Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric condition arising from traumatic experiences, marked by abnormal fear memories. Despite women are twice as likely as men to develop PTSD, the biological mechanisms underlying this disparity remain inadequately explored, particularly in preclinical studies involving female subjects. Previous research shows that female rats exhibit active fear responses, while males display passive behaviors.
View Article and Find Full Text PDFIncreasing evidence suggests that the neurobiological processes that govern learning and memory can be different in males and females, but many of the specific mechanisms underlying these sex differences have not been fully defined. Here we investigated potential sex differences in endocannabinoid (eCB) modulation of Pavlovian fear conditioning and extinction, examining multiple defensive behaviors, including shock responsivity, conditioned freezing, and conditioned darting. We found that while systemic administration of drugs acting on eCB receptors did not influence the occurrence of darting, females that were classified as Darters responded differently to the drug administration than those classified as Non-darters.
View Article and Find Full Text PDFBackground: Thymus hypoplasia due to stromal cell problems has been linked to mutations in several transcription factors, including Forkhead box N1 (FOXN1). FOXN1 supports T-cell development by regulating the formation and expansion of thymic epithelial cells (TECs). While autosomal recessive FOXN1 mutations result in a nude and severe combined immunodeficiency phenotype, the impact of single-allelic or compound heterozygous FOXN1 mutations is less well-defined.
View Article and Find Full Text PDFIncreasing evidence suggests that the neurobiological processes that govern learning and memory can be different in males and females, and here we asked specifically whether the endocannabinoid (eCB) system could modulate Pavlovian fear conditioning in a sex-dependent manner. Systemic (i.p.
View Article and Find Full Text PDFCurrent practices vary widely regarding the immunological work-up and management of patients affected with defects in thymic development (DTD), which include chromosome 22q11.2 microdeletion syndrome (22q11.2del) and other causes of DiGeorge syndrome (DGS) and coloboma, heart defect, atresia choanae, retardation of growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome.
View Article and Find Full Text PDFPost-traumatic stress disorder (PTSD) is a chronic psychiatric disease resulting from the experience or witnessing of traumatic events. Persistent PTSD symptoms impair patients' daily quality of life, jeopardizing sleep, mood, sociability, and arousal. Recommended psychological or pharmacological interventions are effective only in a small portion of patients and often lead to relapse.
View Article and Find Full Text PDFRepeated seizures result in a persistent maladaptation of endocannabinoid (eCB) signaling, mediated part by anandamide signaling deficiency in the basolateral amygdala (BLA) that manifests as aberrant synaptic function and altered emotional behavior. Here, we determined the effect of repeated seizures (kindling) on 2-arachidonoylglycerol (2-AG) signaling on GABA transmission by directly measuring tonic and phasic eCB-mediated retrograde signaling in an BLA slice preparation from male rats. We report that both activity-dependent and muscarinic acetylcholine receptor (mAChR)-mediated depression of GABA synaptic transmission was reduced following repeated seizure activity.
View Article and Find Full Text PDF22q11.2 deletion syndrome (22q11.2DS) is the most common human chromosomal microdeletion, causing developmentally linked congenital malformations, thymic hypoplasia, hypoparathyroidism, and/or cardiac defects.
View Article and Find Full Text PDFAutism spectrum disorder (ASD) has a multifactorial etiology. Major efforts are underway to understand the neurobiological bases of ASD and to develop efficacious treatment strategies. Recently, the use of cannabinoid compounds in children with neurodevelopmental disorders including ASD has received increasing attention.
View Article and Find Full Text PDFResearch over the past few decades has established a role for the endocannabinoid system in contributing to the neural and endocrine responses to stress exposure. The two endocannabinoid ligands, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), both play roles in regulating the stress response and both exhibit dynamic changes in response to stress exposure. Most of this previous research, however, was conducted in male rodents.
View Article and Find Full Text PDFNeurosci Biobehav Rev
July 2022
Organisms ranging from plants to higher mammals have developed 24-hour oscillation rhythms to optimize physiology to environmental changes and regulate a plethora of neuroendocrine and behavioral processes, including neurotransmitter and hormone regulation, stress response and learning and memory function. Compelling evidence indicates that a wide array of memory processes is strongly influenced by stress- and emotional arousal-activated neurobiological systems, including the endocannabinoid system which has been extensively shown to play an integral role in mediating stress effects on memory. Here, we review findings showing how circadian rhythms and time-of-day influence stress systems and memory performance.
View Article and Find Full Text PDFIn recent years there has been an increase in the development of new synthetic drugs, among which the "bath salt" 3,4-methylenedioxypyrovalerone (MDPV), a psychostimulant with a mechanism of action similar to those of cocaine and amphetamine, stands out. Drugs of abuse have been consistently shown to affect memory function in male rodents. We have recently shown that amphetamine and MDPV induce generalization of fear memory in an inhibitory avoidance discrimination task in male rats.
View Article and Find Full Text PDFCannabinoids, including derived phytocannabinoids and endogenous cannabinoids (endocannabinoids), are typically considered anti-inflammatory. One such endocannabinoid is -arachidonoylethanolamine (anandamide, AEA), which is metabolized by fatty acid amide hydrolase (FAAH). In humans, there is a loss of function single nucleotide polymorphism (SNP) in the FAAH gene (C385A, rs324420), that leads to increases in the levels of AEA.
View Article and Find Full Text PDFThe brain's endocannabinoid system is a powerful controller of neurotransmitter release, shaping synaptic communication under physiological and pathological conditions. However, our understanding of endocannabinoid signaling in vivo is limited by the inability to measure their changes at timescales commensurate with the high lability of lipid signals, leaving fundamental questions of whether, how, and which endocannabinoids fluctuate with neural activity unresolved. Using novel imaging approaches in awake behaving mice, we now demonstrate that the endocannabinoid 2-arachidonoylglycerol, not anandamide, is dynamically coupled to hippocampal neural activity with high spatiotemporal specificity.
View Article and Find Full Text PDFPeripheral inflammatory conditions, including those localized to the gastrointestinal tract, are highly comorbid with psychiatric disorders such as anxiety and depression. These behavioral symptoms are poorly managed by conventional treatments for inflammatory diseases and contribute to quality of life impairments. Peripheral inflammation is associated with sustained elevations in circulating glucocorticoid hormones, which can modulate central processes, including those involved in the regulation of emotional behavior.
View Article and Find Full Text PDFSingle prolonged stress (SPS) is an experimental model that recapitulates in rodents some of the core symptoms of post-traumatic stress disorder (PTSD). Although women have a two-fold greater risk to develop PTSD, most preclinical studies have been carried out in males. Furthermore, the long-term effects of behavioral alterations induced by SPS have been rarely investigated.
View Article and Find Full Text PDFTrauma patients treated with ketamine during emergency care present aggravated early post- traumatic stress reaction which is highly predictive of post-traumatic stress disorder (PTSD) development and severity. The use of ketamine in the acute trauma phase may directly or indirectly interfere with neural processes of memory consolidation of the traumatic event, thus leading to the formation of maladaptive memories, a hallmark symptom of PTSD. We have recently shown that ketamine anesthesia, immediately after a traumatic event, enhances memory consolidation and leads to long-lasting alterations of social behavior in rats.
View Article and Find Full Text PDFBackground And Purpose: Women are twice as likely as men to develop post-traumatic stress disorder (PTSD) making the search for biological mechanisms underlying these gender disparities especially crucial. One of the hallmark symptoms of PTSD is an alteration in the ability to extinguish fear responses to trauma-associated cues. In male rodents, the endocannabinoid system can modulate fear extinction and has been suggested as a therapeutic target for PTSD.
View Article and Find Full Text PDFBackground: Cannabinoids induce biphasic effects on memory depending on stress levels. We previously demonstrated that different stress intensities, experienced soon after encoding, impaired rat short-term recognition memory in a time-of-day-dependent manner, and that boosting endocannabinoid anandamide (AEA) levels restored memory performance. Here, we examined if two different stress intensities and time-of-day alter hippocampal endocannabinoid tone, and whether these changes modulate short-term memory.
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