scholarly journals The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation

2021 ◽  
Vol 15 ◽  
Author(s):  
Liangpei Chen ◽  
He Yan ◽  
Yufang Wang ◽  
Ziping He ◽  
Qihao Leng ◽  
...  
Keyword(s):  
Boundary Conditions ◽  
Relapse Prevention ◽  
Therapeutic Potential ◽  
Brain Structures ◽  
Vital Role ◽  
Memory Reconsolidation ◽  
Molecular Processes ◽  
Memory Engram ◽  
The Brain ◽  
Drug Relapse

Drug addiction can be seen as a disorder of maladaptive learning characterized by relapse. Therefore, disrupting drug-related memories could be an approach to improving therapies for addiction. Pioneering studies over the last two decades have revealed that consolidated memories are not static, but can be reconsolidated after retrieval, thereby providing candidate pathways for the treatment of addiction. The limbic–corticostriatal system is known to play a vital role in encoding the drug memory engram. Specific structures within this system contribute differently to the process of memory reconsolidation, making it a potential target for preventing relapse. In addition, as molecular processes are also active during memory reconsolidation, amnestic agents can be used to attenuate drug memory. In this review, we focus primarily on the brain structures involved in storing the drug memory engram, as well as the molecular processes involved in drug memory reconsolidation. Notably, we describe reports regarding boundary conditions constraining the therapeutic potential of memory reconsolidation. Furthermore, we discuss the principles that could be employed to modify stored memories. Finally, we emphasize the challenge of reconsolidation-based strategies, but end with an optimistic view on the development of reconsolidation theory for drug relapse prevention.

scholarly journals Gene Set Enrichment Analysis (GSEA) of Upregulated Genes in Cocaine Addiction Reveals miRNAs as Potential Therapeutic Agents

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Enrichment Analysis ◽  
Vital Role ◽  
Cocaine Addiction ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Upregulated Genes ◽  
The Brain

Cocaine addiction is a global health problem that causes substantial damage to the health of addicted individuals around the world. Dopamine synthesizing neurons in the brain play a vital role in the addiction to cocaine. But the underlying molecular mechanisms that help cocaine exert its addictive effect have not been very well understood. Bioinformatics can be a useful tool in the attempt to broaden our understanding in this area. In the present study, Gene Set Enrichment Analysis (GSEA) was carried out on the upregulated genes from a dataset of Dopamine synthesizing neurons of post-mortem human brain of cocaine addicts. As a result of this analysis, 3 miRNAs have been identified as having significant influence on transcription of the upregulated genes. These 3 miRNAs hold therapeutic potential for the treatment of cocaine addiction.

scholarly journals Gene Set Enrichment Analysis (GSEA) of Upregulated Genes in Cocaine Addiction Reveals miRNAs as Potential Therapeutic Agents

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Enrichment Analysis ◽  
Vital Role ◽  
Cocaine Addiction ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Upregulated Genes ◽  
The Brain

<p>Cocaine addiction is a global health problem that causes substantial damage to the health of addicted individuals around the world. Dopamine synthesizing neurons in the brain play a vital role in the addiction to cocaine. But the underlying molecular mechanisms that help cocaine exert its addictive effect have not been very well understood. Bioinformatics can be a useful tool in the attempt to broaden our understanding in this area. In the present study, Gene Set Enrichment Analysis (GSEA) was carried out on the upregulated genes from a dataset of Dopamine synthesizing neurons of post-mortem human brain of cocaine addicts. As a result of this analysis, 3 miRNAs have been identified as having significant influence on transcription of the upregulated genes. These 3 miRNAs hold therapeutic potential for the treatment of cocaine addiction. </p>

scholarly journals Targeting the Reconsolidation of Licit Drug Memories to Prevent Relapse: Focus on Alcohol and Nicotine

2021 ◽  
Author(s):  
Segev Barak ◽  
Koral Goltseker
Keyword(s):  
Animal Models ◽  
Boundary Conditions ◽  
Tobacco Smoking ◽  
Alcohol Drinking ◽  
Relapse Prevention ◽  
Memory Reconsolidation ◽  
Clinical Challenge ◽  
Prevention Therapy ◽  
Growing Body ◽  
Legal Substances

Alcohol and nicotine are widely-abused legal substances worldwide. Relapse to alcohol or tobacco seeking and consumption after abstinence is a major clinical challenge, and is often evoked by cue-induced craving. Therefore, disruption of the memory for the cue-drug association is expected to suppress relapse. Memories have been postulated to become labile shortly after their retrieval, during a &ldquo;memory reconsolidation&rdquo; process. Interference with the reconsolidation of drug-associated memories has been suggested as a possible strategy to reduce or even prevent cue-induced craving and relapse. Here, we surveyed the growing body of studies in animal models and in humans assessing the effectiveness of pharmacological or behavioral manipulations in reducing relapse by interfering with the reconsolidation of alcohol and nicotine/tobacco memories. Our review points to the potential of targeting the reconsolidation of these memories as a strategy to suppress relapse to alcohol drinking and tobacco smoking. However, we discuss several critical limitations and boundary conditions, which should be considered to improve the consistency and replicability in the field, and for development of an efficient reconsolidation-based relapse prevention therapy.

scholarly journals Gene Set Enrichment Analysis (GSEA) of Upregulated Genes in Cocaine Addiction Reveals miRNAs as Potential Therapeutic Agents

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Enrichment Analysis ◽  
Vital Role ◽  
Cocaine Addiction ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Upregulated Genes ◽  
The Brain

AbstractCocaine addiction is a global health problem that causes substantial damage to the health of addicted individuals around the world. Dopamine synthesizing neurons in the brain play a vital role in the addiction to cocaine. But the underlying molecular mechanisms that help cocaine exert its addictive effect have not been very well understood. Bioinformatics can be a useful tool in the attempt to broaden our understanding in this area. In the present study, Gene Set Enrichment Analysis (GSEA) was carried out on the upregulated genes from a dataset of Dopamine synthesizing neurons of post-mortem human brain of cocaine addicts. As a result of this analysis, 3 miRNAs have been identified as having significant influence on transcription of the upregulated genes. These 3 miRNAs hold therapeutic potential for the treatment of cocaine addiction.

scholarly journals Noradrenergic projections from the locus coeruleus to the amygdala constrain auditory fear memory reconsolidation

2020 ◽  
Author(s):  
Josue Haubrich ◽  
Matteo Bernabo ◽  
Karim Nader
Keyword(s):  
Boundary Condition ◽  
Boundary Conditions ◽  
Locus Coeruleus ◽  
Molecular Mechanisms ◽  
Fear Memory ◽  
Memory Formation ◽  
Memory Reconsolidation ◽  
Memory Encoding ◽  
Memory Strength ◽  
The Brain

ABSTRACTMemory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we extend the understanding of the mechanisms implicated in reconsolidation-resistant memories by investigating the hypothesis that specific modulatory signals shape memory formation into a state that lacks lability. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on reconsolidation is set at the time of encoding by the action of the NOR-LC.

scholarly journals Gene Set Enrichment Analysis (GSEA) of Upregulated Genes in Cocaine Addiction Reveals miRNAs as Potential Therapeutic Agents

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Enrichment Analysis ◽  
Vital Role ◽  
Cocaine Addiction ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Upregulated Genes ◽  
The Brain

<p>Cocaine addiction is a global health problem that causes substantial damage to the health of addicted individuals around the world. Dopamine synthesizing neurons in the brain play a vital role in the addiction to cocaine. But the underlying molecular mechanisms that help cocaine exert its addictive effect have not been very well understood. Bioinformatics can be a useful tool in the attempt to broaden our understanding in this area. In the present study, Gene Set Enrichment Analysis (GSEA) was carried out on the upregulated genes from a dataset of Dopamine synthesizing neurons of post-mortem human brain of cocaine addicts. As a result of this analysis, 3 miRNAs have been identified as having significant influence on transcription of the upregulated genes. These 3 miRNAs hold therapeutic potential for the treatment of cocaine addiction. </p>

scholarly journals Noradrenergic projections from the locus coeruleus to the amygdala constrain fear memory reconsolidation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Josué Haubrich ◽  
Matteo Bernabo ◽  
Karim Nader
Keyword(s):  
Boundary Condition ◽  
Boundary Conditions ◽  
Locus Coeruleus ◽  
Molecular Mechanisms ◽  
Fear Memory ◽  
Memory Formation ◽  
Memory Reconsolidation ◽  
Memory Encoding ◽  
Memory Strength ◽  
The Brain

Memory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we investigated the hypothesis that specific modulatory signals shape memory formation into a state that is reconsolidation-resistant. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala of rats. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on reconsolidation is set at the time of encoding by the action of the NOR-LC.

scholarly journals Targeting the Reconsolidation of Licit Drug Memories to Prevent Relapse: Focus on Alcohol and Nicotine

2021 ◽  
Vol 22 (8) ◽  
pp. 4090
Author(s):  
Segev Barak ◽  
Koral Goltseker
Keyword(s):  
Animal Models ◽  
Boundary Conditions ◽  
Tobacco Smoking ◽  
Alcohol Drinking ◽  
Relapse Prevention ◽  
Memory Reconsolidation ◽  
Clinical Challenge ◽  
Prevention Therapy ◽  
Growing Body ◽  
Legal Substances

Alcohol and nicotine are widely abused legal substances worldwide. Relapse to alcohol or tobacco seeking and consumption after abstinence is a major clinical challenge, and is often evoked by cue-induced craving. Therefore, disruption of the memory for the cue–drug association is expected to suppress relapse. Memories have been postulated to become labile shortly after their retrieval, during a “memory reconsolidation” process. Interference with the reconsolidation of drug-associated memories has been suggested as a possible strategy to reduce or even prevent cue-induced craving and relapse. Here, we surveyed the growing body of studies in animal models and in humans assessing the effectiveness of pharmacological or behavioral manipulations in reducing relapse by interfering with the reconsolidation of alcohol and nicotine/tobacco memories. Our review points to the potential of targeting the reconsolidation of these memories as a strategy to suppress relapse to alcohol drinking and tobacco smoking. However, we discuss several critical limitations and boundary conditions, which should be considered to improve the consistency and replicability in the field, and for development of an efficient reconsolidation-based relapse-prevention therapy.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

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