Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology最新文献

Glial cells receive neurotransmitters, respond to them, and then release so-called gliotransmitters such as ATP, glutamate or D-serine. Astrocytes in particular have received much attention because synaptic structures are surrounded by astrocytic fine processes, by which astrocytes communicate with neurons via gliotransmitters. Here, we introduce recent progress concerning glia-neuron interaction, especially focusing on the major gliotransmitter ATP and astrocytes in parallel with the latest progress in glia-imaging techniques.

We sometimes make decisions relying not necessarily on deliberative thoughts but on intuitive and emotional processes in uncertain situations. The somatic marker hypothesis proposed by Damasio argued that interoception, which means bodily responses such as sympathetic activity, can be represented in the insula and anterior cingulate cortex and can play critical roles in decision-making. Though this hypothesis has been criticized in its theoretical and empirical aspects, recent studies are expanding the hypothesis to elucidate multiple bodily responses including autonomic, endocrine, and immune activities that affect decision-making. In addition, cumulative findings suggest that the anterior insula where the inner model of interoception is represented can act as an interface between the brain and body in decision-making. This article aims to survey recent findings on the brain-body interplays underlying decision-making, and to propose hypotheses on the significance of the body in decision-making.

Pavlovian fear conditioning is a model of fear learning and memory. The mechanisms regulating fear conditioning and memory have been investigated in humans and rodents. In this paradigm, animals learn and memorize an association between a conditioned stimulus (CS), such as context, and an unconditioned stimulus (US), such as an electrical footshock that induces fear. Fear memory generated though fear conditioning is stabilized via a memory consolidation process. Moreover, recent studies have shown the existence of memory processes that control fear memory following the retrieval of consolidated memory. Indeed, when fear memory is retrieved by re-exposure to the CS, the retrieved memory is re-stabilized via the reconsolidation process. On the other hand, the retrieval of fear memory by prolonged re-exposure to the CS also leads to fear memory extinction, new inhibitory learning against the fear memory, in which animals learn that they do not need to respond to the CS. Importantly, the reinforcement of fear memory after retrieval (i.e., re-experience such as flashbacks or nightmares) has been thought to be associated with the development of emotional disorders such as post-traumatic stress disorder (PTSD). In this review, I summarize recent progress in studies on the mechanism of fear conditioning and memory consolidation, reconsolidation and extinction, and furthermore, introduce our recent establishment of a mouse PTSD model that shows enhancement of fear memory after retrieval.

This review discusses the relationship between therapeutic plasma concentrations of antiparkinson dopamine agonists (rotigotine, pergolide, cabergoline, apomorphine, bromocriptine, ropinirole, pramipexole, and talipexole) and their in vitro pharmacology at dopamine D1, D2 and D3 receptors. A significant correlation was found between therapeutic plasma concentrations of these dopamine agonists and their agonist potencies (EC50) at D2 receptors, although no such correlation existed at D1 or D3 receptors, suggesting that D2 receptors could be the primary and common target for the antiparkinson action of all dopamine agonists. However, D1 receptor stimulation is also important for maintaining swallowing reflex, bladder function and cognition. In particular, continuous D1 and D2 receptor stimulation may be reduced to low levels among Parkinson's disease patients. Our findings revealed therapeutic plasma concentrations of rotigotine were similar to its agonist potencies at both D1 and D2 receptors. Thus, rotigotine may be beneficial for the treatment of Parkinson's disease patients in that this dopamine agonist has the potential of continuous stimulation of both D1 and D2 receptors in the clinical setting.

Stress is a risk factor for psychiatric disorders. Studies using rodent stress models have shown critical roles for inflammation-related molecules in stress-induced behavioral changes. Under chronic mild stress, IL-1beta through IL-1 receptor type 1 (IL-1RI) in the brain activates the hypothalamic-pituitary-adrenal axis, thereby stimulating glucocorticoid release, which in turn decreases motivation to obtain reward. IL-1beta can also suppress proliferation of neural progenitor cells directly through IL-1RI and/or indirectly through glucocorticoid. In repeated social defeat stress, endothelial IL-1RI is involved in stress-induced upregulation of inflammation-related molecules and elevated anxiety. Prostaglandin (PG) E2 and its receptor EP1 mediate elevated anxiety and social avoidance induced by repeated social defeat through attenuating a stress-coping action of the meso-prefrontal dopaminergic pathway. IL-1beta and PGE2 are thought to be released from microglia activated by repeated stress. Whereas the mechanism for stress-induced microglial activation remains elusive, it has been reported that repeated stress induces migration of peripheral macrophages into the brain in a manner dependent on IL-1RI and multiple chemokines, which are also critical for stress-induced elevated anxiety. These findings reveal multiple actions of inflammation-related molecules in the brain and the crosstalk between neurons and microglia as well as that between the brain and the periphery in rodent stress models.

Rearing rodents in social isolation from post-weaning causes abnormal behaviors in adulthood, such as hyper-locomotion, aggression, cognitive impairments, and depression- and anxiety-like behaviors. This social isolation is widely used as a model to study the effects of adverse early-life experiences on behavior and the neural mechanisms associated with neuropsychological development. Previous studies have shown abnormalities of dendritic spine density, synaptic protein levels and amine metabolism in the prefrontal cortex and hippocampus of isolation-reared animals, but the neurochemical basis for induction of abnormal behaviors is not known. We have established a novel methodology for assessing social interaction, focusing on the psychological stressor responsible for induction of abnormal behaviors as a transient environmental factor. This review summarizes the effect of a social encounter with an unfamiliar conspecific on behavior and neurochemistry in isolation-reared mice. The current analysis using the encounter response will provide new strategies to clarify the pathophysiology of psychiatric disorders including schizophrenia, depression and drug dependence.

The Japanese Society of Neuropsychopharmacology (NP) has established a Translational Medical Science Committee (TMSC), which is introduced in this article. In this century, the Japanese Government has made great effort to establish highly organized supporting systems for translational research (TR); however, clinical developments for psychotropic drugs in Japan are facing stagnation. TMSC will provide advisory activities from an academic point of view in this field, which will be result in the improvement of people's health.

Hippocampal cholinergic neruostimulating peptide (HCNP) induces acethylcholine synthesis in the adult hippocampus of mice via increasing the amount of cholineacethyl transferase. The precursor protein of HCNP (HCNP-pp), composed of 186 amino acids, is a multifunctional protein, such as c-Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein. In the adult hippocampus, HCNP-pp co-localizes in presynapse terminals with non-phosphorylated collapsin response mediator protein (CRMP)-2, and might play a crucial role in hippocampal neuronal activity. The quantitative alteration of HCNP-pp might be related to the phosphorylation of CRMP-2. The expression of HCNP-pp mRNA is decreased in hippocampal pyramidal neurons of CA1 from the early stage in Alzheimer's disease. The HCNP-related antigens are also deposited in the Hirano body, one locus of Alzheimer pathology. CRMP-2 is one of microtubule-associated proteins such as tau protein, and its phosphorylated form increased in the hippocampus of Alzheimer brains. HCNP and HCNP-pp might be candidates for the key molecules as a therapeutic target in Alzheimer's disease.

Schizophrenia and bipolar disorder are severe neuropsychiatric disorders, affecting about 1% of the population. Identifying endophenotypes in the brains of neuropsychiatric patients is now considered the way to understand the underlying mechanisms and to improve therapeutic outcomes. However, the endophenotypes and brain mechanisms of the disorders remain unknown. We have previously reported that alpha-CaMKII heterozygous knockout mice show abnormal behaviors related to neuropsychiatric disorders. In these mutant mice, almost all neurons in the hippocampal dentate gyrus stay at a pseudo-immature state, which we refer to as "immature dentate gyrus (iDG)." So far, the iDG phenotype and similar behavioral abnormalities have been found in Schnurri-2 knockout, SNAP-25 mutant, and forebrain-specific calcineurin knockout mice. In addition, we found that both chronic fluoxetine treatment and pilocarpine-induced seizures can reverse the maturation state of the mature neurons, resulting in the iDG phenotype in wild-type mice. Such an iDG-like phenomenon was observed in the post-mortem brains from patients with schizophrenia/bipolar disorder. Recent studies suggest that cortex and amygdala of schizophrenia patients are also at a pseudo-immature state. Based on the findings, we proposed that immaturity of certain types of cells in the brain is a potential endophenotype of neuropsychiatric disorders.