112,079 research outputs found
Toward understanding the neurobiology of social attachment: role of estrogen receptors in the medial amygdala
No full text[No abstract available
Unidirectional opioid-cannabinoid cross-tolerance in the modulation of social play behavior in rats.
No full textRationale: The endocannabinoid and the endogenous opioid systems interact in the modulation of social play behavior, a highly rewarding social activity abundantly expressed in young mammals. Prolonged exposure to opioid or cannabinoid receptor agonists induces cross-tolerance or cross-sensitization to their acute behavioral effects. Objectives and methods: Behavioral and biochemical experiments were performed to investigate whether cross-tolerance or cross-sensitization occurs to the play-enhancing effects of cannabinoid and opioid drugs on social play behavior, and the possible brain substrate involved. Results: The play-enhancing effects induced by systemic administration of JZL184, which inhibits the hydrolysis of the endocannabinoid 2-AG, were suppressed in animals repeatedly pretreated with the opioid receptor agonist morphine. Conversely, acute morphine administration increased social play in rats pretreated with vehicle or with either JZL184 or the cannabinoid agonist WIN55,212-2. Acute administration of JZL184 increased the activation of both CB1 receptors and their effector Akt in the nucleus accumbens and prefrontal cortex, brain regions important for the expression of social play. These effects were absent in animals pretreated with morphine. Furthermore, only animals repeatedly treated with morphine and acutely administered with JZL184 showed reduced activation of CB1 receptors and Akt in the amygdala. Conclusions: The present study demonstrates a dynamic opioid–cannabinoid interaction in the modulation of social play behavior, occurring in limbic brain areas strongly implicated in social play behavior. A better understanding of opioid–cannabinoid interactions in social play contributes to clarify neurobiological aspects of social behavior at young age, which may provide new therapeutic targets for social dysfunctions
Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping
No full textThe endocannabinoid system (ECS) critically regulates stress responsivity and emotional behavior throughout development. It regulates anxiety-like behaviors in humans and animal models. In addition, it is sensitive to early life stress at the gene expression level in a sex-dependent and region-dependent manner, and these changes are already evident in the adolescent brain. The ECS modulates the neuroendocrine and behavioral effects of stress, and is also capable of being affected by stress exposure itself. Early life stress interferes with the development of corticolimbic circuits, a major location of endocannabinoid receptors, and increases vulnerability to adult psychopathology. Early life stress alters the ontogeny of the ECS, resulting in a sustained deficit in its function, particularly within the hippocampus. Specifically, exposure to early stress results in bidirectional changes in anandamide and 2-AG tissue levels within the amygdala and hippocampus and reduces hippocampal endocannabinoid function at puberty. CB1 receptor densities across all brain regions are downregulated later in life following exposure to early life stress. Manipulations affecting the glucocorticoid and the endocannabinoid systems persistently adjust individual emotional responses and synaptic plasticity. This review aims to show the bidirectional trajectories of endocannabinoid modulation of emotionality in reaction to early life stress
Study of expression and role of Metabotropic Glutamate Receptors in Human Acute Myeloid Leukemia cell lines and involvement of L1-CAM in migration of mGluR1+ mouse melanoma cell lines
No full textmGluRs are a family of G-coupled protein receptors with widespread expression in the central nervous system (CNS), some normal tissues, and in various cancers. The predominant functions of mGluRs in the CNS are modulating presynaptic neurotransmission but in cancers, mGluRs are involved in regulating cell proliferation.
Acute Myeloid Leukemia (AML) is a clonal, malignant disease of hematopoietic tissue and is the most common type of acute leukemia in adults and the elderly. Despite the wide number of drugs available to treat this disease, there are many unmet needs in AML therapy; relapsed or refractory patients or those unable to receive intensive chemotherapy display a poor prognosis.
Skin cancer is described as the abnormal multiplication of skin cells, which is frequently detected in sun-exposed regions. Basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, cutaneous lymphoma, Kaposi sarcoma, and melanoma are the six primary forms. Melanoma is the most severe form of skin cancer and is caused by melanocyte transformation. In the United States, invasive melanoma is expected to account for about 100,000 new cases and over 7,000 fatalities from skin cancer in 2022.
In this study, there are two distinct studies, in one, we evaluated metabotropic glutamate receptors (mGluRs) to assess if one or more of mGluRs may be a putative therapeutic target in AML. We have found a novel, previously unknown role of mGluRs in AML. The second study is to use mGluR1+ mouse melanoma cell lines to determine if the presence of L1-NCAM (CD171), a neural cell adhesion molecule 1 is involved in cell migration as shown previously in glioblastoma cell
A preclinical model of Post-Traumatic Stress Disorder (PTSD) capturing both the emotional and cognitive features of the disease: behavioral validation
No full textDEVELOPMENTAL EXPOSURE TO CANNABINOIDS CAUSES SUBTLE AND ENDURING NEUROFUNCTIONAL ALTERATIONS
No full textCannabis sativa preparations are among the illicit drugs most commonly used by pregnant women in Western countries. Although they are often considered relatively harmless, increasing evidence Suggests that developmental exposure to cannabinoids induces subtle microfunctional alterations in the offspring. In the present review, we summarize human and animal evidence examining the behavioral and neurobiological effects of exposure to cannabinoids during pregnancy and lactation. These studies show that the endocannabinoid system plays a crucial role in the ontogeny of the central nervous system and its activation, during brain development, can induce subtle and long-lasting neurofunctional alterations
Role of Nuclear Imaging to Understand the Neural Substrates of Brain Disorders in Laboratory Animals: Current Status and Future Prospects
No full textMolecular imaging, which allows the real-time visualization, characterization and measurement of biological processes, is becoming increasingly used in neuroscience research. Scintigraphy techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provide qualitative and quantitative measurement of brain activity in both physiological and pathological states. Laboratory animals, and rodents in particular, are essential in neuroscience research, providing plenty of models of brain disorders. The development of innovative high-resolution small animal imaging systems together with their radiotracers pave the way to the study of brain functioning and neurotransmitter release during behavioral tasks in rodents. The assessment of local changes in the release of neurotransmitters associated with the performance of a given behavioral task is a turning point for the development of new potential drugs for psychiatric and neurological disorders. This review addresses the role of SPECT and PET small animal imaging systems for a better understanding of brain functioning in health and disease states. Brain imaging in rodent models faces a series of challenges since it acts within the boundaries of current imaging in terms of sensitivity and spatial resolution. Several topics are discussed, including technical considerations regarding the strengths and weaknesses of both technologies. Moreover, the application of some of the radioligands developed for small animal nuclear imaging studies is discussed. Then, we examine the changes in metabolic and neurotransmitter activity in various brain areas during task-induced neural activation with special regard to the imaging of opioid, dopaminergic and cannabinoid receptors. Finally, we discuss the current status providing future perspectives on the most innovative imaging techniques in small laboratory animals. The challenges and solutions discussed here might be useful to better understand brain functioning allowing the translation of preclinical results into clinical applications
Cannabis and the developing brain: insights from behavior.
No full textThe isolation and identification, in 1964, of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, opened the door to a whole new field of medical research. The exploration of the therapeutic potential of THC and other natural and synthetic cannabinoid compounds was paralleled by the discovery of the endocannabinoid system, comprising cannabinoid receptors and their endogenous ligands, which offered exciting new insights into brain function. Besides its well-known involvement in specific brain functions, such as control of movement, memory and emotions, the endocannabinoid system plays an important role in fundamental developmental processes such as cell proliferation, migration and differentiation. For this reason, changes in its activity during stages of high neuronal plasticity, such as the perinatal and the adolescent period, can have long-lasting neurobehavioral consequences. Here, we summarize human and animal studies examining the behavioral and neurobiological effects of in utero and adolescent exposure to cannabis. Since cannabis preparations are widely used and abused by young people, including pregnant women, understanding how cannabinoid compounds affect the developing brain, leading to neurobehavioral alterations or neuropsychiatric disorders later in life, is a serious health issue. In addition, since the endocannabinoid system is emerging as a novel therapeutic target for the treatment of several neuropsychiatric diseases, a detailed investigation of possible adverse effects of cannabinoid compounds on the central nervous system (CNS) of immature individuals is warranted. © 2008 Elsevier B.V. All rights reserved
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