Preventive and Therapeutic Effects of Intracerebroventricular Administration of Maresin-1 on Lipopolysaccharide-Induced Depression-Like Behaviors in Mice.

Enhanced inflammatory and immune responses have been observed in patients with major depressive disorder, pointing to anti-inflammatory substances as potential seeds for developing novel antidepressants. Omega-3 polyunsaturated fatty acid metabolites, such as resolvin D and E series, maresins, and protectins (collectively known as specialized pro-resolving mediators) demonstrate anti-inflammatory effects. This study examined the antidepressant-like effects of maresin-1 (MaR1) on lipopolysaccharide (LPS)-induced depression-like behaviors in mice.

Activation of ventral pallidum-projecting neurons in the nucleus accumbens via 5-HT receptor stimulation regulates motivation for wheel running in male mice.

Rodents have a strong motivation for wheel running; however, the neural mechanisms that regulate their motivation remain unknown. We investigated the possible involvement of serotonin (5-HT) systems in regulating motivation for wheel running in male mice. Systemic administration of a 5-HT receptor antagonist (WAY100635) increased the number of wheel rotations, whereas administration of a 5-HT or 5-HT receptor antagonist (volinanserin or SB242084, respectively) decreased it.

Neohesperidin exerts antidepressant-like effect via the mechanistic target of rapamycin complex 1 in the medial prefrontal cortex in male mice.

Neohesperidin, a citrus flavonoid, shows potential for activating the mechanistic target of rapamycin complex 1 (mTORC1). Here, the antidepressant-like effect of neohesperidin was examined in male ICR mice (naïve mice and mice treated repeatedly with prednisolone, a synthetic glucocorticoid, which induces depression-like behavior). Oral neohesperidin administration exerted an antidepressant-like effect in the forced swim test 1 h post-treatment, in naïve mice; this effect was no longer observed at 24 h.

[Resolvin E1 as a potential lead for the treatment of depression].

Typical monoamine-based antidepressants have significant limitations, including a time lag for therapeutic response and low efficacy (more than one-third of depressed patients fail to respond to multiple antidepressant medications and are considered treatment-resistant). Conversely, ketamine, an N-methyl-D-aspartate receptor antagonist, exhibits rapid and sustained antidepressant actions in patients with treatment-resistant depression. However, clinical use of ketamine is limited due to its serious side effects.

Role of medial prefrontal cortex voltage-dependent potassium 4.3 channels in nicotine-induced enhancement of object recognition memory in male mice.

Nicotine has been shown to enhance object recognition memory in the novel object recognition (NOR) test by activating excitatory neurons in the medial prefrontal cortex (mPFC). However, the exact neuronal mechanisms underlying the nicotine-induced activation of mPFC neurons and the resultant memory enhancement remain poorly understood. To address this issue, we performed brain-slice electrophysiology and the NOR test in male C57BL/6J mice.

Neuron-specific deletion of VEGF or its receptor Flk-1 occludes the antidepressant-like effects of desipramine and fluoxetine in mice.

Vascular endothelial growth factor (VEGF) signaling is known to be involved in the antidepressant-like effects of conventional antidepressants, such as desipramine (DMI), a tricyclic antidepressant, and fluoxetine (FLX), a selective serotonin reuptake inhibitor; however, the precise role of neuronal VEGF signaling in mediating these effects remains unclear. Using mice with excitatory neuron-specific deletion of VEGF and its receptor, fetal liver kinase 1 (Flk-1) in the forebrain, we examined the effects of forebrain excitatory neuron-specific deletion of VEGF or Flk-1 on the antidepressant-like effects of repeated DMI and chronic FLX administration in the forced swim test (FST). Repeated intraperitoneal (i.

Social defeat stress enhances the rewarding effects of cocaine through α adrenoceptors in the medial prefrontal cortex of mice.

Various stressors potentiate the rewarding effects of cocaine and contribute to cocaine cravings. However, it remains unclear whether psychosocial stress enhances the rewarding effects of cocaine. Accordingly, this study employed a cocaine-conditioned place preference (CPP) paradigm combined with social defeat (SD) exposure to investigate the effects of acute SD stress on cocaine reward in male mice.

Antidepressant-like effects of tomatidine and tomatine, steroidal alkaloids from unripe tomatoes, via activation of mTORC1 in the medial prefrontal cortex in lipopolysaccharide-induced depression model mice.

Ketamine, an -methyl-D-aspartate receptor antagonist, produces rapid antidepressant effects in patients with treatment-resistant depression. However, owing to the undesirable adverse effects of ketamine, there is an urgent need for developing safer and more effective prophylactic and therapeutic interventions for depression. Preclinical studies have demonstrated that activation of the mechanistic target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex (mPFC) mediates the rapid antidepressant effects of ketamine.

[Elucidation of the Mechanisms Underlying the Rapid Antidepressant Actions of Ketamine and Search for Possible Candidates for Novel Rapid-acting Antidepressants].

Ketamine, an N-methyl-D-aspartate receptor antagonist, elicits swift antidepressant effects even in subjects with treatment-resistant depression. Nonetheless, owing to the serious adverse effects associated with ketamine, including psychotomimetic effects, the development of safer rapid-acting antidepressants is imperative. The elucidation of the mechanisms underlying the antidepressant effects of ketamine will facilitate the advancement of these alternative treatments.

Varenicline enhances recognition memory via α7 nicotinic acetylcholine receptors in the medial prefrontal cortex in male mice.

Previous studies postulated that chronic administration of varenicline, a partial and full agonist at α4β2 and α7 nicotinic acetylcholine receptors (nAChRs), respectively, enhances recognition memory. However, whether its acute administration is effective, on which brain region(s) it acts, and in what signaling it is involved, remain unknown. To address these issues, we conducted a novel object recognition test using male C57BL/6J mice, focusing on the medial prefrontal cortex (mPFC), a brain region associated with nicotine-induced enhancement of recognition memory.

Noradrenergic stimulation of α adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice.

Stress is one of the critical facilitators for seizure induction in patients with epilepsy. However, the neural mechanisms underlying this facilitation remain poorly understood. Here, we investigated whether noradrenaline (NA) transmission enhanced by stress exposure facilitates the induction of medial prefrontal cortex (mPFC)-originated seizures.

Role of 5-HT receptors in the basolateral amygdala on 3,4-methylenedioxymethamphetamine-induced prosocial effects in mice.

3,4-methylenedioxymethamphetamine (MDMA), a recreational drug, induces euphoric sensations and psychosocial effects, such as increased sociability and empathy. Serotonin, also called 5-hydroxytryptamine (5-HT), is a neurotransmitter that has been associated with MDMA-induced prosocial effects. However, the detailed neural mechanisms remain elusive.

Intranasal Administration of Resolvin E1 Produces Antidepressant-Like Effects via BDNF/VEGF-mTORC1 Signaling in the Medial Prefrontal Cortex.

Intracerebroventricular infusion of resolvin E1 (RvE1), a bioactive metabolite derived from eicosapentaenoic acid, exerts antidepressant-like effects in a mouse model of lipopolysaccharide (LPS)-induced depression; these effects are blocked by systemic injection of rapamycin, a mechanistic target of rapamycin complex 1 (mTORC1) inhibitor. Additionally, local infusion of RvE1 into the medial prefrontal cortex (mPFC) or dorsal hippocampal dentate gyrus (DG) produces antidepressant-like effects. To evaluate the potential of RvE1 for clinical use, the present study examined whether treatment with RvE1 via intranasal (i.

Role of neurotrophic and growth factors in the rapid and sustained antidepressant actions of ketamine.

The neurotrophic hypothesis of depression proposes that reduced levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) contribute to neuronal atrophy or loss in the prefrontal cortex (PFC) and hippocampus and impaired hippocampal adult neurogenesis, which are associated with depressive symptoms. Chronic, but acute, treatment with typical monoaminergic antidepressants can at least partially reverse these deficits, in part via induction of BDNF and/or VEGF expression, consistent with their delayed onset of action. Ketamine, an N-methyl-d-aspartate receptor antagonist, exerts rapid and sustained antidepressant effects.

Resolution of depression: antidepressant actions of resolvins.

Major depressive disorder, one of the most widespread mental illnesses, brings about enormous individual and socioeconomic consequences. Conventional monoaminergic antidepressants require weeks to months to produce a therapeutic response, and approximately one-third of the patients fail to respond to these drugs and are considered treatment-resistant. Although recent studies have demonstrated that ketamine, an N-methyl-D-aspartate receptor antagonist, produces rapid antidepressant effects in treatment-resistant patients, it also has undesirable side effects.

A spatiotemporal increase of neuronal activity accompanies the motivational effect of wheel running in mice.

Spatiotemporal patterns of neuronal activity underlying the motivational effect of rotating running wheels (RWs) in rodents remain largely undetermined. Here, we investigated changes of neuronal activity among brain regions associated with motivation across different intensities of motivation for RWs in mice. Daily exposure to RWs gradually increased rotation number, then became stable after approximately 3 weeks.

IGF-1 release in the medial prefrontal cortex mediates the rapid and sustained antidepressant-like actions of ketamine.

Ketamine, an N-methyl-D-aspartate receptor antagonist, exerts rapid and sustained antidepressant actions. Preclinical studies demonstrated that the release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor in the medial prefrontal cortex (mPFC) is essential for the antidepressant-like effects of ketamine. However, the role of other neurotrophic factors in the antidepressant-like effects of ketamine has not been fully investigated.

The antidepressant-like effect of resolvin E1 in repeated prednisolone-induced depression model mice.

Resolvin E1 (RvE1) is an anti-inflammatory lipid mediator derived from eicosapentaenoic acid. We previously demonstrated that intracerebroventricular (i.c.

Resolvin E1 Attenuates Chronic Pain-Induced Depression-Like Behavior in Mice: Possible Involvement of Chemerin Receptor ChemR23.

The antidepressant effect of eicosapentaenoic acid-derived bioactive lipid, resolvin E1 (RvE1), was examined in a murine model of chronic pain-induced depression using a tail suspension test. Because RvE1 reportedly possesses agonistic activity on a chemerin receptor ChemR23, we also examined the antidepressant effect of chemerin. Two weeks after surgery for unilateral spared nerve injury to prepare neuropathic pain model mice, immobility time was measured in a tail suspension test.

Nicotine enhances object recognition memory through inhibition of voltage-dependent potassium 7 channels in the medial prefrontal cortex of mice.

Nicotine administration enhances object recognition memory. However, target brain regions and cellular mechanisms underlying the nicotine effects remain unclear. In mice, the novel object recognition test revealed that systemic nicotine administration before training enhanced object recognition memory.

Resolvins as potential candidates for the treatment of major depressive disorder.

In contrast with the delayed onset of therapeutic responses and relatively low efficacy of currently available monoamine-based antidepressants, a single subanesthetic dose of ketamine, an N-methyl-D-aspartate receptor antagonist, produces rapid and sustained antidepressant actions even in patients with treatment-resistant depression. However, since the clinical use of ketamine as an antidepressant is limited owing to its adverse effects, such as psychotomimetic/dissociative effects and abuse potential, there is an unmet need for novel rapid-acting antidepressants with fewer side effects. Preclinical studies have revealed that the antidepressant actions of ketamine are mediated via the release of brain-derived neurotrophic factor and vascular endothelial growth factor, with the subsequent activation of mechanistic target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex.

Resolvin D2 attenuates chronic pain-induced depression-like behavior in mice.

Aim: We previously demonstrated that intracerebroventricular injection of resolvin D2 (RvD2), a bioactive lipid mediator derived from docosahexaenoic acid, ameliorated depression-like behavior in lipopolysaccharide-induced and chronic mild stress-induced mouse models of depression. In the present study, we examined the antidepressant effect of RvD2 on chronic pain-induced depression-like behavior.

Methods: To prepare the neuropathic pain model, mice were subjected to surgery for unilateral spared nerve injury.

Nicotine Enhances Object Recognition Memory via Stimulating α4β2 and α7 Nicotinic Acetylcholine Receptors in the Medial Prefrontal Cortex of Mice.

Nicotine has been known to enhance recognition memory in various species. However, the brain region where nicotine acts and exerts its effect remains unclear. Since the medial prefrontal cortex (mPFC) is associated with memory, we examined the role of the mPFC in nicotine-induced enhancement of recognition memory using the novel object recognition test in male C57BL/6J mice.

Nicotine Enhances Firing Activity of Layer 5 Pyramidal Neurons in the Medial Prefrontal Cortex through Inhibition of Kv7 Channels.

Nicotine enhances attention, working memory and recognition. One of the brain regions associated with these effects of nicotine is the medial prefrontal cortex (mPFC). However, cellular mechanisms that induce the enhancing effects of nicotine remain unclear.

Role of 5-HT receptor-mediated serotonergic transmission in the medial prefrontal cortex in acute restraint stress-induced augmentation of rewarding memory of cocaine in mice.

Stress enhances cocaine craving. We recently reported that acute restraint stress increases cocaine conditioned place preference (CPP) in mice; however, the underlying mechanisms remain unclear. This study aimed to examine the role of serotonergic transmission in the medial prefrontal cortex (mPFC) in cocaine CPP enhancement by acute restraint stress, which increases extracellular serotonin (5-HT) levels in the mPFC.