Increase in neuropeptide Y activity impairs social behaviour in association with glutamatergic dysregulation in diabetic mice.

Background And Purpose: Patients with diabetes mellitus are reported to show a raised prevalence of mental disorders, which may be reflected in impaired social interaction. However, the mechanisms underlying such impairment in diabetes are unknown.

Experimental Approach: The present study investigated whether social interaction is impaired in diabetic mice and whether central neuropeptide Y (NPY) and glutamatergic function are involved in such impairment.

Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia nigra contributes to Parkinson's disease-like motor dysfunction.

Ghrelin exerts a wide range of physiological actions throughout the body and appears to be a promising target for disease therapy. Endogenous ghrelin receptors (GHSRs) are present in extrahypothalamic sites including the substantia nigra pars compacta (SNc), which is related to phenotypic dysregulation or frank degeneration in Parkinson's disease (PD). Here we found a dramatic decrease in the expression of GHSR in PD-specific induced pluripotent stem cell (iPSC)-derived dopaminergic (DAnergic) neurons generated from patients carrying parkin gene (PARK2) mutations compared to those from healthy controls.

Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal dopaminergic cells or the inhibition of striatal dopamine receptors.

Ghrelin plays roles in a wide range of central functions by activating the growth hormone secretagogue receptor (GHSR). This receptor has recently been found in the substantia nigra (SN) to control dopamine (DA)-related physiological functions. The dysregulation of DA neurons in the SN pars compacta (SNc) and the consequent depletion of striatal DA are known to underlie the motor deficits observed in Parkinson's disease (PD).

Orthographic Reading Deficits in Dyslexic Japanese Children: Examining the Transposed-Letter Effect in the Color-Word Stroop Paradigm.

In orthographic reading, the transposed-letter effect (TLE) is the perception of a transposed-letter position word such as "cholocate" as the correct word "chocolate." Although previous studies on dyslexic children using alphabetic languages have reported such orthographic reading deficits, the extent of orthographic reading impairment in dyslexic Japanese children has remained unknown. This study examined the TLE in dyslexic Japanese children using the color-word Stroop paradigm comprising congruent and incongruent Japanese hiragana words with correct and transposed-letter positions.

Changes in the expression of IL-6-Mediated MicroRNAs in the dorsal root ganglion under neuropathic pain in mice.

A multiplex analysis for profiling the expression of candidate microRNAs (miRNAs), which are small noncoding RNAs that function as key post-transcriptional regulators, may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we performed a miRNA array analysis using tissues of the dorsal root ganglion (DRG), a primary site for pain processing, obtained from mice with partial sciatic nerve ligation. Among 1135 total miRNAs, 26 miRNAs showed up-regulation (more than 2-fold change) and only 4 miRNAs showed down-regulation (less than 0.

Differences in the morphine-induced inhibition of small and large intestinal transit: Involvement of central and peripheral μ-opioid receptors in mice.

Constipation is the most common side effect of morphine. Morphine acts centrally and on peripheral sites within the enteric nervous system. There are a few comprehensive studies on morphine-induced constipation in the small and large intestine by the activation of central and peripheral μ-opioid receptors.

Viewing images of snakes accelerates making judgements of their colour in humans: red snake effect as an instance of 'emotional Stroop facilitation'.

One of the most prevalent current psychobiological notions about human behaviour and emotion suggests that prioritization of threatening stimuli processing induces deleterious effects on task performance. In order to confirm its relevancy, 108 adults and 25 children were required to name the colour of images of snakes and flowers, using the pictorial emotional Stroop paradigm. When reaction time to answer the colour of each stimulus was measured, its value was found to decrease when snake images were presented when compared with when flower images were presented.

Delayed disengagement of attention from snakes in children with autism.

In the visual search task, it is well known that detection of a tilted straight line as the target among vertical lines that act as distractors is easier than vice versa, and that detection of a snake image as the target among flower images is easier than vice versa. In this study, the degree of such search asymmetry was compared between 18 children with autism and 14 typically developing (TD) children. The results revealed that compared to TD children, children with autism were disproportionally slow when asked to detect the flower among the snake images, suggesting the possibility that they experienced difficulty of disengaging their attention from the snake images.

Effects of (+)-pentazocine on the antinociceptive effects of (-)-pentazocine in mice.

Previous studies have shown that sigma-1 receptor chaperone (Sig-1R) ligands can regulate pain-related behaviors, and Sig-1R itself can regulate μ-opioid receptor functions as well as signal transduction. Even though (±)-pentazocine has been used clinically for the treatment of pain through opioid receptors, (+)-pentazocine is known to be a selective Sig-1R agonist. To the best of our knowledge, there is no information available regarding the involvement of Sig-1R agonistic action in the antinociceptive effects of (±)-pentazocine.

Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model.

Background And Purpose: We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain.

Experimental Approach: We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model.

The contribution of Gi/o protein to opioid antinociception in an oxaliplatin-induced neuropathy rat model.

Oxaliplatin is a chemotherapeutic agent that induces chronic refractory neuropathy. To determine whether opioids effectively relieve this chronic neuropathy, we investigated the efficacies of morphine, oxycodone, and fentanyl, and the mechanisms underlying opioid antinociception, in oxaliplatin-induced neuropathy in rats. Rats exhibited significant mechanical allodynia following 2 weeks of chronic oxaliplatin administration.

Establishment of opioid-induced rewarding effects under oxaliplatin- and Paclitaxel-induced neuropathy in rats.

The rewarding effects of μ-receptor agonists can be suppressed under several pain conditions. We recently showed that clinically used μ-receptor agonists possess efficacies for relieving the neuropathic pain induced by chemotherapeutic drug in rats; however, it is possible that the use of μ-receptor agonists may trigger the rewarding effects even under chemotherapeutic drug-induced neuropathic pain. Nevertheless, no information is available regarding whether μ-receptor agonists produce psychological dependence under chemotherapeutic drug-induced neuropathic pain.

Morphine and oxycodone, but not fentanyl, exhibit antinociceptive effects mediated by G-protein inwardly rectifying potassium (GIRK) channels in an oxaliplatin-induced neuropathy rat model.

It has begun to be understood that μ-opioid receptor (MOR) produces ligand-biased agonism, which contributes to differential physiological functions of MOR agonists. We previously demonstrated that in oxaliplatin-induced neuropathy in rats, morphine and oxycodone exhibited antinociceptive effects while antinociception of fentanyl was partial, and such different efficacies might result from the different level of Gi/o protein activation. Based on our background, to reveal further mechanism, we focused on the role of Gi/o protein-related downstream signaling, the G-protein inwardly rectifying K(+)1 (GIRK1) channel.

The color red distorts time perception for men, but not for women.

We investigated the effect of the color red on time perception using a temporal bisection task with human adults. The results showed that the perceived duration of a red screen was longer than was that of a blue screen. However, the results reflected sex differences; men, but not women, overestimated the duration of the red screen.

Involvement of μ- and δ-opioid receptor function in the rewarding effect of (±)-pentazocine.

Most opioid receptor agonists have abuse potential, and the rewarding effects of opioids can be reduced in the presence of pain. While each of the enantiomers of pentazocine has a differential pharmacologic profile, (±)-pentazocine has been used clinically for the treatment of pain. However, little information is available regarding which components of pentazocine are associated with its rewarding effects, and whether the (±)-pentazocine-induced rewarding effects can be suppressed under pain.

Involvement of 5-HT2 receptors in the expression of withdrawal diarrhea in morphine-dependent mice.

The withdrawal syndrome after the cessation of μ-opioid receptor agonists remains an obstacle in the clinical treatment of pain. We recently showed that peripheral opioid receptors play a significant role in the withdrawal signs in morphine-dependent mice. Therefore, the present study was designed to investigate the underlying mechanism of morphine-induced withdrawal symptoms, especially the peripheral oriented body-weight loss that accompanied diarrhea, in mice.

Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc.

Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats.

Previous studies have demonstrated that methylphenidate, MDMA (3,4-methylenedioxymethamphetamine), and other psychostimulants exert stimulant-like subjective effects in humans. Furthermore, MDMA and methylphenidate substitute for the discriminative stimulus effects of psychostimulants, such as amphetamine and cocaine, in animals, which suggests that MDMA and methylphenidate may produce similar discriminative stimulus effects in rats. However, there is no evidence regarding the similarities between the discriminative stimulus effects of MDMA and methylphenidate.

Preliminary evidence that different mechanisms underlie the anger superiority effect in children with and without Autism Spectrum Disorders.

Previous studies have demonstrated that angry faces capture humans' attention more rapidly than emotionally positive faces. This phenomenon is referred to as the anger superiority effect (ASE). Despite atypical emotional processing, adults and children with Autism Spectrum Disorders (ASD) have been reported to show ASE as well as typically developed (TD) individuals.

Japanese monkeys (Macaca fuscata) spontaneously associate alarm calls with snakes appearing in the left visual field.

Many socially living animals are sensitive to a potential predator as part of their antipredator strategy. Alarm calls function to deter predators and to help other group members detect danger. The left visual field is involved in detection of potential threats or predators in many vertebrates, but it is unclear how alarm calls influence visual detection of a potential predator.

G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites.

Background And Purpose: Oxycodone and morphine are μ-opioid receptor agonists prescribed to control moderate-to-severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein-gated inwardly rectifying potassium (K(IR)3 also known as GIRK) channels in their antinociceptive effects.

Comparison of the behavioral effects of bupropion and psychostimulants.

Psychostimulant abuse has been a serious social problem worldwide for a long time. Bupropion, which is used as an antidepressant and to aid smoking cessation in the US, is considered to have psychostimulant-like activity. Although activation of the dopaminergic system induces several behavioral effects and bupropion can activate the dopaminergic system, the abuse potential and other behavioral effects of bupropion have not been fully investigated.

Acamprosate suppresses ethanol-induced place preference in mice with ethanol physical dependence.

The present study investigated the effect of acamprosate on ethanol (EtOH)-induced place preference in mice with EtOH physical dependence. The expression of EtOH (2 g/kg, intraperitoneally)-induced place preference in mice without EtOH treatment before the experiment was dose-dependently suppressed by acamprosate. The levels of protein kinase A (PKA) and phospho-cAMP response element binding protein (p-CREB) in the limbic forebrain after EtOH-conditioning in naïve mice was unchanged.

Mechanisms that underlie μ-opioid receptor agonist-induced constipation: differential involvement of μ-opioid receptor sites and responsible regions.

Reducing the side effects of pain treatment is one of the most important strategies for improving the quality of life of cancer patients. However, little is known about the mechanisms that underlie these side effects, especially constipation induced by opioid receptor agonists; i.e.