Topic: CB1 receptor

A cognitive model of stress posits that psycho-affective disorders can arise from a perceived lack of stress control. Uncontrollability is linked to perturbed prefrontocortical (PFC)-limbic signalling of endocannabinoids (anandamide) and altered hormonal activity (prolactin and glucocorticoids). Behavioural therapies such as cognitive-behavioural/remediation therapies ameliorate symptoms by enhancing perceived controllability. There is also evidence that augmenting endocannabinoid and hormonal levels results in antidepressant/anti-stress action. Based on a modified version of the rodent Morris

The emerging therapeutic and recreational use of cannabinoids calls for a better understanding of their brain effects. Using functional ultrasound (fUS) imaging, we studied the dynamics of the alterations of brain activation and functional connectivity (FC) patterns, measured through the neurovascular coupling, in a 60 minutes period following cannabinoid treatment in awake and behaving C57/BL6J mice. We then correlated these changes with important behavioral and molecular readouts, specifically locomotion, analgesia and CB1 receptor (CB1R) activation, measured by CB1R phosphorylation.Results

Temporal lobe epilepsy (TLE) is one of the most prevalent neurological disorders, affecting 1-3% people worldwide. As this type of epilepsy is often refractory to anticonvulsant drugs, it is crucial to advance the understanding of the mechanisms that underlie its pathophysiology. The endocannabinoid system (ECS) protects nerve cells through the cannabinoid CB1 receptor regulation of the glutamatergic neuronal excitability. As TLE patients frequently show changes in the ECS, in this study we analyze the impact of the status epilepticus in the hippocampus four weeks after administraton of the pr

AIMS: The activation of CB1 receptor (CB1R) is reported to favor energy accumulation and promote resiliency against stress. The aim of this study is to elucidate whether CB1R expression in CaMKII+ neurons is sufficient to restore its role in the regulation of energy metabolism and contingent behaviors.METHODS: To this end, we applied a genetic strategy to reconstitute CB1R expression at endogenous levels in CaMKII+ neurons (CaMKII-CB1-RS).RESULTS: The rescue of CB1R expression in these neurons promotes feeding behavior causing fasting-induced hyperphagia, increased motivation and impulsivity t

Given the remarkable cognitive and neuropsychiatric impairments linked to cannabis use, most of the anatomical and functional data on the endocannabinoid (ECB) system has been gathered from higher brain regions like the prefrontal cortex, leaving aside structures that integrate the sensory systems. However, considering the conservation of cortical organization across areas and species, studying the latter would not only impact the understanding of the perceptual effects of cannabinoids, but potentially provide insights into the neural circuits involved in more complex behaviours.To this end, w

Although traditionally thought to act primarily in the spinal cord, emerging evidence support important inhibitory functions by glycinergic transmission in the brain. In the ventral pallidum (VP), glycinergic afferents from the brainstem make synapses onto cholinergic interneurons to regulate arousal. Notably, VP is comprised of a heterogeneous population of GABAergic neurons, of which those that express somatostatin (SOM+) comprise a significant group and have been implicated in the control of sleep and wakefulness directly inhibiting cholinergic, glutamatergic and parvalbumin neurons. Here,

Aging is epitomized by a progressive increase in neuroinflammation which is associated with altered brain states, neuronal death and eventually neurodegeneration disease. Microglia are the resident macrophagic cells of the brain that play a crucial role in maintaining homeostasis and immune response especially during neuroinflammation. The endocannabinoid system (ECS) is a negative feedback signalling system that helps to maintain homeostasis. The ECS is able to modulate microglia activation states and functions through the endocannabinoid receptors CB1 and CB2. Although, the role of ECS and m

GABAergic neurotransmission generates two types of inhibitions: the transient activation of synaptic GABA receptors, or phasic inhibition, which elicits inhibitory postsynaptic currents, and the activation of extrasynaptic GABA receptors by “ambient” GABA which causes a persistent, “tonic”, inhibition that finely tunes cellular excitability of target neurons. Change in GABA synaptic efficacy is a crucial mechanism that underlies experience-dependent modifications of brain function. Several forms of GABA synaptic plasticity require retrograde signaling by endocannabinoids (eCB) through the acti

Adolescence binge drinking impacts on cognition and behavior through the brain endocannabinoid system (ECS). Dietary long-chain polyunsaturated omega-3 (n-3) fatty acids increase hippocampal synaptic transmission and improve memory functions. Strikingly, alcohol (EtOH) decreases n-3 in the brain, having a negative effect on synaptic plasticity. Because adolescent binge drinking causes long-term impairment of the cannabinoid-dependent synaptic plasticity at the excitatory medial perforant path (MPP) synapses of the hippocampal dentate gyrus (Peñasco et al., 2020), we hypothesize that n-3 could