Resolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23.

Rationale: Resolvins are bioactive lipid mediators that are generated from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). We recently demonstrated that the DHA-derived resolvins D1 and D2 exert antidepressant effects. However, whether the EPA-derived resolvins E1 (RvE1) and E2 (RvE2) produce antidepressant effects is not clear.

Rapid and sustained antidepressant effects of resolvin D1 and D2 in a chronic unpredictable stress model.

Resolvin D1 (RvD1) and D2 (RvD2) are lipid mediators that are derived from docosahexaenoic acid. We recently demonstrated that intracerebroventricular (i.c.

Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors Through the mTORC1 Signaling Pathway.

Background: Resolvin D1 and D2 are bioactive lipid mediators that are generated from docosahexaenoic acid. Although recent preclinical studies suggest that these compounds have antidepressant effects, their mechanisms of action remain unclear.

Methods: We investigated mechanisms underlying the antidepressant effects of resolvin D1 and resolvin D2 in lipopolysaccharide (0.

Amelioration of the reduced antinociceptive effect of morphine in the unpredictable chronic mild stress model mice by noradrenalin but not serotonin reuptake inhibitors.

Background: Although alterations in not only the pain sensitivity but also the analgesic effects of opioids have been reported under conditions of stress, the influence of unpredictable chronic mild stress (UCMS) on the antinociceptive effects of opioid analgesics remains to be fully investigated. The present study examined the influence of UCMS on the thermal pain sensitivity and antinociceptive effects of two opioid analgesics, morphine (an agonist of opioid receptors) and tramadol (an agonist of μ-opioid receptor and an inhibitor of both noradrenaline and serotonin transporters). We also examined the effects of pretreatment with maprotiline (a noradrenaline reuptake inhibitor) and escitalopram (a serotonin reuptake inhibitor) on the antinociceptive action of morphine in mice under an UCMS condition.

(-)-Pentazocine induces visceral chemical antinociception, but not thermal, mechanical, or somatic chemical antinociception, in μ-opioid receptor knockout mice.

Background: (-)-Pentazocine has been hypothesized to induce analgesia via the κ-opioid (KOP) receptor, although the involvement of other opioid receptor subtypes in the effects of pentazocine remains unknown. In this study, we investigated the role of the μ-opioid (MOP) receptor in thermal, mechanical, and chemical antinociception induced by (-)-pentazocine using MOP receptor knockout (MOP-KO) mice.

Results: (-)-Pentazocine-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice.

Roles of β- and α2-adrenoceptors within the central nucleus of the amygdala in the visceral pain-induced aversion in rats.

We investigated the roles of β- and α(2)-adrenoceptors within the central nucleus of the amygdala (CeA) in the negative affective and sensory components of visceral pain in rats. We observed a dose-dependent reduction of intraperitoneal acetic acid-induced conditioned place aversion by bilateral injections of timolol, a β-adrenoceptor antagonist, or clonidine, an α(2)-adrenoceptor agonist, without reducing writhing behaviors. These data suggest a pivotal role of intra-CeA adrenoceptors in the negative affective, but not sensory, component of visceral pain.

Reciprocal regulation of ATPgammaS-induced monocyte chemoattractant protein-1 production by ERK and p38 MAP kinases in rat corticostriatal slice cultures.

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a well-defined chemokine implicated in the pathology of various neurodegenerative diseases and brain injuries, such as Alzheimer's disease, multiple sclerosis, stroke, and traumatic injury. We investigated the effect of the activation of P2 purinoceptors on MCP-1 production in rat corticostriatal slice cultures. Treatment with adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), a hydrolysis-resistant adenosine triphosphate (ATP) analog, induced MCP-1 production in astrocytes.

Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in mu-opioid receptor knockout mice.

Butorphanol is hypothesized to induce analgesia via opioid pathways, although the precise mechanisms for its effects remain unknown. In this study, we investigated the role of the mu-opioid receptor (MOP) in thermal, mechanical, and visceral chemical antinociception induced by butorphanol using MOP knockout (KO) mice. Butorphanol-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice.

Inhibition of glutamatergic transmission by morphine in the basolateral amygdaloid nucleus reduces pain-induced aversion.

We examined the role of glutamatergic transmission within the basolateral amygdaloid nucleus (BLA) in pain-induced aversion using a conditioned place paradigm and an in vivo microdialysis technique in rats. Microinjection of MK-801 (1 or 10 nmol/side) into the bilateral BLA 5 min before intraplantar injection of formalin dose-dependently attenuated formalin-induced conditioned place aversion (F-CPA) without affecting nociceptive behaviors, such as lifting, licking, and biting. On the contrary, microinjection of neither CNQX (30 nmol/side) nor AP-3 (30 nmol/side) showed any significant effect on F-CPA.

Characterization of the tritium-labeled analog of L-threo-beta-benzyloxyaspartate binding to glutamate transporters.

L-Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Termination of glutamate receptor activation and maintenance of low extracellular glutamate concentrations are primarily achieved by glutamate transporters (excitatory amino acid transporters 1-5, EAATs1-5) located on both the nerve endings and the surrounding glial cells. To identify the physiological roles of each subtype, subtype-selective EAAT ligands are required.

Inhibitory role of supraspinal P2X3/P2X2/3 subtypes on nociception in rats.

Extracellular ATP is known to mediate synaptic transmission as a neurotransmitter or a neuromodulator via ionotropic P2X and metabotropic P2Y receptors. Several lines of evidence have suggested that ATP facilitates pain transmission at peripheral and spinal sites via the P2X receptors, in which the P2X3 subtype is considered as an important candidate for the effect. Conversely, we previously found that the activation of supraspinal P2X receptors evoked antinociception.

Brain cytokines and chemokines: roles in ischemic injury and pain.

Cytokines and chemokines were originally identified as essential mediators for inflammatory and immune responses. Enhanced production and release of cytokines/chemokines are observed also in the central nervous system (CNS) under diverse pathological conditions. There is growing evidence showing that brain cytokines/chemokines play crucial roles in the neuro-glio-vascular interaction underlying the pathology of various brain disorders and therefore are potential targets for development of novel and effective therapeutics for CNS diseases.

Facilitative effect of a glutamate transporter inhibitor (2S,3S)-3-{3-[4-(trifluoromethyl)benzoylamino]benzyloxy}aspartate on the expression of methamphetamine-induced behavioral sensitization in rats.

We examined the effects of a potent glutamate transporter inhibitor, (2S,3S)-3-{3-[4-(trifluoromethyl)benzoylamino]benzyloxy}aspartate (TFB-TBOA), on the expression of methamphetamine-induced behavioral sensitization in rats. Rats were intraperitoneally treated with 2 mg/kg methamphetamine for 5 days and then challenged with 1 mg/kg methamphetamine. Intracerebroventricular administration of TFB-TBOA (0.

Gene transfer of GLT-1, a glutamate transporter, into the nucleus accumbens shell attenuates methamphetamine- and morphine-induced conditioned place preference in rats.

Several lines of evidence have suggested that the glutamatergic system in the nucleus accumbens (NAc) plays an important role in the conditioned rewarding effect of drugs of abuse. In addition, it is recognized that extracellular glutamate is rapidly removed from the synaptic cleft by Na+-dependent glutamate transporters in neurons and glial cells, thereby maintaining physiological levels of glutamate. We previously reported that activation of glutamate uptake by a glutamate transporter activator attenuated the acquisition of conditioned place preference induced by methamphetamine and morphine in mice.

Role of chemokines in ischemic neuronal stress.

Chemokines constitute a large family of structurally related small cytokines originally identified as the factors regulating the migration of leukocytes in inflammatory and immune responses. Enhanced production and release of chemokines are observed also in the central nervous system under diverse neuronal stresses including ischemia, axonal injury, and neurotoxic substances such as an Abeta-peptide. There is growing evidence that brain chemokines play crucial roles in the neuro-glio-vascular interaction underlying the pathology of various brain disorders.

Effect of MS-153, a glutamate transporter activator, on the conditioned rewarding effects of morphine, methamphetamine and cocaine in mice.

There is a body of evidence implying the involvement of the glutamatergic system in the conditioned rewarding effects of drugs of abuse. It is recognized that the release of extracellular glutamate from nerve terminals is counterbalanced by the functions of neuronal and glial glutamate transporters. In the present study, we investigated the effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), a glutamate transporter activator, on the induction of the conditioned place preference to morphine, methamphetamine and cocaine in mice.

Involvement of glial glutamate transporters in morphine dependence.

There are several lines of evidence implying the involvement of the central glutamatergic system in morphine dependence. Extracellular glutamate released from nerve terminals is counterbalanced by glutamate transporters in neurons (EAAC1 and EAAT4) and glial cells (GLT-1 and GLAST), thereby modulating the glutamatergic system and protecting neurons from an excitotoxic action of glutamate. Here we show that a glial glutamate transporter GLT-1 could be involved in physical and psychological morphine dependence.

Buprenorphine antinociception is abolished, but naloxone-sensitive reward is retained, in mu-opioid receptor knockout mice.

Buprenorphine is a relatively nonselective opioid receptor partial agonist that is used in the management of both pain and addiction. To improve understanding of the opioid receptor subtypes important for buprenorphine effects, we now report the results of our investigation on the roles of mu-, delta-, and kappa-opioid receptors in antinociceptive responses and place preferences induced by buprenorphine. Buprenorphine antinociception, assessed by hot-plate and tail-flick tests, was significantly reduced in heterozygous mu-opioid receptor knockout (MOR-KO) mice and abolished in homozygous MOR-KO mice.

Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain.

Chemokines are a family of peptides originally identified as the factors regulating the migration of leukocytes in inflammatory and immune responses. Recently, they have been shown to be produced in the central and peripheral nervous systems under various pathological conditions and act on neuronal and glial cells. In this study, we examined the production of monocyte chemoattractant protein-1 (MCP-1), a well-characterized chemokine, in dorsal root ganglia (DRG) in a rat model of neuropathic pain.

Involvement of locus coeruleus noradrenergic neurons in supraspinal antinociception by alpha,beta-methylene-ATP in rats.

We reported previously that intracerebroventricular (i.c.v.

Facilitation of morphine withdrawal symptoms and morphine-induced conditioned place preference by a glutamate transporter inhibitor DL-threo-beta-benzyloxyaspartate in rats.

There is a body of evidence implying the involvement of the central glutamatergic system in morphine dependence. In this study, we examined the effect of intracerebroventricular (i.c.

Effect of gene transfer of GLT-1, a glutamate transporter, into the locus coeruleus by recombinant adenoviruses on morphine physical dependence in rats.

There is a body of evidence implying the involvement of the central glutamatergic system in morphine dependence. We previously reported changes in the mRNA expression of a glial glutamate transporter GLT-1 in some brain regions of morphine-dependent and naloxone-precipitated withdrawal rats, and inhibition of morphine physical dependence by a glutamate transporter activator in mice. These findings support the possibility that glutamate transporters such as GLT-1 are involved in morphine dependence.