Helping You Find Full Text Journal Articles

Search Results:

Author: Matthew N Hill (94)


Dec
2017

Exposure to a traumatic event may result in the development of post-traumatic stress disorder (PTSD). Endocannabinoids are crucial modulators of the stress response, interfere with excessive retrieval and facilitate the extinction of traumatic memories. Exposure therapy, combined with pharmacotherapy, represents a promising tool for PTSD treatment.

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2018


View Full Text PDF Listings View primary source full text article PDFs.

Jan
2018

Exposure to stress is an undeniable, but in most cases surmountable, part of life. However, in certain individuals, exposure to severe or cumulative stressors can lead to an array of pathological conditions including posttraumatic stress disorder (PTSD), characterized by debilitating trauma-related intrusive thoughts, avoidance behaviors, hyperarousal, as well as depressed mood and anxiety. In the context of the rapidly changing political and legal landscape surrounding use of cannabis products in the USA, there has been a surge of public and research interest in the role of cannabinoids in the regulation of stress-related biological processes and in their potential therapeutic application for stress-related psychopathology.

View Full Text PDF Listings View primary source full text article PDFs.

Oct
2017

Endocannabinoids: Effectors of glucocorticoid signaling.

Front Neuroendocrinol 2017 Oct 21;47:86-108. Epub 2017 Jul 21.
Georgia Balsevich, Gavin N Petrie, Matthew N Hill
For decades, there has been speculation regarding the interaction of cannabinoids with glucocorticoid systems. Given the functional redundancy between many of the physiological effects of glucocorticoids and cannabinoids, it was originally speculated that the biological mechanisms of cannabinoids were mediated by direct interactions with glucocorticoid systems. With the discovery of the endocannabinoid system, additional research demonstrated that it was actually the opposite; glucocorticoids recruit endocannabinoid signaling, and that the engagement of endocannabinoid signaling mediated many of the neurobiological and physiological effects of glucocorticoids.

View Full Text PDF Listings View primary source full text article PDFs.

Sep
2017

Alcohol dependence is associated with anxiety during withdrawal. The endocannabinoid (ECB) system participates in the neuroendocrine and behavioral response to stress and changes in corticolimbic ECB signaling may contribute to alcohol withdrawal-induced anxiety. Moreover, symptoms of alcohol withdrawal differ between sexes and sexual dimorphism in withdrawal-induced ECB recruitment may be a contributing factor.

View Full Text PDF Listings View primary source full text article PDFs.

Apr
2017

Stressor exposure is a predisposing risk factor for many psychiatric conditions such as PTSD and depression. However, stressors do not influence all individuals equally and in response to an identical stressor some individuals may be vulnerable while others are resilient. While various biological and behavioral factors contribute to vulnerability versus resilience, an individual's degree of control over the stressor is among the most potent.

View Full Text PDF Listings View primary source full text article PDFs.

Aug
2017

Imaging genetics and genomics research has begun to provide insight into the molecular and genetic architecture of neural phenotypes and the neural mechanisms through which genetic risk for psychopathology may emerge. As it approaches its third decade, imaging genetics is confronted by many challenges, including the proliferation of studies using small sample sizes and diverse designs, limited replication, problems with harmonization of neural phenotypes for meta-analysis, unclear mechanisms, and evidence that effect sizes may be more modest than originally posited, with increasing evidence of polygenicity. These concerns have encouraged the field to grow in many new directions, including the development of consortia and large-scale data collection projects and the use of novel methods (e.

View Full Text PDF Listings View primary source full text article PDFs.

Mar
2017

Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties.

View Full Text PDF Listings View primary source full text article PDFs.

View Full Text PDF Listings View primary source full text article PDFs.

Aug
2016

Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties.

View Full Text PDF Listings View primary source full text article PDFs.

Dec
2016

Systemic activation of cannabinoid receptors often induces biphasic effects on emotional memory and anxiety depending on the levels of emotional arousal associated to the experimental context. The basolateral nucleus of the amygdala (BLA) represents a crucial structure for the ability of endocannabinoid (eCB) signaling to modulate emotional behaviour, and receives dense projections from brainstem arousal system nuclei. We examined whether changes in emotional arousal state would influence the ability of acute eCB manipulations within the BLA to modulate anxiety.

View Full Text PDF Listings View primary source full text article PDFs.

Dec
1969

PAK1 inhibitors are known to markedly improve social and cognitive function in several animal models of brain disorders, including autism, but the underlying mechanisms remain elusive. We show here that disruption of PAK1 in mice suppresses inhibitory neurotransmission through an increase in tonic, but not phasic, secretion of endocannabinoids (eCB). Consistently, we found elevated levels of anandamide (AEA), but not 2-arachidonoylglycerol (2-AG) following PAK1 disruption.

View Full Text PDF Listings View primary source full text article PDFs.

View Full Text PDF Listings View primary source full text article PDFs.

Apr
2016

Sustained exposure to stress or corticosteroids is known to cause changes in brain endocannabinoid (eCB) signaling, such that tissue contents of the eCBs N-arachidonylethanolamine (AEA) are generally reduced while 2-arachidonoylglycerol (2-AG) levels increase. These changes in eCB signaling are important for many of the aspects of chronic stress, such as anxiety, reward sensitivity and stress adaptation, yet the mechanisms mediating these changes are not fully understood. We have recently found that the stress-related neuropeptide corticotropin-releasing hormone (CRH), acting through the CRH type 1 receptor (CRHR1), can reduce AEA content by increasing its hydrolysis by the enzyme fatty acid amide hydrolase (FAAH) as well as increase 2-AG contents.

View Full Text PDF Listings View primary source full text article PDFs.

Dec
1969

Tryptophan is an essential dietary amino acid that is necessary for protein synthesis, but also serves as the precursor for serotonin. However, in addition to these biological functions, tryptophan also serves as a precursor for the kynurenine pathway, which has neurotoxic (quinolinic acid) and neuroprotective (kynurenic acid) metabolites. Glucocorticoid hormones and inflammatory mediators, both of which are increased by stress, have been shown to bias tryptophan along the kynurenine pathway and away from serotonin synthesis; however, to date, there is no published data regarding the effects of stress on enzymes regulating the kynurenine pathway in a regional manner throughout the brain.

View Full Text PDF Listings View primary source full text article PDFs.

Oct
2015

Variations in environmental aversiveness influence emotional memory processes in rats. We have previously shown that cannabinoid effects on memory are dependent on the stress level at the time of training as well as on the aversiveness of the environmental context. Here, we investigated whether the hippocampal endocannabinoid system modulates memory retrieval depending on the training-associated arousal level.

View Full Text PDF Listings View primary source full text article PDFs.

Dec
2015

Endocannabinoid (eCB) signaling plays an important role in the stress response pathways of the mammalian brain, yet its role in the avian stress response has not been described. Understanding eCB signaling in avian species (such as the European starling, Sturnus vulgaris) allows a model system that exhibits natural attenuation of hypothalamic-pituitary-adrenal (HPA) responsiveness to stressors. Specifically, seasonally breeding birds exhibit the highest HPA activity during the breeding season and subsequently exhibit a robust HPA down-regulation during molt.

View Full Text PDF Listings View primary source full text article PDFs.

Oct
2015

Methods for quantifying anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are needed to support programs investigating molecular mechanisms of the central nervous system. Existing methods, while useful, are not well adapted to efficiently process large numbers of very small tissue samples. A unique challenge involves the disparity in endogenous levels of AEA (pmol/g tissue) and 2-AG (nmol/g tissue).

View Full Text PDF Listings View primary source full text article PDFs.

Oct
2015

The brain is the central organ involved in perceiving and adapting to social and physical stressors via multiple interacting mediators, from the cell surface to the cytoskeleton to epigenetic regulation and nongenomic mechanisms. A key result of stress is structural remodeling of neural architecture, which may be a sign of successful adaptation, whereas persistence of these changes when stress ends indicates failed resilience. Excitatory amino acids and glucocorticoids have key roles in these processes, along with a growing list of extra- and intracellular mediators that includes endocannabinoids and brain-derived neurotrophic factor (BDNF).

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2016

There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. The aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of a wide range of inflammatory mediators across a broad temporal range, in key corticolimbic brain regions involved in the regulation of the stress response (amygdala, hippocampus, hypothalamus, medial prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30min or 120min of acute restraint stress and protein levels were examined 0h through 24h post-termination of 120min of acute restraint stress using both multiplex and ELISA methods.

View Full Text PDF Listings View primary source full text article PDFs.

Dec
2015

The endocannabinoid (eCB) system is known to regulate neural, endocrine and behavioral responses to stress in adults; however there is little knowledge regarding how this system governs the development and maturation of these responses. Previous work has reported dynamic and time-specific changes in CB1 receptor expression, N-arachidonylethanolamine (AEA) content and fatty acid amide hydrolase (FAAH) activity within corticolimbic structures throughout the peri-adolescent period. To examine whether fluctuations in adolescent eCB activity contribute to the development of adult stress responsivity and emotionality, we treated male Sprague-Dawley rats daily with the CB1R antagonist, AM-251 (5 mg/kg), or vehicle between post-natal days (PND) 35-45.

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2016

Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes. A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response. In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling have with respect to many of the effects of stress.

View Full Text PDF Listings View primary source full text article PDFs.

Aug
2015

To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats. JZL195, administered at the dose of 0.

View Full Text PDF Listings View primary source full text article PDFs.

Mar
2015

Collapse of endocannabinoid (eCB) signaling in the amygdala contributes to stress-induced anxiety, but the mechanisms of this effect remain unclear. eCB production is tied to the function of the glutamate receptor mGluR5, itself dependent on tyrosine phosphorylation. Herein, we identify a novel pathway linking eCB regulation of anxiety through phosphorylation of mGluR5.

View Full Text PDF Listings View primary source full text article PDFs.

Mar
2015

Corticotropin-releasing hormone (CRH) is a central integrator in the brain of endocrine and behavioral stress responses, whereas activation of the endocannabinoid CB1 receptor suppresses these responses. Although these systems regulate overlapping functions, few studies have investigated whether these systems interact. Here we demonstrate a novel mechanism of CRH-induced anxiety that relies on modulation of endocannabinoids.

View Full Text PDF Listings View primary source full text article PDFs.

Mar
2015

Cross-species studies enable rapid translational discovery and produce the broadest impact when both mechanism and phenotype are consistent across organisms. We developed a knock-in mouse that biologically recapitulates a common human mutation in the gene for fatty acid amide hydrolase (FAAH) (C385A; rs324420), the primary catabolic enzyme for the endocannabinoid anandamide. This common polymorphism impacts the expression and activity of FAAH, thereby increasing anandamide levels.

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2015

To stress or not to stress: a question of models.

Curr Protoc Neurosci 2015 Jan 5;70:8.33.1-22. Epub 2015 Jan 5.
J Megan Gray, Francis Chaouloff, Matthew N Hill
Stress research is a rapidly evolving field that encompasses numerous disciplines ranging from neuroscience to metabolism. With many new researchers migrating into the field, navigating the hows and whys of specific research questions can sometimes be enigmatic given the availability of so many models in the stress field. Additionally, as with every field, there are many seemingly minor experimental details that can have dramatic influences on data interpretation, although many of these are unknown to those not familiar with the field.

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2015

Glucocorticoids are known to promote the development of metabolic syndrome through the modulation of both feeding pathways and metabolic processes; however, the precise mechanisms of these effects are not well-understood. Recent evidence shows that glucocorticoids possess the ability to increase endocannabinoid signaling, which is known to regulate appetite, energy balance, and metabolic processes through both central and peripheral pathways. The aim of this study was to determine the role of endocannabinoid signaling in glucocorticoid-mediated obesity and metabolic syndrome.

View Full Text PDF Listings View primary source full text article PDFs.

Feb
2015

Subcallosal cingulate (SCC) deep brain stimulation (DBS) is a promising experimental treatment for treatment-resistant depression (TRD). Given the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity and antidepressant efficacy, we examined the effect of SCC-DBS on serum BDNF in TRD.
Four patients with TRD underwent SCC-DBS treatment.

View Full Text PDF Listings View primary source full text article PDFs.

Sep
2014

The medial prefrontal cortex (mPFC) is known to regulate higher order processes like cognitive flexibility. Accumulating behavioral evidence suggests that endocannabinoid (eCB) signaling regulates neuronal architecture within the PFC, as well as certain forms of cognitive flexibility; however, all of these studies have been performed in male rodents and it is currently unknown whether the eCB system performs a similar role in females. To this extent, dendritic morphology of layer II/III neurons in the infra- and prelimbic regions of the mPFC was analyzed and cognitive ability and flexibility in a fixed-platform Morris water maze task was assessed in adult female CB1 receptor knockout (CB1KO) mice.

View Full Text PDF Listings View primary source full text article PDFs.

May
2014

The prefrontal cortex (PFC) provides executive control of the brain in humans and rodents, coordinating cognitive, emotional, and behavioral responses to threatening stimuli and subsequent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. The endocannabinoid system has emerged as a fundamental regulator of HPA axis feedback inhibition and an important modulator of emotional behavior. However, the precise role of endocannabinoid signaling within the PFC with respect to stress coping and emotionality has only recently been investigated.

View Full Text PDF Listings View primary source full text article PDFs.

View Full Text PDF Listings View primary source full text article PDFs.

Nov
2013

A long-standing literature linking endocannabinoids (ECBs) to stress, fear, and anxiety has led to growing interest in developing novel anxiolytics targeting the ECB system. Following rapid on-demand biosynthesis and degradation upon neuronal activation, the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH). Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in a key anxiety-mediating region--the basolateral amygdala (BLA).

View Full Text PDF Listings View primary source full text article PDFs.

Oct
2013

Accumulating evidence over the past decade has highlighted an important role of the endocannabinoid (eCB) system in the regulation of stress and emotional behavior across divergent species, from rodents to humans. The general findings from this work indicate that the eCB system plays an important role in gating and buffering the stress response, dampening anxiety and regulating mood. Work in rodents has allowed researchers to determine the neural mechanisms mediating this relationship while work in human populations has demonstrated the possible importance of this system in stress-related psychiatric diseases, such as post-traumatic stress disorder, generalized anxiety and major depression.

View Full Text PDF Listings View primary source full text article PDFs.

Nov
2013

Obesity is a growing public health problem. Although convenient, the notion that obesity is simply a problem of will power is increasingly antiquated. It is becoming clear that complex interactions of environment, neurohormonal systems, and transgenerational effects directly contribute to obesity.

View Full Text PDF Listings View primary source full text article PDFs.

Mar
2014

Cannabinoid exposure during adolescence has adverse effects on neuroplasticity, emotional behavior, cognition, and reward sensitivity in adult rats. We investigated whether escalating doses of the cannabinoid receptor 1 (CB1 R) agonist, HU-210, in adolescence would affect adult hippocampal neurogenesis and behavioral processes putatively modulated by hippocampal neurogenesis, in adult male and female Sprague-Dawley rats. Escalating doses of HU-210 (25, 50, and 100 µg/kg), or vehicle were administered from postnatal day (PND) 35 to 46.

View Full Text PDF Listings View primary source full text article PDFs.

Dec
2013

Endocannabinoid (eCB) signaling has been identified as a modulator of adaptation to stress, and is integral to basal and stress-induced glucocorticoid regulation. Furthermore, interactions between eCBs and glucocorticoids have been shown to be necessary for the regulation of emotional memories, suggesting that eCB function may relate to the development of post-traumatic stress disorder (PTSD). To examine this, plasma eCBs were measured in a sample (n=46) drawn from a population-based cohort selected for physical proximity to the World Trade Center (WTC) at the time of the 9/11 attacks.

View Full Text PDF Listings View primary source full text article PDFs.

Oct
2013

Multiple sclerosis (MS) is often associated with co-morbid behavioural and cognitive impairments; however the presence of these symptoms does not necessarily correlate with neurological damage. This suggests that an alternate mechanism may subserve these impairments relative to motor deficits. We investigated whether these abnormalities could be studied in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2013

Fatty acid amide hydrolase (FAAH) regulates tissue concentrations of N-acylethanolamines (NAEs), including the endocannabinoid, N-arachidonylethanolamide (anandamide, AEA). FAAH activity and NAEs are widely distributed throughout the brain and FAAH activity regulates an array of processes including emotion, cognition, inflammation, and feeding. However, there is relatively little research describing how this system develops throughout adolescence, particularly within limbic circuits regulating stress and reward processing.

View Full Text PDF Listings View primary source full text article PDFs.

Oct
2012

The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder.

View Full Text PDF Listings View primary source full text article PDFs.

Jun
2012

Several lines of evidence point to the potential role of the endocannabinoid system in female sexual functioning. These include results from studies describing the subjective effects of exogenous cannabinoids on sexual functioning in humans and the observable effects of exogenous cannabinoids on sexual functioning in other species, as well as results from studies investigating the location of cannabinoid receptors in the brain and periphery, and the effects of cannabinoid receptor activation on neurotransmitters implicated in sexual functioning. While these lines of research suggest a role for the endocannabinoid system in female sexual functioning, no studies investigating the relationship between concentrations of endogenous cannabinoids (i.

View Full Text PDF Listings View primary source full text article PDFs.

Feb
2012

Depression is known to be a risk factor for cardiovascular diseases but the underlying mechanisms remain unclear. Since recent preclinical evidence suggests that endogenous agonists of cannabinoid receptors (endocannabinoids) are involved in both cardiovascular function and depression, we asked whether endocannabinoids correlated with either in humans.
Resting blood pressure and serum content of endocannabinoids in ambulatory, medication-free, female volunteers with depression (n = 28) and their age- and ethnicity-matched controls (n = 27) were measured.

View Full Text PDF Listings View primary source full text article PDFs.

Sep
2012

The endocannabinoid system has recently emerged as a vital component of the stress response and is an appealing target for the treatment of mood and anxiety disorders. Additionally, corticolimbic endocannabinoid signaling is important for stress-induced regulation of emotional behavior. However, the mechanism by which this occurs remains elusive.

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2012

Exposure to behavioural stress normally triggers a complex, multilevel response of the hypothalamic-pituitary-adrenal (HPA) axis that helps maintain homeostatic balance. Although the endocannabinoid (eCB) system (ECS) is sensitive to chronic stress, few studies have directly addressed its response to acute stress. Here we show that acute restraint stress enhances eCB-dependent modulation of GABA release measured by whole-cell voltage clamp of inhibitory postsynaptic currents (IPSCs) in rat hippocampal CA1 pyramidal cells in vitro.

View Full Text PDF Listings View primary source full text article PDFs.

Jul
2011

The mechanisms subserving the ability of glucocorticoid signaling within the medial prefrontal cortex (mPFC) to terminate stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis are not well understood. We report that antagonism of the cannabinoid CB(1) receptor locally within the mPFC prolonged corticosterone secretion following cessation of stress in rats. Mice lacking the CB(1) receptor exhibited a similar prolonged response to stress.

View Full Text PDF Listings View primary source full text article PDFs.

Jan
2012

Nearly 12% of US children are exposed to intense adverse experiences. Research has demonstrated that these experiences can negatively impact adult health, often resulting in psychopathology. Less attention, however, is given to the impact of childhood adverse experiences on childhood health and wellbeing.

View Full Text PDF Listings View primary source full text article PDFs.

Sep
2011

Many changes produced by chronic stress are similar to those seen in cannabinoid CB(1) receptor-deficient mice. In the current study, we examined both anxiety-like behavior and dendritic complexity within the prefrontal cortex and basolateral amygdala (BLA) in wild-type and CB(1) receptor-deficient mice, under basal conditions and following exposure to 21 days of protracted restraint stress. CB(1) receptor-deficient mice exhibited increased indices of anxiety in the elevated plus maze under basal conditions that were similar in magnitude to changes seen in wild-type mice exposed to chronic stress.

View Full Text PDF Listings View primary source full text article PDFs.

Aug
2011

Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants.

Prog Neuropsychopharmacol Biol Psychiatry 2011 Aug 24;35(7):1575-85. Epub 2010 Nov 24.
Boris B Gorzalka, Matthew N Hill
In the last few years, there have been several advances in the determination of the role of the endocannabinoid system in the etiology of depression and the functional actions of antidepressant drugs. Specifically, a deficiency in endocannabinoid signaling is sufficient to produce a "depressive-like" phenotype at the preclinical level (including changes in rewarding, emotional and cognitive behavior and biological changes such as increased HPA axis activity, impaired stress adaptation, reduced neurogenesis and altered serotonin negative feedback), and capable of inducing symptoms of depression in humans at a clinical level. In line with these findings, clinical populations diagnosed with depression are found to have reduced levels of circulating endocannabinoids and preclinical models of depression reveal a deficit in central endocannabinoid signaling.

View Full Text PDF Listings View primary source full text article PDFs.

Nov
2010

Endocannabinoid signaling is distributed throughout the brain, regulating synaptic release of both excitatory and inhibitory neurotransmitters. The presence of endocannabinoid signaling within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures such as the amygdala, suggests it may play an important role in regulating the neuroendocrine and behavioral effects of stress. The evidence reviewed here demonstrates that endocannabinoid signaling is involved in both activating and terminating the hypothalamic-pituitary-adrenal axis response to both acute and repeated stress.

View Full Text PDF Listings View primary source full text article PDFs.

Nov
2010

The amygdala is a sexually dimorphic brain region critical for the regulation of social, cognitive, and emotional behaviors, but both the nature and the source of sex differences in the amygdala are largely unknown. We have identified a unique sex difference in the developing rat medial amygdala (MeA) that is regulated by cannabinoids. Newborn females had higher rates of cell proliferation than males.

View Full Text PDF Listings View primary source full text article PDFs.

Back to top