Decreased sensitivity to antidepressant drugs in Wistar Hannover rats submitted to two animal models of depression.

The Wistar Hannover rat (WHR) is a strain commonly used for toxicity studies but rarely used in studies investigating depression neurobiology. In this study, we aimed to characterise the behavioural responses of WHR to acute and repeated antidepressant treatments upon exposure to the forced swim test (FST) or learned helplessness (LH) test. WHR were subjected to forced swimming pre-test and test with antidepressant administration (imipramine, fluoxetine, or escitalopram) at 0, 5 h and 23 h after pre-test.

CB1 Receptor Silencing Attenuates Ketamine-Induced Hyperlocomotion Without Compromising Its Antidepressant-Like Effects.

The antidepressant properties of ketamine have been extensively demonstrated in experimental and clinical settings. However, the psychotomimetic side effects still limit its wider use as an antidepressant. It was recently observed that endocannabinoids are inolved in ketamine induced reward properties.

Inducible Nitric Oxide Synthase Inhibition in the Medial Prefrontal Cortex Attenuates the Anxiogenic-Like Effect of Acute Restraint Stress CB Receptors.

Stress exposure can result in several proinflammatory alterations in the brain, including overexpression of the inducible isoform of nitric oxide synthase (iNOS) in the medial prefrontal cortex (mPFC). These changes may be involved in the development of many psychiatric conditions. However, it is unknown if iNOS in mPFC plays a significant role in stress-induced behavioral changes.

Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms.

Significant limitations with the currently available antidepressant treatment strategies have inspired research on finding new and more efficient drugs to treat depression. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa, and emerges in this regard as a promising compound. In 2010, we were the first laboratory to demonstrate that CBD is effective in animal models of predictive of antidepressant effect, a finding now confirmed by several other groups.

Nitric oxide signalling and antidepressant action revisited.

Studies about the pathogenesis of mood disorders have consistently shown that multiple factors, including genetic and environmental, play a crucial role on their development and neurobiology. Multiple pathological theories have been proposed, of which several ultimately affects or is a consequence of dysfunction in brain neuroplasticity and homeostatic mechanisms. However, current clinical available pharmacological intervention, which is predominantly monoamine-based, suffers from a partial and lacking response even after weeks of continuous treatment.

S-ketamine reduces marble burying behaviour: Involvement of ventromedial orbitofrontal cortex and AMPA receptors.

Previous clinical and pre-clinical studies suggest the involvement of ventromedial orbitofrontal cortex (vmOFC) and glutamatergic neurotransmission in obsessive-compulsive disorder (OCD). Ketamine, an NMDA glutamatergic receptor antagonist, has shown a rapid and long-lasting antidepressant effect, but its anti-compulsive effect has been scarcely investigated. The antidepressant effect of ketamine involves NMDA receptor blockade, AMPA receptor activation, increased serotonin (5-HT) release and attenuation of nitric oxide (NO) synthesis.

Attenuation of glutamatergic and nitrergic system contributes to the antidepressant-like effect induced by capsazepine in the forced swimming test.

The transient receptor potential vanilloid 1 (TRPV1) can modulate stress-related behaviours, thus representing an interesting target for new antidepressant drugs. TRPV1 can trigger glutamate release and nitric oxide synthesis in the brain, mechanisms also involved in the neurobiology of depression. However, it is not known if these mechanisms are involved in TRPV1-induced behavioural effects.

Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test.

Background: Cannabidiol is a non-psychotomimetic compound with antidepressant-like effects. However, the mechanisms and brain regions involved in cannabidiol effects are not yet completely understood. Brain-derived neurotrophic factor/tropomyosin-receptor kinase B/mammalian target of rapamycin (BDNF-TrkB-mTOR) signaling, especially in limbic structures, seems to play a central role in mediating the effects of antidepressant drugs.

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.

Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health. Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is a promising compound since it shows large-spectrum therapeutic potential in preclinical models and humans.

Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: involvement of nitric oxide.

Activation of purinergic receptors by ATP (P2R) modulates glutamate release and the activation of post-synaptic P2R is speculated to induce nitric oxide (NO) synthesis. Increased glutamatergic and nitrergic signaling have been involved in the neurobiology of stress-related psychiatric disorders such as anxiety and depression. Therefore, the aim of this study was to test the effects of two P2R antagonists (PPADS and iso-PPADS) in animals submitted to models predictive of antidepressant-, anxiolytic- and anticompulsive-like effects.