Inhibition of STAT-mediated cytokine responses to chemically-induced colitis prevents inflammation-associated neurobehavioral impairments.

Depression can be associated with chronic systemic inflammation, and production of peripheral proinflammatory cytokines and upregulation of the kynurenine pathway have been implicated in pathogenesis of depression. However, the mechanistic bases for these comorbidities are not yet well understood. As tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), which convert tryptophan to kynurenine, are rate-limiting enzymes of the kynurenine pathway, we screened TDO or IDO inhibitors for effects on the production of proinflammatory cytokines in a mouse macrophage cell line.

Dysregulation of dopamine neurotransmission in the nucleus accumbens in immobilization-induced hypersensitivity.

Cast immobilization causes sensory hypersensitivity, which is also a symptom of neuropathic pain and chronic pain. However, the mechanisms underlying immobilization-induced hypersensitivity remain unclear. The present study investigated the role of dopamine neurotransmission in the nucleus accumbens shell (NAcSh) of rats with cast immobilization-induced mechanical hypersensitivity using microdialysis.

The herbal medicines Inchinkoto and Saireito improved hepatic fibrosis via aquaporin 9 in the liver of a rat bile duct ligation model.

Objective: To determine if the administration of the Japanese herbal medicines Inchinkoto (ICKT) and Saireito (SRT) ameliorate hepatic fibrosis and derangement of hepatocyte aquaporins (AQPs) following bile duct ligation (BDL) in a rat model of obstructive cholestasis.

Materials And Methods: Five groups of Wistar rats were used, and the groups included sham surgery (Sham group), BDL with no treatment (NT group), BDL plus ICKT (ICKT group), BDL plus SRT (SRT group), and BDL plus ICKT and SRT (SRT/ICKT group). Each herbal medicine was administered at 1 g/kg/day on the first postoperative day.

Adolescent psychosocial stress enhances sensitization to cocaine exposure in genetically vulnerable mice.

Development of drug addictive behaviors is modulated by both genetic and environmental risk factors. However, the molecular mechanisms remain unknown. To address the role of adolescent stress in the development of drug addiction, we combined a transgenic mouse model in which a putative dominant-negative form of DISC1 under expressional control of the prion protein promoter is used as a genetic risk factor and adolescent social isolation stress as a gene-environmental interaction (GXE).

Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant actions of a selective serotonin reuptake inhibitor, fluoxetine.

Depression is a leading cause of disability. Current pharmacological treatment of depression is insufficient, and development of improved treatments especially for treatment-resistant depression is desired. Understanding the neurobiology of antidepressant actions may lead to development of improved therapeutic approaches.