scholarly journals CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Yong Li ◽  
Jimok Kim
Keyword(s):  
Working Memory ◽  
Motor Activity ◽  
Knockout Mice ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Spatial Working Memory ◽  
Fear Memory ◽  
Cb2 Receptor ◽  
Cb2 Receptors

Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas.

scholarly journals Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2126
Author(s):  
Battistina Asproni ◽  
Gabriele Murineddu ◽  
Paola Corona ◽  
Gérard A. Pinna
Keyword(s):  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Receptor Interaction ◽  
Pharmacological Properties ◽  
Cb2 Receptor ◽  
Antiemetic Effect ◽  
High Affinity ◽  
Cb1 Antagonist ◽  
Cb2 Receptors ◽  
Sar Study

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

scholarly journals Fine Spike Timing in Hippocampal–Prefrontal Ensembles Predicts Poor Encoding and Underlies Behavioral Performance in Healthy and Malformed Brains

2020 ◽  
Vol 31 (1) ◽  
pp. 147-158
Author(s):  
Amanda E Hernan ◽  
J Matthew Mahoney ◽  
Willie Curry ◽  
Seamus Mawe ◽  
Rod C Scott
Keyword(s):  
Working Memory ◽  
Spatial Information ◽  
Spatial Working Memory ◽  
Spike Timing ◽  
Functional Network ◽  
Long Term Memory ◽  
Encode Task ◽  
To Receive ◽  
Task Parameters

Abstract Spatial working memory (SWM) is a central cognitive process during which the hippocampus and prefrontal cortex (PFC) encode and maintain spatial information for subsequent decision-making. This occurs in the context of ongoing computations relating to spatial position, recall of long-term memory, attention, among many others. To establish how intermittently presented information is integrated with ongoing computations we recorded single units, simultaneously in hippocampus and PFC, in control rats and those with a brain malformation during performance of an SWM task. Neurons that encode intermittent task parameters are also well modulated in time and incorporated into a functional network across regions. Neurons from animals with cortical malformation are poorly modulated in time, less likely to encode task parameters, and less likely to be integrated into a functional network. Our results implicate a model in which ongoing oscillatory coordination among neurons in the hippocampal–PFC network describes a functional network that is poised to receive sensory inputs that are then integrated and multiplexed as working memory. The background temporal modulation is systematically altered in disease, but the relationship between these dynamics and behaviorally relevant firing is maintained, thereby providing potential targets for stimulation-based therapies.

scholarly journals A long-term cyclic plus tonic regimen of 17β-estradiol improves the ability to handle a high spatial working memory load in ovariectomized middle-aged female rats

2020 ◽  
Vol 118 ◽  
pp. 104656 ◽  
Author(s):  
Stephanie V. Koebele ◽  
Kenji J. Nishimura ◽  
Heather A. Bimonte-Nelson ◽  
Salma Kemmou ◽  
J. Bryce Ortiz ◽  
...  
Keyword(s):  
Working Memory ◽  
Spatial Working Memory ◽  
Memory Load ◽  
Female Rats ◽  
Middle Aged ◽  
Working Memory Load ◽  
17Β Estradiol

scholarly journals Bioactive Chemical Composition of Cannabis Extracts and Cannabinoid Receptors

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3466 ◽  
Author(s):  
Yi Yang ◽  
Rupali Vyawahare ◽  
Melissa Lewis-Bakker ◽  
Hance A. Clarke ◽  
Albert H. C. Wong ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Drug ◽  
Chemical Compositions ◽  
Least Squares Regression ◽  
Medical Cannabis ◽  
Cb2 Receptors ◽  
The Relationship

Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB1 and CB2 receptors. Using a partial least squares regression analysis, the chemical compositions of the extracts were then correlated to their corresponding cannabinoid receptor activities, thus generating predictive models that describe the receptor potency as a function of major phytocannabinoid content. Using the current dataset, meaningful models for CB1 and CB2 receptor agonism were obtained, and these reveal the insignificant relationships between the major phytocannabinoid content and receptor affinity for CB1 but good correlations between the two at CB2 receptors. These results also explain the anomalies between the receptor activities of pure phytocannabinoids and cannabis extracts. Furthermore, the models for CB1 and CB2 agonism in cannabis extracts predict the cannabinoid receptor activities of individual phytocannabinoids with reasonable accuracy. Here for the first time, we disclose a method to predict the relationship between the chemical composition, including phytocannabinoids, of cannabis extracts and cannabinoid receptor responses.

Modulation and Functional Involvement of CB2 Peripheral Cannabinoid Receptors During B-Cell Differentiation

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3605-3615 ◽  
Author(s):  
Pierre Carayon ◽  
Jean Marchand ◽  
Danielle Dussossoy ◽  
Jean-Marie Derocq ◽  
Omar Jbilo ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Receptor Antagonist ◽  
Cannabinoid Receptors ◽  
Receptor Subtype ◽  
B Cell Differentiation ◽  
Cb2 Receptor ◽  
Cb2 Receptors ◽  
B Cell Subsets

Two subtypes of G-protein–coupled cannabinoid receptors have been identified to date: the CB1 central receptor subtype, which is mainly expressed in the brain, and the CB2 peripheral receptor subtype, which appears particularly abundant in the immune system. We investigated the expression of CB2 receptors in leukocytes using anti-CB2 receptor immunopurified polyclonal antibodies. We showed that peripheral blood and tonsillar B cells were the leukocyte subsets expressing the highest amount of CB2 receptor proteins. Dual-color confocal microscopy performed on tonsillar tissues showed a marked expression of CB2 receptors in mantle zones of secondary follicles, whereas germinal centers (GC) were weakly stained, suggesting a modulation of this receptor during the differentiation stages from virgin B lymphocytes to memory B cells. Indeed, we showed a clear downregulation of CB2 receptor expression during B-cell differentiation both at transcript and protein levels. The lowest expression was observed in GC proliferating centroblasts. Furthermore, we investigated the effect of the cannabinoid agonist CP55,940 on the CD40-mediated proliferation of both virgin and GC B-cell subsets. We found that CP55,940 enhanced the proliferation of both subsets and that this enhancement was blocked by the CB2 receptor antagonist SR 144528 but not by the CB1 receptor antagonist SR 141716. Finally, we observed that CB2 receptors were dramatically upregulated in both B-cell subsets during the first 24 hours of CD40-mediated activation. These data strongly support an involvement of CB2 receptors during B-cell differentiation.

The Cannabinoid Agonist WIN55,212-2 Suppresses Opioid-induced Emesis in Ferrets

2001 ◽  
Vol 94 (5) ◽  
pp. 882-887 ◽  
Author(s):  
Isabelle I. Simoneau ◽  
Maged S. Hamza ◽  
Heriberto P. Mata ◽  
Erin M. Siegel ◽  
Todd W. Vanderah ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Cb1 Receptors ◽  
Cb2 Receptor ◽  
Selective Antagonist ◽  
Receptor Agonists ◽  
Antiemetic Activity ◽  
The Central Nervous System ◽  
Cannabinoid Agonist

Background Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. Methods Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg at the end of the experiments. All drugs were injected subcutaneously. WIN55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was administered 25 min before morphine. Retches and vomits were counted at 5-min intervals for 30 min after morphine injection. Results Retching and vomiting responses increased with increasing morphine doses up to 1.0 mg/kg, above which the responses decreased. Previous administration of naloxone prevented morphine-induced retching and vomiting. WIN55,212-2 dose-dependently reduced retching and vomiting. The ED50 was 0.05 mg/kg for retches and 0.03 mg/kg for vomits. At 0.13 mg/kg, retching decreased by 76% and vomiting by 92%. AM251, a CB1 receptor-selective antagonist, blocked the antiemetic actions of WIN55,212-2, but AM630, a CB2 receptor-selective antagonist, did not. Conclusions These results demonstrate that WIN55,212-2 prevents opioid-induced vomiting and suggest that the antiemetic activity of WIN55,212-2 occurs at CB1 receptors. This is consistent with findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated.

scholarly journals Dissociation in the Effects of Induced Neonatal Hypoxia-Ischemia on Rapid Auditory Processing and Spatial Working Memory in Male Rats

2015 ◽  
Vol 37 (4-5) ◽  
pp. 440-452 ◽  
Author(s):  
Amanda L. Smith ◽  
Michelle Alexander ◽  
James J. Chrobak ◽  
Ted S. Rosenkrantz ◽  
R. Holly Fitch
Keyword(s):  
Working Memory ◽  
Auditory Processing ◽  
Spatial Working Memory ◽  
Task Group ◽  
Hypoxia Ischemia ◽  
Group A ◽  
Group B ◽  
Anatomic Measures ◽  
Testing Group

Infants born prematurely are at risk for cardiovascular events causing hypoxia-ischemia (HI; reduced blood and oxygen to the brain). HI in turn can cause neuropathology, though patterns of damage are sometimes diffuse and often highly variable (with clinical heterogeneity further magnified by rapid development). As a result, though HI injury is associated with long-term behavioral and cognitive impairments in general, pathology indices for specific infants can provide only limited insight into individual prognosis. The current paper addresses this important clinical issue using a rat model that simulates unilateral HI in a late preterm infant coupled with long-term behavioral evaluation in two processing domains - auditory discrimination and spatial learning/memory. We examined the following: (1) whether deficits on one task would predict deficits on the other (suggesting that subjects with more severe injury perform worse across all cognitive domains) or (2) whether domain-specific outcomes among HI-injured subjects would be uncorrelated (suggesting differential damage to orthogonal neural systems). All animals (sham and HI) received initial auditory testing and were assigned to additional auditory testing (group A) or spatial maze testing (group B). This allowed within-task (group A) and between-task (group B) correlation. Anatomic measures of cortical, hippocampal and ventricular volume (indexing HI damage) were also obtained and correlated against behavioral measures. Results showed that auditory discrimination in the juvenile period was not correlated with spatial working memory in adulthood (group B) in either sham or HI rats. Conversely, early auditory processing performance for group A HI animals significantly predicted auditory deficits in adulthood (p = 0.05; no correlation in shams). Anatomic data also revealed significant relationships between the volumes of different brain areas within both HI and shams, but anatomic measures did not correlate with any behavioral measure in the HI group (though we saw a hippocampal/spatial correlation in shams, in the expected direction). Overall, current data provide an impetus to enhance tools for characterizing individual HI-related pathology in neonates, which could provide more accurate individual prognoses within specific cognitive/behavioral domains and thus improved patient-specific early interventions.

Sign in / Sign up

Export Citation Format

Share Document