and protect against decreased KCC2 expression induced by the lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice.

(KSS) and (KKT) have been traditionally prescribed for neuropsychiatric symptoms in Japan. However, the molecular mechanism of its effect is not elucidated enough. On the other hand, it has been reported that lipopolysaccharide derived from ( LPS) is involved not only in periodontal disease but also in the systemic diseases such as psychiatric disorders via neuroinflammation.

Therapeutic potential for KCC2-targeted neurological diseases.

Patients with neurological diseases, such as schizophrenia, tend to show low K-Cl co-transporter 2 (KCC2) levels in the brain. The cause of these diseases has been associated with stress and neuroinflammation. However, since the pathogenesis of these diseases is not yet fully investigated, drug therapy is still limited to symptomatic therapy.

Neuroprotective effect of oxytocin on cognitive dysfunction, DNA damage, and intracellular chloride disturbance in young mice after cranial irradiation.

Cranial radiation therapy (CRT) is an effective treatment for brain tumors; however, it also causes brain injuries. The pediatric brain is considered especially vulnerable compared to the adult brain; thus, brain injuries caused by CRT may severely affect their quality of life. In this study, we determined the neuroprotective effects of nasal oxytocin administration following cranial radiation in mice.

Are Histamine H Antagonists the Definitive Treatment for Acute Methamphetamine Intoxication?

Background: Methamphetamine (METH) is classified as a Schedule II stimulant drug under the United Nations Convention on Psychotropic Substances of 1971. METH and other amphetamine analogues (AMPHs) are powerful addictive drugs. Treatments are needed to treat the symptoms of METH addiction, chronic METH use, and acute METH overdose.

Metoprine, a histamine N-methyltransferase inhibitor, attenuates methamphetamine-induced hyperlocomotion via activation of histaminergic neurotransmission in mice.

Metoprine increases the content of histamine in brain by inhibiting histamine N-methyltransferase (HMT), a centrally acting histamine degrading enzyme. We present data demonstrating that pretreatment with metoprine attenuates the hyperlocomotive effects of METH in mice using a multi-configuration behavior apparatus designed to monitor four behavioral outcomes [horizontal locomotion, appetitive behavior (food access), and food and water intake]. Metoprine pretreatment itself induced hyperlocomotion in mice challenged with saline during the large part of light phase.

Elevated H2 O2 levels in trinitrobenzene sulfate-induced colitis rats contributes to visceral hyperalgesia through interaction with the transient receptor potential ankyrin 1 cation channel.

Background And Aim: Inflammatory bowel disease is associated with chronic abdominal pain. Transient receptor potential ankyrin 1 (TRPA1) is a well-known pain sensor expressed in primary sensory neurons. Recent studies indicate that reactive oxygen species such as hydrogen peroxide (H2 O2 ) may activate TRPA1.

Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine.

In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.

Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice.

We investigated whether pretreatment with the neurotransmitter/neuromodulator agmatine (decarboxylated L-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing.

The selective μ opioid receptor antagonist β-funaltrexamine attenuates methamphetamine-induced stereotypical biting in mice.

We investigated whether pretreatment with opioid receptor antagonists affected methamphetamine (METH)-induced stereotypy in mice. Pretreatment of male ICR mice with naloxone, a relatively non-selective opioid receptor antagonist, significantly attenuated the total incidence of METH-induced stereotypical behavior compared with saline vehicle-pretreated subjects. Furthermore, the distribution of METH-induced stereotypical behavior was affected by naloxone administration.

Straub tail reaction in mice treated with σ(1) receptor antagonist in combination with methamphetamine.

Straub tail reaction (STR) was observed in male ddY mice after simultaneous administration with BMY 14802 (a non-specific σ receptor antagonist) and methamphetamine (METH). The intensity and duration of STR depended on the dose of BMY 14802. The tail reaction was inhibited completely by (+)-SKF 10,047 (a putative σ(1) receptor agonist) and partially by PB 28 (a putative σ(2) receptor agonist).

Pretreatment with nomifensine or nomifensine analogue 4-phenyl-1,2,3,4-tetrahydroisoquinoline augments methamphetamine-induced stereotypical behavior in mice.

Nomifensine is a dopamine/norepinephrine reuptake inhibitor. Nomifensine and some of its structural analogues produce behavioral effects indicative of indirect dopaminergic agonist properties, such as hyperlocomotion. By contrast, the deaminated and demethylated nomifensine analogue 4-phenyl-1,2,3,4-tetrahydroisoquinoline (PTIQ) is reported to have amphetamine-antagonistic properties, as demonstrated by inhibition of methamphetamine (METH)-induced dopamine release in the nucleus accumbens and METH-induced hyperlocomotion in rats.

Histamine H3 receptor agonists decrease hypothalamic histamine levels and increase stereotypical biting in mice challenged with methamphetamine.

The effects of the histamine H(3) receptor agonists (R)-α-methylhistamine, imetit and immepip on methamphetamine (METH)-induced stereotypical behavior were examined in mice. The administration of METH (10 mg/kg, i.p.

Withdrawal from fixed-dose injection of methamphetamine decreases cerebral levels of 3-methoxy-4-hydroxyphenylglycol and induces the expression of anxiety-related behavior in mice.

A variety of drug treatment regimens have been proposed to model the dysphoric state observed during methamphetamine (METH) withdrawal in rats, but little has been established in experiments using mice. In male ICR mice, a fixed-dose injection regimen of METH (1.0 or 2.

Pretreatment with l-histidine produces a shift from methamphetamine-induced stereotypical biting to persistent locomotion in mice.

The administration of methamphetamine (METH; 10mg/kg, i.p.) to male ICR mice induced bizarre behaviors including persistent locomotion and stereotypical behaviors, which were classified into four categories: stereotypical head-bobbing, circling, sniffing, and biting.

Effect of acetaminophen, a cyclooxygenase inhibitor, on Morris water maze task performance in mice.

Although the mechanism of action of acetaminophen (AAP) is not fully understood, some studies suggest that AAP and phenacetin (PHE) are selective cyclooxygenase (COX)-3 inhibitors. To examine the participation of COX-3 in memory formation, water maze performance was studied in mice treated with AAP, PHE or other COX inhibitors. Mice received intraperitoneal injections of drugs immediately after each training session.

Effect of NC-1900, an active fragment analog of arginine vasopressin, and inhibitors of arachidonic acid metabolism on performance of a passive avoidance task in mice.

In this study, we investigated the effect of administration of inhibitors of each of the arachidonic acid metabolism pathways and the effect of co-administration of these inhibitors with NC-1900, a fragment analog of arginine vasopressin, on step-through passive avoidance task performance. All drugs were administered just after the acquisition trial in the passive avoidance task. Intracerebroventricular (i.

Hydrogen peroxide-induced thymidine incorporation into cultured rat astrocytes.

We characterized [methyl-(3)H]thymidine ([(3)H]thymidine) and [5-(3)H]uridine ([(3)H]uridine) incorporation into cultured astrocytes and neurons in the presence and absence of hydrogen peroxide (H2O2) in order to define the response to oxidative stress in the central nervous system. [(3)H]Thymidine incorporation into cultured astrocytes was remarkably decreased by N(6),2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP), a permeable analogue of cAMP, which induced a morphological change from the polygonal form (undifferentiated astrocytes) to the process-bearing one (differentiated astrocytes). H2O2 induced [(3)H]thymidine, but not [(3)H]uridine, incorporation into cultured astrocytes at only an early time from 24 h after DBcAMP treatment, although the absolute quantities of [(3)H]thymidine incorporation into astrocytes pretreated with DBcAMP were less than those into astrocytes pretreated without DBcAMP.

Glutamate antagonists attenuate the action of NC-1900, a vasopressin fragment analog, on passive avoidance task performance in mice.

To examine the relationship between glutamate receptors and the action of NC-1900 on a step-through passive avoidance (PA) task in mice, MK-801, an NMDA receptor blocker, and (S)-4-carboxyphenylglycine (4CPG), a group I metabotropic receptor antagonist, were administered intraventricularly (i.c.v.

Ameliorative and exacerbating effects of [pGlu(4),Cyt(6)]AVP((4-9)) on impairment of step-through passive avoidance task performance by group II metabotropic glutamate receptor-related drugs in mice.

To examine the effect of the arginine-vasopressin fragment, [pGlu(4),Cyt(6)]AVP((4-9)) (AVP4-9), on group II metabotropic glutamate receptor (mGluR2/3) agonist and antagonist induced impairment of passive avoidance (PA) task performance, AVP4-9 or phorbol 12-myristate 13-acetate (PMA) was administered in the presence of mGluR2/3-related drugs that induced the impairment of the step-through-type PA task performance. The PA task performance was evaluated in terms of the latency (the time that elapsed prior to entry into the dark compartment) at 24 h after the electrical stimulation. The subcutaneous injection of AVP4-9 at 1 mug/kg had the greatest facilitative effect on the performance, and the facilitative effect of AVP4-9 was inhibited by NPC-15437, a specific protein kinase C (PKC) inhibitor.

Facilitative effect of a novel AVP fragment analog, NC-1900, on memory retention and recall in mice.

In order to determine the mechanism of action of a new AVP(4-9) analog, NC-1900, on memory processes, memory retention and retrieval tests were conducted in a step-through passive avoidance (PA) task in mice. The administration of NC-1900 facilitated memory retention and retrieval in the PA task through vasopressin1A (V1A) receptors but not V2 receptors. The effect of NC-1900 on memory retention test performance appeared to be due to activation of the protein kinase C (PKC) signaling pathway via V1A receptors; however, the modulation of PKC was not essential for the facilitative effect of the new peptide in the retrieval test.

Effect of pretraining administration of NC-1900, a vasopressin fragment analog, on memory performance in non- or CO2-amnesic mice.

In the present study, we investigated the facilitative effect of NC-1900, a new arginine vasopressin (AVP(1-9)) fragment analog, on memory performance in eight-arm radial maze or passive avoidance (PA) tasks in nonamnesic and amnesic (PA tasks only) mice. In the radial maze, all injections (subcutaneous) were given daily 60 min before each trail. NC-1900 (1 ng/kg)-treated animals showed enhancement of performance, and AVP(4-9) (1 microg/kg), an AVP(1-9) fragment, had similar effects, although the effective dose was 1000-fold higher.

Effect of donepezil on group II mGlu receptor agonist- or antagonist-induced amnesia on passive avoidance in mice.

We examined the effect of the acetylcholinesterase (AChE) inhibitor, donepezil hydrocloride (DONP), on group II metabotropic glutamate (mGlu) receptor agonist- or antagonist-induced amnesia in the step-through passive avoidance task in male mice. DCG-IV, a group II mGlu receptor agonist, at dose of 50 ng and LY341495, a group II mGlu receptor antagonist, at dose of 300 ng, significantly attenuated the latency on the step-through task. The subcutaneous injection of DONP at dose of 1 mg/kg 1 hour before passive avoidance performance ameliorated the amnesia induced by DCG-IV and LY341495, whereas donepezil alone did not affect task latency.

Effects of estradiol and progesterone on radial maze performance in middle-aged female rats fed a low-calcium diet.

There is increasing evidence that ovarian steroids and calcium ions are involved in learning and memory. To examine the effect of ovarian steroids on learning and memory under a low-calcium condition, middle-aged female rats were fed either a low-calcium (0.02% Ca) or a normal-calcium (1.

Inhibitory effects of group II mGluR-related drugs on memory performance in mice.

The cAMP/protein kinase A signaling pathway is negatively modulated by group II metabotropic glutamate receptors (mGluRs), and the cross-talk that occurs between these receptors may modulate learning and memory. To examine the relationship among cAMP/PKA-signaling pathway activity, group II mGluRs, and learning and memory, mice were trained to perform a step-through-type passive avoidance task, and 10 min before each avoidance trial the following drugs were injected intracisternally (i.cist.

Effects of steroid hormones on (Na+, K+)-ATPase activity inhibition-induced amnesia on the step-through passive avoidance task in gonadectomized mice.

Inhibition of sodium-potassium adenosine 5'-triphosphatase ((Na(+), K(+))-ATPase) activity causes edema and cell death in the central nervous system, and impairment of learning and memory. Several sex steroid hormones have a protective effect against neuronal cell damage and the hypofunction of learning and memory. To examine the possible roles and mechanism of action of steroid hormones against amnesia induced by ouabain, an inhibitor of (Na(+), K(+))-ATPase, gonadectomized male mice were administrated ouabain (0.