Effects of MK-801 on the expression of serine racemase and d-amino acid oxidase mRNAs and on the D-serine levels in rat brain.

We have investigated the acute effects of the increasing doses of non-competitive N-methyl-d-aspartate receptor antagonist MK-801 (0.2-1.6 mg/kg) on the expression of serine racemase and d-amino acid oxidase (DAO) mRNAs in several brain areas of rats. We have also evaluated the effects of the chronic administration of MK-801 (0.4 mg/kg) on the gene expression of serine racemase and DAO and on the d-serine concentrations. A dose-dependent augmentation of the expression of serine racemase mRNA was seen in most brain areas at both 1 and 4 h after the administration. In contrast, a drastic decline in the expression of DAO mRNA was observed in most brain areas 1 h after the MK-801 administration, whereas a dose-dependent elevation in the expression of DAO mRNA was observed in most brain areas 4 h after the administration. The chronic MK-801 administration produced a significant increase in the expression of serine racemase mRNA in almost all brain areas, whereas no significant changes were found in the level of DAO mRNA in most brain areas. In addition, the chronic administration caused a slight but significant elevation in the concentrations of d-serine in the cortex and striatum. These present findings indicate that increasing the serine racemase mRNA and no changes in the DAO mRNA after the chronic administration could contribute to the elevation of the d-serine level in the forebrain, and that serine racemase and DAO could play an important role in the regulation of N-methyl-d-aspartate receptors via the d-serine metabolism.

Acute treatment with morphine augments the expression of serine racemase and D-amino acid oxidase mRNAs in rat brain.

To obtain further insight into the interactions between the N-methyl-D-aspartate receptor and opioid receptor systems, we have investigated the effects of the acute treatment of morphine on the expression of serine racemase and D-amino acid oxidase mRNAs in several brain areas of rats. The morphine administration produced a dose-dependent and transient elevation in the levels of serine racemase and D-amino acid oxidase mRNAs in all the brain areas. The present results are the first to suggest an interaction between the expression of the mRNAs for the D-serine-related enzymes and the opioid receptor activation.

Early crisis intervention to patients with acute stress disorder in general hospital.

This report presents 2 patients who were diagnosed to have acute stress disorder (ASD), received early psychiatric intervention (crisis intervention as a short-term psychotherapy), and subsequently had good outcome. Encounter with an event that causes psychological trauma may induce post-traumatic stress disorder (PTSD). However, the 2 patients described here have shown no particular mental symptoms for more than 2 years after the event and are leading normal lives. Psychological debriefing as a group used to be regarded as effective for the prevention of PTSD, but early identification of the stress-related disorder and intensive treatment of individual patients is recently considered to be more necessary. Both of the 2 patients presented here showed good outcome, and early crisis intervention in individual patients is suggested to be effective for the treatment of stress-related disorders and prevention of PTSD.

Chronic administration of methamphetamine increases the mRNA expression of diazepam binding inhibitor in rat brain.

Anxiety is one of the common features of withdrawal syndrome caused by abuse-inducing drugs such as methamphetamine (MAP). The neural pathways associated with anxiety are established within the network sustained by diencephalon, cerebral cortex, cerebellum and hippocampus. Diazepam binding inhibitor (DBI), a peptide consisting of 87 amino acids, serves as an inverse agonist for the type A receptor of the gamma-aminobutyric acid (GABAA receptor) with endogenous anxiogenic potential. We examined the effect of chronic administration of MAP on the mRNA expression of DBI and DBI-related proteins, such as alpha 2 subunit of GABAA receptor (GABA-α2), peripheral-type benzodiazepine receptor (PBR), and pituitary adenylate cyclase-activating polypeptide (PACAP) in seven regions (diencephalon, cerebral cortex, cerebellum, striatum, hippocampus, midbrain, and pons-medulla) of the rat brain. The mRNA expression of DBI increased significantly in all areas of the brain, especially diencephalon, after chronic administration of MAP. The mRNA expression of PBR, GABA-α2 and PACAP increased significantly in all areas of the brain, especially cerebral cortex, after chronic administration of MAP. These results suggest that anxiety is associated with the mRNA expression of DBI as well as DBI-related genes.

The selective action of D2 dopamine receptor antisense oligodeoxynucleotide on the expression of the dopamine receptor subtype mRNA in rat striatum.

We have evaluated the effect of the D2 dopamine receptor antisense oligodeoxynucleotide (D2 AS ODN) on the gene expression of all five dopamine receptor subtypes including D1, D2, D3, D4 and D5 dopamine receptor in the rat striatum. The levels of D2 dopamine receptor mRNA are significantly decreased at 6, 12, 24 h after the last injection of three time injections of D2 AS ODN, although D1, D3, D4 and D5 subtype mRNA levels did not significantly reduced at any time. The present study is the first to demonstrate the selective effect of D2 AS ODN on D2 dopamine receptor mRNA among all five dopamine receptor subtypes and the effectiveness of D2 AS ODN without 6-hydroxydopamine.

Characteristics of suicide attempters with depressive disorders.

Attempted suicide is known to be an important risk factor of committed suicide. Past studies of the relationship of attempted suicide with mental disorders have shown that it is most closely related to depression. The objective of the present study was to clarify characteristics of depression and measures to prevent committed suicide by comparing depression with other mental disorders. The patients with depression were significantly more often aged, males, married, and used methods other than poisoning by solids or liquids compared with patients with other mental disorders. Particularly, the major risk factors of attempted suicide (i.e. a younger age and the female gender), did not apply to our depressed patients. These results suggest that approaches such as intensive psychiatric treatment may lead to the prevention of committed suicide in older male patients with depression who have attempted suicide.