genetic knockout of mGlu2 and mGlu3 receptors affects mice's preference and motor responses to methamphetamine, indicating different roles of these two receptors in methamphetamine addiction. mGlu3(-/-) mice show increased sensitization and elevated levels of phospho-ERK1/2 and free radicals in relevant brain areas, while mGlu2(-/-) mice exhibit reduced motor response to the first methamphetamine injection.
Article
Cell Biology
Wei Wang, Xueyi Xie, Xiaowen Zhuang, Yufei Huang, Tao Tan, Himanshu Gangal, Zhenbo Huang, William Purvines, Xuehua Wang, Alexander Stefanov, Ruifeng Chen, Lucas Rodriggs, Anita Chaiprasert, Emily Yu, Valerie Vierkant, Michelle Hook, Yun Huang, Emmanuel Darcq, Jun Wang
Summary: Withdrawal from chronic opioid use leads to hypodopaminergic states and negative affect, promoting relapse. Activation of MORs in dMSNs in the striatal patch compartment suppresses striatopallidal transmission, and withdrawal potentiated this transmission. Fentanyl self-administration enhances striatonigral transmission and reduces dopaminergic activity, while activated striatal neurons mediate contextual memory retrieval. Inhibition of striatal MOR+ neurons rescues fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These findings suggest that chronic opioid use induces GABAergic striatopallidal and striatonigral plasticity, leading to hypodopaminergic states and relapse.
Review
Pharmacology & Pharmacy
Lucia Caffino, Francesca Mottarlini, Gianmaria Zita, Dawid Gawlinski, Kinga Gawlinska, Karolina Wydra, Edmund Przegalinski, Fabio Fumagalli
Summary: Drug addiction is a devastating disorder that poses a huge economic and social burden on modern society, with adolescents being particularly vulnerable. Research has shown that exposure to cocaine during adolescence confers a vulnerable endophenotype primarily by inducing changes in neuroplasticity.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Beltran Alvarez-Perez, Herve Poras, Rafael Maldonado
Summary: Dual enkephalinase inhibitors (DENKIs) provide an innovative strategy to activate opioid receptors and treat opioid use disorders by protecting endogenous opioid peptides. They have the potential to be a safe and effective treatment for acute opioid withdrawal and a promising alternative to opioid substitution therapy with minimized side effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Psychology, Clinical
Victoria Rodriguez, Luis Alameda, Diego Quattrone, Giada Tripoli, Charlotte Gayer-Anderson, Edoardo Spinazzola, Giulia Trotta, Hannah E. Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Elena Bonora, Stephane Jamain, Jean-Paul Selten, Eva Velthorst, Lieuwe de Haan, Pierre-Michel Llorca, Manuel Arrojo, Julio Bobes, Miguel Bernardo, Celso Arango, James Kirkbride, Peter B. Jones, Bart P. Rutten, Alexander Richards, Pak C. Sham, Michael O'Donovan, Jim Van Os, Craig Morgan, Marta Di Forti, Robin M. Murray, Evangelos Vassos
Summary: This study suggests that combining polygenic risk scores (PRS) for severe psychiatric disorders with prediction models for psychosis phenotypes can improve discrimination ability and enhance our understanding of these phenotypes. PRS may have potential usefulness in specific populations such as those at high risk or in the early stages of psychosis.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Neurosciences
Clemence Simonnet, Manisha Sinha, Marie Goutierre, Imane Moutkine, Stephanie Daumas, Jean Christophe Poncer
Summary: The downregulation of KCC2 is associated with altered hippocampal rhythmogenesis and neuronal hyperexcitability, leading to deficits in spatial and contextual memory. Reduced KCC2 expression and function may disrupt GABA signaling and contribute to neurological and psychiatric disorders.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Francesco Petrelli, Tamara Zehnder, Anthony Laugeray, Sarah Mondoloni, Corrado Cali, Luca Pucci, Alicia Molinero Perez, Bianca Maria Bondiolotti, Eva De Oliveira Figueiredo, Glenn Dallerac, Nicole Deglon, Bruno Giros, Lorenzo Magrassi, Jean-Pierre Mothet, Manuel Mameli, Linda D. Simmler, Paola Bezzi
Summary: This study investigates the relationship between VMAT2 in astrocytes and the regulation of DA levels, finding that impairment of astrocytic control of DA leads to reduced DA levels, excessive grooming, and compulsive repetitive behaviors. The expression of VMAT2 in human PFC astrocytes validates the translational relevance of these findings.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Clinical Neurology
Chiara C. Bortolasci, Srisaiyini Kidnapillai, Briana Spolding, Trang T. T. Truong, Timothy Connor, Courtney Swinton, Bruna Panizzutti, Zoe S. J. Liu, Andrew Sanigorski, Olivia M. Dean, Tamsyn Crowley, Mark Richardson, Kiymet Bozaoglu, Katerina Vlahos, Stephanie Cowdery, Brad Watmuff, Stephan F. Steyn, De Wet Wolmarans, Barend J. Engelbrecht, Christina Perry, Katherine Drummond, Terence Pang, Stephane Jamain, Laura Gray, Sean L. McGee, Brian H. Harvey, Jee Hyun Kim, Marion Leboyer, Michael Berk, Ken Walder
Summary: The aim of this study was to identify a drug for repurposing in the treatment of bipolar depression. A gene expression signature was generated using human neuronal-like cells to represent the effects of drugs used to treat bipolar disorder. Trimetazidine was identified as a potential candidate for repurposing based on its similar transcriptional effects and its ability to increase ATP production.
Article
Biochemistry & Molecular Biology
Margaret Haney, Monique Vallee, Sandy Fabre, Stephanie Collins Reed, Marion Zanese, Ghislaine Campistron, Caroline A. Arout, Richard W. Foltin, Ziva D. Cooper, Tonisha Kearney-Ramos, Mathilde Metna, Zuzana Justinova, Charles Schindler, Etienne Hebert-Chatelain, Luigi Bellocchio, Adeline Cathala, Andrea Bari, Roman Serrat, David B. Finlay, Filippo Caraci, Bastien Redon, Elena Martin-Garcia, Arnau Busquets-Garcia, Isabelle Matias, Frances R. Levin, Francois-Xavier Felpin, Nicolas Simon, Daniela Cota, Umberto Spampinato, Rafael Maldonado, Yavin Shaham, Michelle Glass, Lars Lykke Thomsen, Helle Mengel, Giovanni Marsicano, Stephanie Monlezun, Jean-Michel Revest, Pier Vincenzo Piazza
Summary: Cannabis use disorder (CUD) is a widespread problem with no current pharmacological treatment options. AEF0117, a signaling-specific inhibitor of the cannabinoid receptor 1, has shown promise in reducing self-administration of cannabis and THC-related behavioral impairment without significant adverse effects in animal studies. Clinical trials involving healthy volunteers and individuals with CUD found that AEF0117 was safe, well tolerated, and significantly reduced the positive subjective effects of cannabis.
Article
Neurosciences
A. Garcia-Blanco, A. Ramirez-Lopez, F. Navarrete, M. S. Garcia-Gutierrez, J. Manzanares, E. Martin-Garcia, R. Maldonado
Summary: The endocannabinoid system plays a crucial role in behavioral responses in the central nervous system. The cannabinoid CB1 receptor is associated with loss of behavioral control during food addiction, while the CB2 receptor is linked to addictive-like behavior and drug addiction. In this study, the specific role of CB2R in food addiction was evaluated using an operant mouse model. It was found that the lack of CB2R provides protection against the development of food addiction and associated impulsive and depressive-like behavior, while overexpression of CB2R increases vulnerability to food addiction. Transcriptomic changes were also observed, providing mechanistic explanations for these behavioral changes. Therefore, CB2R may serve as a potential therapeutic target for regulating eating control and managing emotional effects in food addiction.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Psychology, Clinical
Filippo Corponi, Antoine Lefrere, Marion Leboyer, Frank Bellivier, Ophelia Godin, Josephine Loftus, Philippe Courtet, Caroline Dubertret, Emmanuel Haffen, Pierre Michel Llorca, Paul Roux, Mircea Polosan, Raymund Schwan, Ludovic Samalin, Emilie Olie, Bruno Etain, Fondamental Acad Centers Expertise Bipolar Disorder, Peggy Series, Raoul Belzeaux
Summary: This study investigates the relationship between different age cut-offs for early onset bipolar disorder (BD) and neurodevelopmental pathways. The results show that defining early onset as <=17 years best distinguishes neurodevelopmental patterns. These findings can improve patient stratification in future studies on BD pathophysiology and biomarkers.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Psychiatry
Lucia Sideli, Monica Aas, Diego Quattrone, Daniele La Barbera, Caterina La Cascia, Laura Ferraro, Luis Alameda, Eva Velthorst, Giulia Trotta, Giada Tripoli, Adriano Schimmenti, Andrea Fontana, Charlotte Gayer-Anderson, Simona Stilo, Fabio Seminerio, Crocettarachele Sartorio, Giovanna Marrazzo, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Domenico Berardi, Giuseppe D'Andrea, Celso Arango, Manuel Arrojo, Miguel Bernardo, Julio Bobes, Julio Sanjuan, Jose Luis Santos, Paulo Rossi Menezes, Cristina Marta Del-Ben, Hannah E. Jongsma, Peter B. Jones, James B. Kirkbride, Pierre-Michel Llorca, Andrea Tortell, Baptiste Pignon, Lieuwe de Haan, Jean-Paul Selten, Jim Van Os, Bart P. Rutten, Richard Bentall, Marta Di Fort, Robin M. Murray, Craig Morgan, Helen L. Fisher
Summary: This study aimed to investigate whether the relationship between childhood maltreatment and cognition in patients with psychosis and community controls was influenced by genetic factors related to psychosis. The study included first-episode psychosis patients (N=755) and unaffected controls (N=1219) from the EU-GEI study, who were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). The results showed that controlling for FH and SZ-PRS did not weaken the association between childhood maltreatment and IQ in either cases or controls, suggesting that genetic liability factors do not explain the lower levels of cognition in adults who experienced childhood maltreatment.
SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Maria del Mar Cajiao-Manrique, Rafael Maldonado, Elena Martin-Garcia
Summary: We have developed a mouse model of cannabinoid addiction using intravenous self-administration of WIN55,212-2. This model allows evaluation of addiction criteria including persistence of response, motivation for the drug, and compulsivity in the presence of punishment. It also measures parameters related to craving and predisposing factors. 35.6% of mice developed cannabinoid addiction criteria, allowing differentiation between resilient and vulnerable individuals. This model provides a reliable tool to study the neurobiological correlates of resilience and vulnerability to cannabinoid addiction.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Sara Memar, Eric Jiang, Vania F. Prado, Lisa M. Saksida, Timothy J. Bussey, Marco A. M. Prado
Summary: Open access to rodent cognitive data has been lagging behind other areas of neuroscience, but the use of touchscreen-automated cognitive testing in animal models provides standardized outputs that can be easily shared. These datasets can be combined with various neuro-technologies to analyze the relationship between neural activity and behavior. MouseBytes is a web-based repository that allows researchers to store, share, visualize, and analyze cognitive data, while MouseBytes+ integrates complementary neuro-technology data for multi-modal behavioral analysis.
Article
Psychiatry
Maria del Mar Cajiao-Manrique, Veronica Casado-Anguera, Alejandra Garcia-Blanco, Rafael Maldonado, Elena Martin-Garcia
Summary: This study investigates the development of cannabis addiction-like behavior in adult mice after adolescent exposure to THC. The results show that adolescent THC exposure does not affect the reinforcement of WIN 55,212-2 or the development of cannabis addiction-like behavior. However, THC pre-exposed mice display impulsive-like behavior in adulthood, especially in those that develop addiction-like criteria. Additionally, downregulated expression of drd2 and adora2a genes in NAc and HPC is observed in THC pre-exposed mice.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Jill Rocchetti, Caroline Fasano, Gregory Dal-Bo, Elisa Guma, Salah El Mestikawy, Tak-Pan Wong, Gohar Fakhfouri, Bruno Giros
Summary: Evidence suggests that excessive dopamine affects cognitive function in schizophrenia and antipsychotic drugs fail to improve cognitive deficits. Blocking D2 dopamine receptors leads to reshaping of mesohippocampal fibers, synaptic transmission deficits, and impairments in learning and memory. It is currently unknown how excessive dopamine affects hippocampal-related cognitive functions and the impact of antipsychotic drugs on hippocampal functions in this state.
Article
Multidisciplinary Sciences
Nuria Oliveras-Canellas, Anna Castells-Nobau, Lisset de la Vega-Correa, Jessica Latorre-Luque, Anna Motger-Alberti, Maria Arnoriaga-Rodriguez, Josep Garre-Olmo, Cristina Zapata-Tona, Claudia Coll-Martinez, Lluis Ramio-Torrenta, Jose Maria Moreno-Navarrete, Josep Puig, Francesc Villarroya, Rafel Ramos, Veronica Casado-Anguera, Elena Martin-Garcia, Rafael Maldonado, Jordi Mayneris-Perxachs, Jose Manuel Fernandez-Real
Summary: Obesity is linked to cognitive decline. We found 188 genes associated with cognitive performance in different domains through RNA sequencing of adipose tissue in three cohorts. These genes are mainly involved in synaptic function, phosphatidylinositol metabolism, the complement cascade, anti-inflammatory signaling, and vitamin metabolism. Targeted misexpression of candidate gene ortholog in the Drosophila fat body significantly affected memory and learning, suggesting potential therapeutic targets in adipose tissue.
Article
Genetics & Heredity
Ana Lokmer, Charanraj Goud Alladi, Rejane Troudet, Delphine Bacq-Daian, Anne Boland-Auge, Violaine Latapie, Jean-Francois Deleuze, Ravi Philip RajKumar, Deepak Gopal Shewade, Frank Belivier, Cynthia Marie-Claire, Stephane Jamain
Summary: The use of antipsychotic medication to treat schizophrenia is not always effective for all patients. Researchers have analyzed the blood DNA of patients and identified specific marks that could serve as biomarkers of antipsychotic response. Although specific predictive marks were not identified, valuable targets for future research have been identified.