The gut microbiota in persistent post-operative pain following breast cancer surgery.

Persistent post-surgical pain (PPSP) is defined as pain which continues after a surgical operation in a significant form for at least three months (and is not related to pre-existing painful conditions). PPSP is a common, under-recognised, and important clinical problem which affects millions of patients worldwide. Preventative measures which are currently available include the selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen.

Ventral hippocampal diacylglycerol lipase-alpha deletion decreases avoidance behaviors and alters excitation-inhibition balance.

The endogenous cannabinoid, 2-arachidonoylglycerol (2-AG), plays a key role in the regulation of anxiety- and stress-related behavioral phenotypes and may represent a novel target for the treatment of anxiety disorders. However, recent studies have suggested a more complex role for 2-AG signaling in the regulation of stress responsivity, including increases in acute fear responses after 2-AG augmentation under some conditions. Thus, 2-AG signaling within distinct brain regions and circuits could regulate anxiety-like behavior and stress responsivity in opposing manners.

Endogenous cannabinoids are required for MC4R-mediated control of energy homeostasis.

Hypothalamic regulation of feeding and energy expenditure is a fundamental and evolutionarily conserved neurophysiological process critical for survival. Dysregulation of these processes, due to environmental or genetic causes, can lead to a variety of pathological conditions ranging from obesity to anorexia. Melanocortins and endogenous cannabinoids (eCBs) have been implicated in the regulation of feeding and energy homeostasis; however, the interaction between these signaling systems is poorly understood.

Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors.

Recent studies have demonstrated anxiolytic potential of pharmacological endocannabinoid (eCB) augmentation approaches in a variety of preclinical models. Pharmacological inhibition of endocannabinoid-degrading enzymes, such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), elicit promising anxiolytic effects in rodent models with limited adverse behavioral effects, however, the efficacy of dual FAAH/MAGL inhibition has not been investigated. In the present study, we compared the effects of FAAH (PF-3845), MAGL (JZL184) and dual FAAH/MAGL (JZL195) inhibitors on (1) anxiety-like behaviors under non-stressed and stressed conditions, (2) locomotor activity and body temperature, (3) lipid levels in the brain and (4) cognitive functions.

Phasic Dopamine Signals in the Nucleus Accumbens that Cause Active Avoidance Require Endocannabinoid Mobilization in the Midbrain.

Phasic dopamine (DA) release accompanies approach toward appetitive cues. However, a role for DA in the active avoidance of negative events remains undetermined. Warning signals informing footshock avoidance are associated with accumbal DA release, whereas depression of DA is observed with unavoidable footshock.

Role of Striatal Direct Pathway 2-Arachidonoylglycerol Signaling in Sociability and Repetitive Behavior.

Background: Endocannabinoid signaling plays an important role in regulating synaptic transmission in the striatum, a brain region implicated as a central node of dysfunction in autism spectrum disorder. Deficits in signaling mediated by the endocannabinoid 2-arachidonoylglycerol (2-AG) have been reported in mouse models of autism spectrum disorder, but a causal role for striatal 2-AG deficiency in phenotypes relevant to autism spectrum disorder has not been explored.

Methods: Using conditional knockout mice, we examined the electrophysiological, biochemical, and behavioral effects of 2-AG deficiency by deleting its primary synthetic enzyme, diacylglycerol lipase α (DGLα), from dopamine D receptor-expressing or adenosine A2a receptor-expressing medium spiny neurons (MSNs) to determine the role of 2-AG signaling in striatal direct or indirect pathways, respectively.

Eosinophilic myocarditis as a first presentation of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

We present the case of a 28-year-old man who presented with chest pain and elevated cardiac biomarkers, with no evidence of acute ischaemia. He had a pronounced eosinophilia, abnormal echocardiographic, cardiac MRI and CT findings. He underwent transbronchial biopsy of carinal lymph nodes and of lung parenchyma.

Endocannabinoid signalling modulates susceptibility to traumatic stress exposure.

Stress is a ubiquitous risk factor for the exacerbation and development of affective disorders including major depression and posttraumatic stress disorder. Understanding the neurobiological mechanisms conferring resilience to the adverse consequences of stress could have broad implications for the treatment and prevention of mood and anxiety disorders. We utilize laboratory mice and their innate inter-individual differences in stress-susceptibility to demonstrate a critical role for the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) in stress-resilience.

Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.

Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors.

Ketamine and MAG Lipase Inhibitor-Dependent Reversal of Evolving Depressive-Like Behavior During Forced Abstinence From Alcohol Drinking.

Although alcoholism and depression are highly comorbid, treatment options that take this into account are lacking, and mouse models of alcohol (ethanol (EtOH)) intake-induced depressive-like behavior have not been well established. Recent studies utilizing contingent EtOH administration through prolonged two-bottle choice access have demonstrated depression-like behavior following EtOH abstinence in singly housed female C57BL/6J mice. In the present study, we found that depression-like behavior in the forced swim test (FST) is revealed only after a protracted (2 weeks), but not acute (24 h), abstinence period.

Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA.

Genetic disruption of 2-arachidonoylglycerol synthesis reveals a key role for endocannabinoid signaling in anxiety modulation.

Endocannabinoid (eCB) signaling has been heavily implicated in the modulation of anxiety and depressive behaviors and emotional learning. However, the role of the most-abundant endocannabinoid 2-arachidonoylglycerol (2-AG) in the physiological regulation of affective behaviors is not well understood. Here, we show that genetic deletion of the 2-AG synthetic enzyme diacylglycerol lipase α (DAGLα) in mice reduces brain, but not circulating, 2-AG levels.

Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation.

Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using the light-dark box assay and novelty-induced hypophagia test.

The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury.

Traumatic brain injury (TBI) is the leading cause of death in young adults in the United States, but there is still no effective agent for treatment. N-arachidonoylethanolamine (anandamide, AEA) is a major endocannabinoid in the brain. Its increase after brain injury is believed to be protective.

Multiple mechanistically distinct modes of endocannabinoid mobilization at central amygdala glutamatergic synapses.

The central amygdala (CeA) is a key structure at the limbic-motor interface regulating stress responses and emotional learning. Endocannabinoid (eCB) signaling is heavily implicated in the regulation of stress-response physiology and emotional learning processes; however, the role of eCBs in the modulation of synaptic efficacy in the CeA is not well understood. Here we describe the subcellular localization of CB1 cannabinoid receptors and eCB synthetic machinery at glutamatergic synapses in the CeA and find that CeA neurons exhibit multiple mechanistically and temporally distinct modes of postsynaptic eCB mobilization.

River otters as biomonitors for organochlorine pesticides, PCBs, and PBDEs in Illinois.

The North American river otter (Lontra canadensis) is a biomonitor for organohalogenated compounds (OHCs) associated with a wide range of deleterious health effects in wildlife and humans. We determined concentrations of twenty OHCs in livers of 23 river otters salvaged by the Illinois Department of Natural Resources from 2009 to 2011, determined sex-dependent distribution of OHCs, and compared our results to the reported concentrations of four OHCs in Illinois river otters from 1984 to 1989. Since these contaminants have been banned for over 30 years, we predicted smaller mean concentrations than those previously reported in Illinois otters.