Search results for " cannabinoid"
showing 10 items of 163 documents
Inhibition by Anandamide and Synthetic Cannabimimetics of the Release of [3H]d-Aspartate and [3H]GABA from Synaptosomes Isolated from the Rat Hippoca…
2004
Cannabinoids (CB) can act as retrograde synaptic mediators of depolarization-induced suppression of inhibition or excitation in hippocampus. This mechanism may underlie the impairment of some cognitive processes produced by these compounds, including short-term memory formation in the hippocampus. In this study, we investigated several compounds known to interact with CB receptors, evaluating their effects on K +-evoked release of [ 3H]d-aspartate ([ 3H]d-ASP) and [ 3H]GABA from superfused synaptosomes isolated from the rat hippocampus. [ 3H]d-ASP and [ 3H]GABA release were inhibited to different degrees by the synthetic cannabinoids WIN 55,212-2; CP 55,940, and arachidonyl-2′- chloroethyla…
A runner’s high depends on cannabinoid receptors in mice
2015
Exercise is rewarding, and long-distance runners have described a runner's high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of pe…
Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.
2009
Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis. Moreover, using pharmacological and genetic tools, we found that THC long-term memory deficits …
Assessment of the abuse potential of MDMA in the conditioned place preference paradigm: Role of CB1 receptors
2013
Numerous reports have highlighted the role of the endocannabinoid system in the addictive potential of MDMA (3,4-methylenedioxy-methamphetamine). A previous report showed that CB1 knockout (KOCB1) mice do not acquire MDMA self-administration, despite developing conditioned place preference (CPP). This contradiction could be due to the particular procedure of place conditioning used. The present work compares MDMA-induced CPP in KOCB1 mice using unbiased and biased procedures of place conditioning. In the unbiased procedure, MDMA induced CPP and reinstatement of the extinguished preference in wild type (WT) mice, but not in KOCB1 mice. In contrast, in a biased protocol of CPP, MDMA produced …
Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation
2016
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. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific ce…
Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.
2010
Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models. However, the pathophysiological impact of this loss of receptors in Huntington's disease is as yet unknown. Here, we generated a double-mutant mouse model that expresses human mutant huntingtin exon 1 in a type 1 cannabinoid receptor-null background, and found that receptor deletion aggravates the symptoms, neuropatholog…
Understanding Cannabinoid Psychoactivity with Mouse Genetic Models
2007
Marijuana and its main psychotropic ingredient Δ9-tetrahydrocannabinol (THC) exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1), which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release γ aminobutyric acid), cortical glutamatergic neurons, and neurons expres…
Prenatal exposure to the CB1 receptor agonist WIN 55,212-2 causes learning disruption associated with impaired cortical NMDA receptor function and em…
2005
The aim of this study was to investigate whether prenatal exposure to the cannabinoid CB1 receptor agonist WIN 55,212-2 (WIN) at a daily dose devoid of overt signs of toxicity and/or gross malformations (0.5 mg/kg, gestation days 5-20), influences cortical glutamatergic neurotransmission, learning and emotional reactivity in rat offspring. Basal and K+-evoked extracellular glutamate levels were significantly lower in cortical cell cultures obtained from pups exposed to WIN during gestation with respect to those measured in cultures obtained from neonates born from vehicle-treated dams. The addition of NMDA to cortical cell cultures from neonates born from vehicle-treated dams concentration-…
Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine.
2013
This study was aimed to evaluate the involvement of CB2 cannabinoid receptors (CB2r) in the rewarding, reinforcing and motivational effects of nicotine. Conditioned place preference (CPP) and intravenous self-administration experiments were carried out in knockout mice lacking CB2r (CB2KO) and wild-type (WT) littermates treated with the CB2r antagonist AM630 (1 and 3 mg/kg). Gene expression analyses of tyrosine hydroxylase (TH) and α3- and α4-nicotinic acetylcholine receptor subunits (nAChRs) in the ventral tegmental area (VTA) and immunohistochemical studies to elucidate whether CB2r colocalized with α3- and α4-nAChRs in the nucleus accumbens and VTA were performed. Mecamylamine-precipitat…
The endocannabinoid system controls food intake via olfactory processes
2014
Comment in Sensory systems: the hungry sense. [Nat Rev Neurosci. 2014] Inhaling: endocannabinoids and food intake. [Nat Neurosci. 2014]; International audience; Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoid…