Article
Neurosciences
Adam Gordon-Fennell, Garret D. Stuber
Summary: Studies have revealed generalizable findings across molecularly defined cell types in areas of the basal forebrain and anterior hypothalamus. Optogenetic stimulation of GABAergic neurons in these brain regions drives reward, while optogenetic stimulation of glutamatergic neurons in these regions drives aversion.
Article
Neurosciences
Roni Hogri, Hannah Luise Teuchmann, Bernhard Heinke, Raphael Holzinger, Lidia Trofimova, Juergen Sandkuehler
Summary: The neuronal signaling pathways underlying pain and emotion regulation by neurons in the central nucleus of the amygdala (CeA) are not fully understood. This study shows that CeA neurons expressing the CaMKIIa gene project to the lateral parabrachial nucleus (LPBN) and inhibit LPBN neurons' responses to pain and aversive stimuli. Optogenetic stimulation of CeA-LPBN projections in rats reduces nocifensive responses and promotes positive behaviors. This finding suggests the potential use of this pathway in promoting pain resilience and recovery in clinical settings.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Ping Cai, Wei-Kun Su, Jin-Sheng Zhang, Pei-Chang Liu, Feng Liu, Ren-Fu Liu, Zhang-Shu Li, Zhong-Hua Zhu, Wen-Hao Xiao, Yong-Huai Hu, Hong-Da Cai, Xiao-Dan Wu, Liang-Cheng Zhang, Changxi Yu, Li Chen
Summary: Recent evidence suggests a potential overlap between general anesthesia and sleep-wake behavior. In this study, using fiber photometry, it was observed that the activity of GABAergic neurons in the basal forebrain (BF) was inhibited during isoflurane anesthesia, but gradually restored during emergence. Activation of these neurons reduced sensitivity to isoflurane, delayed induction, and accelerated emergence from anesthesia. Photostimulation of GABAergic terminals in the thalamic reticular nucleus (TRN) also promoted cortical activation and behavioral emergence from anesthesia.
JOURNAL OF NEUROSCIENCE
(2023)
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.
Article
Endocrinology & Metabolism
D. M. Pfabigan, M. Ruetgen, S. L. Kroll, I Riecansky, C. Lamm
Summary: This study investigated the impact of acute opioid administration on error processing. Participants who received opioids showed decreased Pe amplitudes and frontal delta oscillations, indicating a general reduction in error processing. The effects of opioids were evident in more elaborate stages of error processing, influencing conscious error appraisal and evidence accumulation processes.
PSYCHONEUROENDOCRINOLOGY
(2021)
Article
Neurosciences
Hannah N. Carlson, Brooke A. Christensen, Wayne E. Pratt
Summary: This study suggests that the lateral habenula may not be the key factor in increasing feeding behavior, but rather stimulating μ-opioid receptors leads to a decrease in consumption of highly palatable food and an increase in intake of standard chow, highlighting a differential role for the lateral habenula in regulating hedonic consummatory behavior.
NEUROSCIENCE LETTERS
(2022)
Article
Neurosciences
Megan K. Gautier, Christy M. Kelley, Sang Han Lee, Melissa J. Alldred, John Mcdaid, Elliott J. Mufson, Grace E. Stutzmann, Stephen D. Ginsberg
Summary: Down syndrome (DS), a genetic disorder, affects brain development and cognitive abilities. Maternal choline supplementation shows potential for protecting vulnerable neurons and improving cognitive function.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Jens Devoght, Joris Comhair, Giovanni Morelli, Jean-Michel Rigo, Rudi D'Hooge, Chadi Touma, Rupert Palme, Ilse Dewachter, Martin Vandeven, Robert J. Harvey, Serge N. Schiffmann, Elisabeth Piccart, Bert Brone
Summary: In this study, the role of GlyR alpha 2 in dopamine-stimulated striatal cell activity and behavior was investigated. It was shown that depletion of GlyR alpha 2 enhances dopamine-induced increases in the activity of putative dopamine D1 receptor-expressing striatal projection neurons, but does not alter midbrain dopamine neuron activity. Furthermore, locomotor response to d-amphetamine was enhanced in GlyR alpha 2 knockout animals, and this increase correlated with c-fos expression in the dorsal striatum. 3-D modeling revealed an increase in the neuronal ensemble size in the striatum in response to D-amphetamine in GlyR alpha 2 KO mice. Finally, enhanced appetitive conditioning was observed in GlyR alpha 2 KO animals, likely due to increased motivation rather than changes in associative learning or hedonic response. Overall, this study demonstrates that GlyR alpha 2 is an important regulator of dopamine-stimulated striatal activity and function.
Article
Neurosciences
Pedro Trevizan-Bau, Rishi R. Dhingra, Werner I. Furuya, Davor Stanic, Stuart B. Mazzone, Mathias Dutschmann
Summary: Eupnea is generated by neural circuits in the ponto-medullary brainstem and modulated by higher brain inputs for voluntary control of breathing and orofacial behaviors. Descending inputs from cortical areas predominantly target the PAG and KFn, suggesting specific relay of volitional motor commands for vocalization and coordination of breathing with other orofacial behaviors. Additionally, limbic or autonomic systems connect to broadly distributed downstream bulbar respiratory networks.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Review
Behavioral Sciences
C. Sandoval-Caballero, L. Luarte, Y. Jimenez, C. Jaque, F. Cifuentes, G. A. Arenas, M. Figueroa, J. Jara, P. K. Olszewski, J. A. Teske, C. E. Perez-Leighton
Summary: This study conducted a systematic search and meta-analysis of rodent dose-response studies to evaluate the effects of opioid receptor (OR) agonists and antagonists on feeding behaviors and food intake. The results showed overall orexigenic effects of central MOR agonists and anorexigenic effects of OR antagonists. Additionally, peripheral OR agonists selectively increased the intake of fat-preferred foods, while not affecting the intake of sweet carbohydrate-preferred foods. These findings suggest that OR regulation of intake, motivation, and choice is influenced by food macronutrient composition.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Neurosciences
Julie Bailly, Florence Allain, Eric Schwartz, Chloe Tirel, Charles Dupuy, Florence Petit, Marco A. Diana, Emmanuel Darcq, Brigitte L. Kieffer
Summary: This study found that the mu opioid receptor in the brain can promote aversive emotional states, and it is controlled by two different neural pathways (Hb-MOR/interpeduncular nucleus and Hb-MOR/dorsal raphe nucleus) that regulate despair and anxiety, respectively. These findings are important for understanding emotional balance and addiction mechanisms.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Chemistry, Medicinal
Ann M. Decker, Md Toufiqur Rahman, Chad M. Kormos, David Hesk, Emmanuel Darcq, Brigitte L. Kieffer, Chunyang Jin
Summary: This study synthesized and characterized the first GPR88 radio-ligand, [3H]RTI-33, derived from a synthetic agonist RTI-13951-33. [3H]RTI-33 showed specific and saturable binding (KD of 85 nM) in membranes prepared from stable PPLS-HA-hGPR88-CHO cells, and a competition binding assay was developed to determine binding affinities of several known GPR88 agonists. This radioligand represents a powerful tool for future mechanistic and cell-based ligand-receptor interaction studies of GPR88.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemical Research Methods
Maria del Mar Muniz Moreno, Claire Gaveriaux-Ruff, Yann Herault
Summary: Gdaphen is a fast joint-pipeline that allows for the identification of important predictor variables in phenotypic data. It provides statistical analysis and visualization options to support the conclusions of the analysis. Gdaphen simplifies the analysis process for medical or preclinical behavioral researchers.
BMC BIOINFORMATICS
(2023)
Article
Neurosciences
Emmanuel Darcq, Dominique Nouel, Giovanni Hernandez, Matthew Pokinko, Polina Ash, Luc Moquin, Alain Gratton, Brigitte Kieffer, Cecilia Flores
Summary: The protective effects of Dcc haploinsufficiency against the rewarding effects of stimulant drugs do not extend to opioids and ethanol, suggesting different brain circuits mediate the rewarding effects of these substances.
PSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Lola Welsch, Esther Colantonio, Mathilde Frison, Desiree A. Johnson, Shannan P. Mcclain, Victor Mathis, Matthew R. Banghart, Sami Ben Hamida, Emmanuel Darcq, Brigitte L. Kieffer
Summary: This study found that μ opioid receptor neurons in the dorsal raphe nucleus (DRN) participate in reward and emotional responses. These neurons respond to rewarding stimuli and their optoactivation has reinforcing effects and promotes positive emotional responses. Furthermore, their effects are partially mediated by their projections to the lateral hypothalamus.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Chemistry, Medicinal
Md Toufiqur Rahman, Ann M. Decker, Sami Ben Hamida, David A. Perrey, Hetti Handi Chaminda Lakmal, Rangan Maitra, Emmanuel Darcq, Brigitte L. Kieffer, Chunyang Jin
Summary: We reported a new GPR88 agonist, RTI-122, with high potency and good metabolic stability, which could improve alcohol drinking behavior. This suggests that RTI-122 may serve as a promising lead compound for GPR88 agonist drug discovery research.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
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.
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
Psychiatry
Florence Allain, Aliza T. Ehrlich, Michael McNicholas, Florence Gross, Weiya Ma, Brigitte L. Kieffer, Emmanuel Darcq
Summary: This study found that the antidepressant tianeptine mainly exerts its effects on the brain through the μ-opioid receptor, and it exhibits analgesic, locomotor, and rewarding behaviors in animal models. These effects can only be observed in mice with positive expression of the opioid receptor, and are ineffective in mice with negative expression. In addition, chronic use of tianeptine may lead to tolerance to its analgesic and hyperlocomotor effects.
FRONTIERS IN PSYCHIATRY
(2023)
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
Neurosciences
Dersu Ozdemir, Florence Allain, Brigitte L. Kieffer, Emmanuel Darcq
Summary: Opioid use disorder is a chronic brain disease caused by long-term neuroadaptations resulting from repeated opioid consumption and withdrawal. These neuroadaptations lead to negative affect and various symptoms, such as loss of motivation, anxiety, social deficits, heightened stress reactivity, emotional and physical pain, dysphoria, sleep disorders, and chronic irritability. Understanding the neurocircuitry involved in withdrawal and abstinence is crucial for treatment and relapse prevention.
Article
Neurosciences
Gabriel Araujo Costa, Nivea Karla de Gusmao Taveiros Silva, Priscila Marianno, Priti Chivers, Alexis Bailey, Rosana Camarini
Summary: Environmental enrichment (EE) can modulate the expression and epigenetic regulation of BDNF through altering the methylation level of BDNF exon IV, resulting in upregulation of BDNF exons II, IV, VI, and IX. However, this regulation does not have a significant impact on anxiety-like behavior and stress levels in mice exposed to EE.
Article
Neurosciences
Lola Welsch, Esther Colantonio, Camille Falconnier, Cedric Champagnol-DiLiberti, Florence Allain, Sami Ben Hamida, Emmanuel Darcq, Pierre-Eric Lutz, Brigitte L. Kieffer
Summary: Chronic morphine abstinence leads to reduced MOR function in DRN-MOR neurons and abnormal self-stimulation, which may increase propensity for addiction-related behaviors.
BIOLOGICAL PSYCHIATRY
(2023)
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)