Effects of manipulating prefrontal activity and dopamine D1 receptor signaling in an appetitive feature-negative discrimination learning task.

Healthy cognition requires inhibitory modulation of associative learning; conversely, impaired inhibitory discrimination is implicated in behavioral disorders. The medial prefrontal cortex (mPFC) and its dopamine innervation are key to understanding inhibition and impulsivity. We therefore examined the role of prelimbic and infralimbic cortices in within-subjects appetitive feature-negative learning using microinfusions of (a) the gamma-aminobutyric acid-A receptor agonist muscimol (0.

Dopamine D1-like receptors modulate synchronized oscillations in the hippocampal-prefrontal-amygdala circuit in contextual fear.

Contextual fear conditioning (CFC) is mediated by a neural circuit that includes the hippocampus, prefrontal cortex, and amygdala, but the neurophysiological mechanisms underlying the regulation of CFC by neuromodulators remain unclear. Dopamine D1-like receptors (D1Rs) in this circuit regulate CFC and local synaptic plasticity, which is facilitated by synchronized oscillations between these areas. In rats, we determined the effects of systemic D1R blockade on CFC and oscillatory synchrony between dorsal hippocampus (DH), prelimbic (PL) cortex, basolateral amygdala (BLA), and ventral hippocampus (VH), which sends hippocampal projections to PL and BLA.

Attitudes to the use of animals in biomedical research: Effects of stigma and selected research project summaries.

Three groups of participants (largely recruited from the UK) completed a survey to examine attitudes to the use of animals in biomedical research, after reading the lay (N = 182) or technical (N = 201) summary of a research project, or no summary (N = 215). They then completed a survey comprising the animal attitude (AAS), animal purpose (APQ), belief in animal mind (BAM) and empathy quotient (EQ) scales. The APQ was adapted to assess attitudes towards the use of animals for research into disorders selected to be perceived as controllable and so 'blameworthy' and potentially stigmatised (addiction and obesity) and 'psychological' (schizophrenia and addiction) versus 'physical' (cardiovascular disease and obesity), across selected species (rats, mice, fish pigs and monkeys).

Pharmacological modulation of Kv3 voltage-gated potassium channels regulates fear discrimination and expression in a response-dependent manner.

Various psychiatric diseases are characterized by aberrant cognition and emotional regulation. This includes inappropriately attributing affective salience to innocuous cues, which can be investigated using translationally relevant preclinical models of fear discrimination. Activity in the underpinning corticolimbic circuitry is governed by parvalbumin-expressing GABAergic interneurons, which also regulate fear discrimination.

Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats.

Endocannabinoid transmission is emerging as a target for treating anxiety-related disorders, given its regulation of fear extinction. Boosting anandamide levels via inhibition of its metabolism by fatty acid amide hydrolase (FAAH) can enhance extinction, whereas inhibiting monoacylglycerol lipase (MAGL) to elevate 2-arachidonoylglycerol levels can impair extinction. However, whether endocannabinoids regulate fear relapse over time or extinction resistance remains unclear.

Camellia sinensis solvent extract, epigallocatechin gallate and caffeine confer trophocidal and cysticidal effects against Acanthamoeba castellanii.

We examined the anti-acanthamoebic efficacy of green tea Camellia sinensis solvent extract (SE) or its chemical constituents against Acanthamoeba castellanii by using anti-trophozoite, anti-encystation, and anti-excystation assays. C. sinensis SE (625-5000 µg/mL) inhibited trophozoite replication within 24-72 h.

URB597 induces subtle changes to aggression in adult Lister Hooded rats.

The endocannabinoid system has been implicated in both social and cognitive processing. The endocannabinoid metabolism inhibitor, URB597, dose-dependently improves non-social memory in adult Wistar and Sprague Dawley rats, whereas its effect on social interaction (SI) is affected by both rat strain and drug dose. Lister Hooded rats consistently respond differently to drug treatment in general compared with albino strains.

Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance.

Cannabidiol, the main non-psychotropic constituent of cannabis, has potential as a treatment for anxiety-related disorders since it reduces learned fear expression and enhances fear extinction. The return of fear over time after successful extinction and stress-induced extinction resistance are potential barriers to the treatment of these disorders with extinction-based psychological therapy. In two experiments using rats subjected to auditory fear conditioning, we determined the effects of systemic cannabidiol treatment on (1) delayed extinction and later spontaneous fear recovery, and (2) extinction resistance caused by immediate extinction (the immediate extinction deficit (IED)).

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy.

() is an opportunistic protozoan that can cause brain infection and other serious health consequences in immuno-compromised individuals. This parasite has a remarkable ability to cross biological barriers and exploit the host cell microenvironment to support its own survival and growth. Recent advances in label-free spectroscopic imaging techniques have made it possible to study biological systems at a high spatial resolution.

Hippocampal Disinhibition Reduces Contextual and Elemental Fear Conditioning While Sparing the Acquisition of Latent Inhibition.

Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology.

In it together? The case for endocannabinoid-noradrenergic interactions in fear extinction.

Anxiety and trauma-related disorders, such as post-traumatic stress disorder (PTSD), are debilitating mental illnesses with great personal and socioeconomic costs. Examining memory formation and relevant behavioural responding associated with aversive stimuli may improve our understanding of the neurobiology underlying fear memory processing and PTSD treatment. The neurocircuitry underpinning learned fear and its inhibition through extinction is complex, involving synergistic interactions between different neurotransmitter systems in inter-connected brain areas.

Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders?

Coronavirus disease-19 (COVID-19)-related anxiety and post-traumatic stress symptoms (PTSS) or post-traumatic stress disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesize that cannabidiol (CBD), a chemical isolated from with reported anxiolytic properties, could be a therapeutic option for the treatment of COVID-19-related anxiety disorders. In the global over-the-counter CBD market, anxiety, stress, depression, and sleep disorders are consistently the top reasons people use CBD.

Structural, Functional, and Metabolic Alterations in Human Cerebrovascular Endothelial Cells during Infection and Amelioration by Verapamil In Vitro.

(), the causative agent of toxoplasmosis, is a frequent cause of brain infection. Despite its known ability to invade the brain, there is still a dire need to better understand the mechanisms by which this parasite interacts with and crosses the blood-brain barrier (BBB). The present study revealed structural and functional changes associated with infection and replication of within human brain microvascular endothelial cells (BMECs) in vitro.

In vitro activity of Camellia sinensis (green tea) against trophozoites and cysts of Acanthamoeba castellanii.

The effect of Camellia sinensis (green tea) on the growth of Acanthamoeba castellanii trophozoites was examined using a microplate based-Sulforhodamine B (SRB) assay. C. sinensis hot and cold brews at 75% and 100% concentrations significantly inhibited the growth of trophozoites.

Dopamine regulation of contextual fear and associated neural circuit function.

Learning to associate certain contexts with threat and adapting to changing environmental contingencies by learning that such contexts are no longer associated with threat are both crucial for survival. Research over the last few decades has made considerable progress in determining the brain areas involved in the encoding, retrieval and extinction of contextual fear. These studies have identified the hippocampus and amygdala, along with the prefrontal cortex and other inter-connected brain areas, as key players in contextual fear processing.

Sex differences in auditory fear discrimination are associated with altered medial prefrontal cortex function.

The increased prevalence of post-traumatic stress disorder (PTSD) that is observed in women may involve sex differences in learned fear inhibition and medial prefrontal cortex (mPFC) function. PTSD is characterized by fear overgeneralization involving impaired fear regulation by safety signals. We recently found that males show fear discrimination and females show fear generalization involving reduced safety signalling after extended fear discrimination training.

Improved functional connectivity network estimation for brain networks using multivariate partial coherence.

Objective: Graphical networks and network metrics are widely used to understand and characterise brain networks and brain function. These methods can be applied to a range of electrophysiological data including electroencephalography, local field potential and single unit recordings. Functional networks are often constructed using pair-wise correlation between variables.

The neurobiological basis of sex differences in learned fear and its inhibition.

Learning that certain cues or environments predict threat enhances survival by promoting appropriate fear and the resulting defensive responses. Adapting to changing stimulus contingencies by learning that such cues no longer predict threat, or distinguishing between these threat-related and other innocuous stimuli, also enhances survival by limiting fear responding in an appropriate manner to conserve resources. Importantly, a failure to inhibit fear in response to harmless stimuli is a feature of certain anxiety and trauma-related disorders, which are also associated with dysfunction of the neural circuitry underlying learned fear and its inhibition.

Cannabinoid Regulation of Fear and Anxiety: an Update.

Purpose Of Review: Anxiety- and trauma-related disorders are prevalent and debilitating mental illnesses associated with a significant socioeconomic burden. Current treatment approaches often have inadequate therapeutic responses, leading to symptom relapse. Here we review recent preclinical and clinical findings on the potential of cannabinoids as novel therapeutics for regulating fear and anxiety.

Dopamine D1-like receptors in the dorsomedial prefrontal cortex regulate contextual fear conditioning.

Rationale: Dopamine D1 receptor (D1R) signalling is involved in contextual fear conditioning. The D1R antagonist SCH23390 impairs the acquisition of contextual fear when administered systemically or infused locally into the dorsal hippocampus or basolateral amygdala.

Objectives: We determined if state dependency may account for the impairment in contextual fear conditioning caused by systemic SCH23390 administration.

Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry.

In this study, we measured the levels of elements in human brain microvascular endothelial cells (ECs) infected with T. gondii. ECs were infected with tachyzoites of the RH strain, and at 6, 24, and 48 hours post infection (hpi), the intracellular concentrations of elements were determined using a synchrotron-microfocus X-ray fluorescence microscopy (μ-XRF) system.

The Cumulative Complexity Model and Repeat Falls: A Quality Improvement Project.

Purpose Of Project: The purpose of this article is to demonstrate the effectiveness of the Cumulative Complexity Model as a framework to build an Excel tool and a Pareto tool that will enable inpatient case managers to predict the increased risk for and prevent repeat falls. The Excel tool is based on work explained in a previous article by and uses a macro to analyze the factors causing the repeat falls and then calculate the probability of it happening again. This enables the case manager to identify trends in how the patient is transitioning toward goals of care and identify problems before they become barriers to the smooth transition to other levels of care.

Adaptive spectral tracking for coherence estimation: the z-tracker.

Objective: A major challenge in non-stationary signal analysis is reliable estimation of correlation. Neurophysiological recordings can be many minutes in duration with data that exhibits correlation which changes over different time scales. Local smoothing can be used to estimate time-dependency, however, an effective framework needs to adjust levels of smoothing in response to changes in correlation.

WITHDRAWN: Drugs for preventing postoperative nausea and vomiting.

Background: Drugs can prevent postoperative nausea and vomiting, but their relative efficacies and side effects have not been compared within one systematic review.

Objectives: The objective of this review was to assess the prevention of postoperative nausea and vomiting by drugs and the development of any side effects.

Search Methods: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966 to May 2004), EMBASE (January 1985 to May 2004), CINAHL (1982 to May 2004), AMED (1985 to May 2004), SIGLE (to May 2004), ISI WOS (to May 2004), LILAC (to May 2004) and INGENTA bibliographies.