Therapeutic-like activity of cannabidiolic acid methyl ester in the MK-801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin-1A receptors.

Schizophrenia is a psychotic disorder with an increasing prevalence and incidence over the last two decades. The condition presents with a diverse array of positive, negative, and cognitive impairments. Conventional treatments often yield unsatisfactory outcomes, especially with negative symptoms.

Cross-sex cecal microbiota transfer alters depressive-like behaviours in mice.

Major depressive disorder (MDD) is a leading cause of non-fatal global disease burden, with females being two-fold more likely than males to be diagnosed with the disorder. Despite this sex-linked disparity of diagnosis, it is unclear what underlies the sex bias in MDD. Recent findings suggest a role for the gut in mediating affective disorders through the gut-brain-axis (GBA).

A short pre-conception bout of predation risk affects both children and grandchildren.

Traumatic events that affect physiology and behavior in the current generation may also impact future generations. We demonstrate that an ecologically realistic degree of predation risk prior to conception causes lasting changes in the first filial (F1) and second filial (F2) generations. We exposed male and female mice to a live rat (predator stress) or control (non-predator) condition for 5 min.

Antibiotic-induced socio-sexual behavioral deficits are reversed via cecal microbiota transplantation but not androgen treatment.

Recent evidence has demonstrated a sex-specific role of the gut microbiome on social behavior such as anxiety, possibly driven by a reciprocal relationship between the gut microbiome and gonadal hormones. For instance, gonadal hormones drive sex differences in gut microbiota composition, and certain gut bacteria can produce androgens from glucocorticoids. We thus asked whether the gut microbiome can influence androgen-dependent socio-sexual behaviors.

Putative pathological mechanisms of late-life depression and Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive impairment in cognition and memory. AD is accompanied by several neuropsychiatric symptoms, with depression being the most prominent. Although depression has long been known to be associated with AD, controversial findings from preclinical and clinical studies have obscured the precise nature of this association.

Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments.

Given that available antidepressant pharmacotherapies are not optimally effective, there is a need for alternative treatment options that are rooted in a comprehensive understanding of the illness's pathophysiology. Major depressive disorder (MDD) has been historically attributed to monoamine, i.e.

Antidepressant activity of pharmacological and genetic deactivation of the small-conductance calcium-activated potassium channel subtype-3.

Rationale: The voltage-insensitive, small-conductance calcium-activated potassium (SK) channel is a key regulator of neuronal depolarization and is implicated in the pathophysiology of depressive disorders.

Objective: We ascertained whether the SK channel is impaired in the chronic unpredictable stress (CUS) model and whether it can serve as a molecular target of antidepressant action.

Methods: We assessed the depressive-like behavioral phenotype of CUS-exposed rats and performed post-mortem SK channel binding and activity-dependent zif268 mRNA analyses on their brains.

Antidepressant action of transcranial direct current stimulation in olfactory bulbectomised adolescent rats.

Background: Antidepressant drugs in adolescent depression are sometimes mired by efficacy issues and paradoxical effects. Transcranial direct current stimulation (tDCS) could represent an alternative.

Aims/methods: We tested the antidepressant action of prefrontal tDCS and paroxetine (20 mg/kg, intraperitoneal) in olfactory bulbectomised (OBX) adolescent rats.

A Key Role for Prefrontocortical Small Conductance Calcium-Activated Potassium Channels in Stress Adaptation and Rapid Antidepressant Response.

The muscarinic acetylcholine receptor antagonist scopolamine elicits rapid antidepressant activity, but its underlying mechanism is not fully understood. In a chronic stress model, a single low-dose administration of scopolamine reversed depressive-like reactivity. This antidepressant-like effect was mediated via a muscarinic M1 receptor-SKC pathway because it was mimicked by intra-medial prefrontal cortex (intra-mPFC) infusions of scopolamine, of the M1 antagonist pirenzepine or of the SKC antagonist apamin, but not by the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine.

In Vivo Brain Sampling Using a Microextraction Probe Reveals Metabolic Changes in Rodents after Deep Brain Stimulation.

Brain metabolomics is an emerging field that complements the more traditional approaches of neuroscience. However, typical brain metabolomics workflows require that animals be sacrificed and tend to involve tedious sample preparation steps. Microdialysis, the standard technique to study brain metabolites in vivo, is encumbered by significant limitations in the analysis of hydrophobic metabolites, which are prone to adsorption losses on microdialysis equipment.

Rostrocaudal subregions of the ventral tegmental area are differentially impacted by chronic stress.

Rationale: The ventral tegmental area (VTA) is implicated in the pathophysiology of depression and addictive disorders and is subject to the detrimental effects of stress. Chronic stress may differentially alter the activity pattern of its different subregions along the rostrocaudal and dorsoventral axes, which may relate to the variable behavioral sensitivity to stress mediated by these subregions.

Objectives: Here, chronic stress-exposed rats were tested for depressive-like reactivity.

High frequency stimulation of the anterior vermis modulates behavioural response to chronic stress: involvement of the prefrontal cortex and dorsal raphe?

Some evidence suggests that the cerebellum modulates affect via connectivities with mood-regulating corticolimbic structures, such as the prefrontal cortex and monoamine nuclei. In rats exposed to chronic unpredictable stress (CUS), we examined the neuro-behavioural effects of high frequency stimulation and surgical ablation/disconnection of the cerebellar vermis. CUS reduced sucrose preference, increased novelty-induced feeding suppression and passive coping.

Evaluation of a novel radiotracer for positron emission tomography imaging of reactive oxygen species in the central nervous system.

Introduction: Few, if any, radiotracers are available for the in vivo imaging of reactive oxygen species (ROS) in the central nervous system. ROS play a critical role in normal cell processes such as signaling and homeostasis but overproduction of ROS is implicated in several disorders. We describe here the radiosynthesis and initial ex vivo and in vivo evaluation of [C]hydromethidine ([C]HM) as a radiotracer to image ROS using positron emission tomography (PET).

The fatty acid amide hydrolase inhibitor URB597 modulates serotonin-dependent emotional behaviour, and serotonin1A and serotonin2A/C activity in the hippocampus.

The fatty acid amide hydrolase (FAAH) inhibitor URB597 increases anandamide, resulting in antidepressant/anxiolytic-like activity, likely via CB1 receptor-mediated modulation of serotonin (5-HT) and norepinephrine (NE) neurotransmission. However, the relative importance of the 5-HT and NE systems in these effects and on effects of URB597 on postsynaptic 5-HT receptors remain to be determined. Using behavioural and electrophysiological approaches, we assessed the effects of acute-single and repeated URB597 treatment on responses predicting antidepressant/anxiolytic activity, and on hippocampal 5-HT1A and 5-HT2A/C receptor sensitivity.

Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats.

Chronic ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) improves depressive-like behaviour in rats via serotonergic and neurotrophic-related mechanisms. We hypothesise that, in addition to these substrates, DBS-induced increases in hippocampal neurogenesis may also be involved. Our results show that stress-induced behavioural deficits in the sucrose preference test, forced swim test, novelty-suppressed feeding test (NSFT) and elevated plus maze were countered by chronic vmPFC DBS.

Rapid anti-depressant and anxiolytic actions following dopamine D1-D2 receptor heteromer inactivation.

A role for the mesolimbic dopaminergic system in the pathophysiology of depression has become increasingly evident. Specifically, brain-derived neurotrophic factor (BDNF) has been shown to be elevated in the nucleus accumbens of depressed patients and to positively contribute to depression-like behaviour in rodents. The dopamine D1-D2 receptor heteromer exhibits significant expression in NAc and has also been shown to enhance BDNF expression and signalling in this region.

Melancholic-Like behaviors and circadian neurobiological abnormalities in melatonin MT1 receptor knockout mice.

Background: Melancholic depression, described also as endogenous depression, is a mood disorder with distinctive specific psychopathological features and biological homogeneity, including anhedonia, circadian variation of mood, psychomotor activation, weight loss, diurnal cortisol changes, and sleep disturbances. Although several hypotheses have been proposed, the etiology of this disorder is still unknown.

Methods: Behavioral, electrophysiological and biochemical approaches were used to characterize the emotional phenotype, serotonergic and noradrenergic electrical activity, and corticosterone in melatonin MT1 receptor knockout mice and their wild type counterparts, during both light and dark phases.

Father absence in the monogamous california mouse impairs social behavior and modifies dopamine and glutamate synapses in the medial prefrontal cortex.

The role of the father in psycho-affective development is indispensable. Yet, the neurobehavioral effects of paternal deprivation (PD) are poorly understood. Here, we examined the behavioral consequences of PD in the California mouse, a species displaying monogamous bonding and biparental care, and assessed its impact on dopamine (DA), serotonin (5-HT), and glutamate (GLU) transmission in the medial prefrontal cortex (mPFC).

Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects.

Chronic stressful life events are risk factors for developing major depression, the pathophysiology of which is strongly linked to impairments in serotonin (5-HT) neurotransmission. Exposure to chronic unpredictable stress (CUS) has been found to induce depressive-like behaviours, including passive behavioural coping and anhedonia in animal models, along with many other affective, cognitive, and behavioural symptoms. The heterogeneity of these symptoms represents the plurality of corticolimbic structures involved in mood regulation that are adversely affected in the disorder.

Novel insights into depression and antidepressants: a synergy between synaptogenesis and neurogenesis?

Major depressive disorder has been associated with manifold pathophysiological changes. These include metabolic abnormalities in discreet brain areas; modifications in the level of stress hormones, neurotransmitters, and neurotrophic factors; impaired spinogenesis and synaptogenesis in crucial brain areas, such as the prefrontal cortex and the hippocampus; and impaired neurogenesis in the hippocampus. Antidepressant therapy facilitates remission by reversing most of these disturbances, indicating that these dysfunctions may participate causally in depressive symptomatology.

Effect of delta-9-tetrahydrocannabinol on behavioral despair and on pre- and postsynaptic serotonergic transmission.

Preclinical and clinical studies suggest that direct and indirect cannabinoid agonists, including enhancers of endocannabinoids, engender stress-relieving, anxiolytic and antidepressant effects, mediated by central CB(1) receptors (CB(1)Rs). The effect of the main pharmacologically active principle in cannabis, (-)-trans-Δ(9)-tetrahydrocannabinol (delta-9-THC), on depressive behavior and on the serotonin (5-HT) system, which is implicated in the mechanism of action of antidepressants, has not been extensively clarified. Here, we showed that repeated (5 days), but not single (acute) intraperitoneal (ip) treatment with delta-9-THC (1mg/kg) exerts antidepressant-like properties in the rat forced swim test (FST).

Prefrontal cortical anandamide signaling coordinates coping responses to stress through a serotonergic pathway.

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.