Article
Neurosciences
Aqilah M. McCane, Meredyth A. Wegener, Mojdeh Faraji, Maria T. Rivera-Garcia, Kathryn G. Wallin-Miller, Vincent D. Costa, Bita Moghaddam
Summary: The study found that reward-guided associative learning in adolescent male rats is encoded differently by midbrain dopamine neurons in two different conditioning paradigms. Adolescent neurons show a muted reward response during operant conditioning but a significantly larger reward response during Pavlovian conditioning, indicating a different valuation of reward by adolescent neurons when it is not gated by action.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Immunology
Cassandra D. Gipson, Scott Rawls, Michael D. Scofield, Benjamin M. Siemsen, Emma O. Bondy, Erin E. Maher
Summary: Chronic drug use affects neuroimmune signaling and glutamatergic changes in the brain, highlighting a potential role for interactions between these systems in addiction processes and the development of pharmacotherapies for SUDs.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Behavioral Sciences
Poppy Watson, Justin Mahlberg
Summary: Environmental cues associated with rewarding outcomes play a significant role in addiction relapse. Previous studies have used the Pavlovian-to-instrumental transfer (PIT) task to investigate how cues influence ongoing instrumental responding, and found that stronger PIT effects are related to problematic alcohol use. However, it was unclear how these findings contribute to our understanding of addiction. In this study, researchers aimed to determine the associative mechanisms underlying the observed stimulus effects in the PIT task, and concluded that the task measures general effects rather than being sensitive to outcome devaluation.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Neurosciences
Sam Z. Bacharach, David A. Martin, Cassie A. Stapf, Fangmiao Sun, Yulong Li, Joseph F. Cheer, Donna J. Calu
Summary: This study reveals that CB1R signaling in the VTA regulates NAc dopamine levels to control sign-tracking behaviors. Inhibition of CB1R in the VTA decreases sign-tracking behaviors and increases NAc shell dopamine levels during reward delivery. These findings suggest that CB1R signaling in the VTA influences the balance between the conditioned stimulus-evoked and unconditioned stimulus-evoked dopamine responses in the NAc shell.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Megana Sundar, Devon Patel, Zachary Young, Kah-Chung Leong
Summary: Recent research suggests that oxytocin may reduce addictive behaviors by directly affecting the glutamatergic system, in addition to its established effects on dopamine. This new perspective provides insight into the potential use of oxytocin as a therapeutic target for addiction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Psychiatry
Akhil Sharma, Arman Harutyunyan, Bernard L. Schneider, Anna Moszczynska
Summary: The study found that rats overexpressing PARKIN gene have stronger self-administration ability for METH, while rats with PARKIN knockout are more prone to self-administer METH. This result provides useful models for studying the neural substrates underlying resilience or vulnerability to METH use disorder and identifies PARKIN as a novel potential drug target for treating heavy use of METH.
TRANSLATIONAL PSYCHIATRY
(2021)
Review
Pharmacology & Pharmacy
Johannes Petzold, Karen K. Szumlinski, Edythe D. London
Summary: Research suggests that modulation of the mGlu(5) receptor with allosteric modulators may offer a promising approach for ameliorating the devastating consequences of methamphetamine abuse. Further clinical research is needed to understand the mechanisms underlying these effects and develop tailored medications for Methamphetamine Use Disorder.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Neurosciences
Caroline Garceau, Anne-Noel Samaha, Thomas Cordahi, Alice Servonnet, Shaun Yon-Seng Khoo
Summary: Reward-associated cues can trigger incentive motivation for reward via Pavlovian-to-instrumental transfer, with glutamate signaling in the basolateral amygdala playing a role in modulating cue-triggered increases in motivation. The study showed that metabotropic group II glutamate receptors in the BLA mediate cue-triggered potentiation of incentive motivation for reward, suppressing both instrumental pursuit of the reward and anticipatory approach behavior.
PSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Caroline Garceau, Justine Marsault, Mike J. F. Robinson, Anne-Noel Samaha
Summary: Across both sexes, there are similar cue-triggered increases in reward seeking behaviors, and thirst satiation suppresses both water-seeking behavior and the anticipation of water reward. The activity of mGlu(2/3) receptors plays a regulatory role in cue-triggered increases in reward seeking.
PSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Cheng-Wei Lu, Chia-Chan Wu, Kuan-Ming Chiu, Ming-Yi Lee, Tzu-Yu Lin, Su-Jane Wang
Summary: Eupatilin can inhibit glutamate release from neuronal synaptosomes through various mechanisms and prevent excitotoxic damage in an animal model, indicating its potential therapeutic value.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Behavioral Sciences
L. M. Cope, A. Gheidi, M. E. Martz, E. R. Duval, H. Khalil, T. Allerton, J. D. Morrow
Summary: Cue-based associative learning is a fundamental component of animal behavior and may be related to addiction liability. Previous research has shown significant individual differences in this type of learning in non-human animals. This study revealed the existence of sign-trackers, goal-trackers, and intermediate responders in humans, with impulsivity being a significant predictor of sign-tracking behavior.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Davide Bassani, Matteo Pavan, Stephanie Federico, Giampiero Spalluto, Mattia Sturlese, Stefano Moro
Summary: This article provides an overview of the role of G protein-coupled receptors (GPCRs) in the onset and progression of amyotrophic lateral sclerosis (ALS), offering useful information and insights. This is of great importance for scientists worldwide in the fight against this disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Isabella Boccuni, Carlos Bas-Orth, Claus Bruehl, Andreas Draguhn, Richard Fairless
Summary: Glial glutamate transporters play an important role in neurotransmission and are regulated in various diseases. This study demonstrates that overexpression of GLAST can protect retinal ganglion cells from degeneration during inflammatory disease.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Bethania Mongi-Bragato, Maria Paula Avalos, Andrea S. Guzman, Constanza Garcia-Keller, Flavia A. Bollati, Liliana M. Cancela
Summary: This study investigated the role of endogenous enkephalin on adaptations in glutamate neurotransmission associated with repeated cocaine treatment using knockout proenkephalin mice. The results suggest a central role of enkephalin in regulating the glutamate mechanisms associated with cocaine sensitisation.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
M. Crespo, D. A. Leon-Navarro, M. Martin
Summary: Febrile seizures in children can lead to epilepsy in adults, with glutamate playing a key role in the development of neurological disorders. In the short term after seizures, GLT-1 levels increase and glutamate concentration decreases, while mGlu(5)R levels remain unchanged. However, in the long term, an increase in mGlu(5)R levels and decreases in GLT-1 and glutamate levels are observed, associated with the development of an anxious phenotype and potentially increased vulnerability to epileptic events in adults.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Review
Neurosciences
Christian Luscher, Trevor W. Robbins, Barry J. Everitt
NATURE REVIEWS NEUROSCIENCE
(2020)
Article
Neurosciences
D. M. Eagle, C. Schepisi, S. Chugh, S. Desai, S. Y. S. Han, T. Huang, J. J. Lee, C. Sobala, W. Ye, A. L. Milton, T. W. Robbins
PSYCHOPHARMACOLOGY
(2020)
Review
Behavioral Sciences
Zuzana Vaverkova, Amy L. Milton, Emiliano Mario
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2020)
Article
Pharmacology & Pharmacy
Ursule Taujanskaite, Emma N. Cahill, Amy L. Milton
Summary: Addiction can be viewed as a disorder of maladaptive learning and memory, with maladaptive drug memories serving as potential treatment targets for reconsolidation-blockade therapy. Different structures within the limbic corticostriatal system play varying roles in maladaptive drug memories, offering avenues for further research and potential therapeutic interventions.
CURRENT OPINION IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chiara Giuliano, Mickael Puaud, Rudolf N. Cardinal, David Belin, Barry J. Everitt
Summary: Excessive drinking is a key characteristic of alcohol addiction, but individuals addicted to alcohol also crave and seek alcohol despite negative consequences, eventually leading to intoxication. Habitual alcohol seeking behavior is associated with compulsive alcohol drinking, indicating the involvement of the habit system in the development of alcohol addiction.
Editorial Material
Neurosciences
Amy L. Milton
Summary: The concept of 'covert' memory reactivation in rats presents a potential breakthrough for disrupting maladaptive memories underlying PTSD, without the need for direct trauma exposure in patients. This finding offers promising implications for reconsolidation-based interventions in the translation to clinical practices.
NATURE NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Alexander C. W. Smith, Sietse Jonkman, Alexandra G. Difeliceantonio, Richard M. O'Connor, Soham Ghoshal, Michael F. Romano, Barry J. Everitt, Paul J. Kenny
Summary: The study showed that neural activity increases in the anterior dorsolateral striatum when mice successfully learn a new lever-press response, indicating that D1-MSNs encode new instrumental actions while D2-MSNs promote the expression of habitual actions. Disruption of D1-MSNs inhibits the consolidation process, whereas inhibition of D2-MSNs strengthens consolidation but blocks the expression of previously learned habit-like responses.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Federico Rotondo, Kathryn Biddle, John Chen, Josh Ferencik, Mathilde D'Esneval, Amy L. Milton
Summary: Despite the failure to replicate the effects of propranolol on fear memory reconsolidation, it is possible that the lack of memory destabilisation process engagement may have contributed to these results. Molecular correlates can be used to determine memory lability, which may provide further insight into the mechanism of memory disruption in reconsolidation.
Article
Behavioral Sciences
Lydia G. Rutherford, Amy L. Milton
Summary: This article discusses the challenges in developing treatment methods for mental health disorders and the benefits of using associative animal learning theory as a modeling approach. The article suggests that deconstructing complex mental health disorders into simple models and combining these models can reconstruct a more complex model. The article also highlights the translation and backtranslation of tasks between animal models and patients and its correlation with the concept of triangulation.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Veterinary Sciences
Indra A. Van Assche, Mc Stephen Padilla, Olivia S. R. P. Stupart, Amy L. Milton
Summary: This study demonstrates that the stress-enhanced fear learning procedure (SEFL) can be refined to produce PTSD-relevant behavioral and neurobiological changes in rats with reduced potential pain and suffering. Different variations of the procedure can generate different proportions of susceptible and resilient animals for future studies.
Article
Neurosciences
Katharina Zuhlsdorff, Laura Lopez-Cruz, Ethan G. Dutcher, Jolyon A. Jones, Claudia Pama, Stephen Sawiak, Shahid Khan, Amy L. Milton, Trevor W. Robbins, Edward T. Bullmore, Jeffrey W. Dalley
Summary: This study investigated the effects of early maternal separation on learning from positive and negative feedback and found that female rats exposed to early maternal separation displayed increased response 'stickiness' and reduced functional connectivity in specific brain regions after repeated adulthood stress. In contrast, control male rats exposed to the second stressor showed impaired learning from negative feedback and reduced functional connectivity. These findings suggest sex differences in response to early life adversity and subsequent stress.
NEUROBIOLOGY OF STRESS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Amy L. Milton
Summary: Mental health disorders affect a large part of the global population, and current treatments do not work for everyone. Understanding psychological and biological mechanisms is crucial for treatment development, and the use of translational animal models shows potential for transformative effects. This special issue, structured around the US National Institute of Mental Health's Research Domain Criteria approach, showcases reviews on how animal models can best be utilized to understand and treat the processes involved in mental health disorders.
EMERGING TOPICS IN LIFE SCIENCES
(2022)
Article
Neurosciences
Amy L. Milton, Ravi K. Das, Emiliano Merlo
Summary: The re-ignition of memory reconsolidation research sparked by Karim Nader in the early 2000s has led to excitement about developing interventions for mental health disorders. However, translating reconsolidation-based interventions to the clinic has been more challenging than expected. To address this challenge, it is suggested that understanding the interaction between prior expectations and information presented during memory reactivation sessions is important, and noninvasive biomarkers for memory destabilization should be identified.
BRAIN RESEARCH BULLETIN
(2023)
Review
Neurosciences
Uyen T. D. Bui, Amy L. Milton
Summary: Blocking memory reconsolidation can modify or weaken original memories, making it a potential treatment for mental health disorders. However, translating this treatment to the clinic faces challenges, with the greatest being overcoming the boundary conditions of the reconsolidation window. Despite some discrepant results and undefined limitations, studies have shown successful strategies to overcome these conditions and enable the clinical use of reconsolidation-based interventions.
Article
Psychiatry
Ethan G. Dutcher, Laura Lopez-Cruz, E. A. Claudia Pama, Mary-Ellen Lynall, Iris C. R. Bevers, Jolyon A. Jones, Shahid Khan, Stephen J. Sawiak, Amy L. Milton, Menna R. Clatworthy, Trevor W. Robbins, Edward T. Bullmore, Jeffrey W. Dalley
Summary: Early-life stress (ELS), particularly in the form of childhood neglect and abuse, has long-lasting effects on cognitive and neurobehavioral outcomes in rats. These effects interact with stress in adulthood and may be relevant for understanding the etiology of anxiety and depression in humans.
TRANSLATIONAL PSYCHIATRY
(2023)