Peripheral CB1 receptor blockade acts as a memory enhancer through a noradrenergic mechanism.

Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence.

Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons drives overconsumption of palatable food and obesity.

Palatable food can promote overfeeding beyond homeostatic requirements, thereby constituting a major risk to obesity. Here, the lack of cannabinoid type 1 receptor (CB1) in dorsal telencephalic glutamatergic neurons (Glu-CB1-KO) abrogated the overconsumption of palatable food and the development of obesity. On low-fat diet, no genotype differences were observed.

Cell type-specific genetic reconstitution of CB1 receptor subsets to assess their role in exploratory behaviour, sociability, and memory.

Several studies support the notion that exploratory behaviour depends on the functionality of the cannabinoid type 1 (CB1) receptor in a cell type-specific manner. Mice lacking the CB1 receptor in forebrain GABAergic or dorsal telencephalic glutamatergic neurons have served as essential tools revealing the necessary CB1 receptor functions in these two neuronal populations. However, whether these specific CB1 receptor populations are also sufficient within the endocannabinoid system for wild-type-like exploratory behaviour has remained unknown.

Differential glutamatergic and GABAergic contributions to the tetrad effects of Δ-tetrahydrocannabinol revealed by cell-type-specific reconstitution of the CB1 receptor.

Δ-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa, exerts its actions through the endocannabinoid system by stimulation of the cannabinoid type 1 (CB1) receptor. The widespread distribution of this receptor in different neuronal cell types and the plethora of functions that is modulated by the endocannabinoid system explain the versatility of the effects of THC. However, the cell types involved in the different THC effects are still not fully known.

Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration.

Background: Rapid-acting antidepressants ketamine and (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) have overcome some of the major limitations of classical antidepressants. However, little is known about sex-specific differences in the behavioral and molecular effects of ketamine and (2R,6R)-HNK in rodents.

Methods: We treated mice with an intraperitoneal injection of either saline, ketamine (30 mg kg) or (2R,6R)-HNK (10 mg kg).

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy.

Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]).

Addressing sufficiency of the CB1 receptor for endocannabinoid-mediated functions through conditional genetic rescue in forebrain GABAergic neurons.

Genetic inactivation of the cannabinoid CB1 receptor gene in different cell types in the brain has previously revealed necessary functions for distinct synaptic plasticity processes and behaviors. Here, we sought to identify CB1 receptor expression sites that are minimally required to reconstruct normal phenotypes. In a CB1-null background, we re-expressed endogenous CB1 receptors in forebrain GABAergic neurons, thereby assessing the sufficiency of CB1 receptors.

ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation.

Huntington's disease (HD) is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor). By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach.

Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation.

Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown.

Impaired 2-AG Signaling in Hippocampal Glutamatergic Neurons: Aggravation of Anxiety-Like Behavior and Unaltered Seizure Susceptibility.

Background: Postsynaptically generated 2-arachidonoylglycerol activates the presynaptic cannabinoid type-1 receptor, which is involved in synaptic plasticity at both glutamatergic and GABAergic synapses. However, the differential function of 2-arachidonoylglycerol signaling at glutamatergic vs GABAergic synapses in the context of animal behavior has not been investigated yet.

Methods: Here, we analyzed the role of 2-arachidonoylglycerol signaling selectively in hippocampal glutamatergic neurons.