Lithium has been used widely for the treatment of manic states. Since amphetamines produce effects in humans similar to the symptoms of idiopathic mania, amphetamine administration to animals has ...been proposed as a model of this condition. To investigate the neurobiologic substrates of the antimanic effects of chronic lithium administration, we investigated its effects on methamphetamine-induced regional Fos protein expression in the rat brain. Chronic lithium administration (14 days; serum lithium concentration, 0.41+/-0.02 mEq/l) significantly reduced the number of neuronal nuclei showing immunoreactivity induced by methamphetamine (2mg/kg) in the prefrontal cortex, caudate/putamen, nucleus accumbens, and central nucleus of the amygdala. These results indicate the structural basis in CNS which is responsible for the antimanic effect of lithium.
Brain-derived neurotrophic factor (BDNF) belongs to a family of neurotrophic factors and has been demonstrated to promote the survival, differentiation, and maintenance of a broad variety of central ...nervous system neurons. Several reports have suggested that the BDNF gene is a plausible functional candidate gene underlying the predisposition for developing bipolar disorder (BPD). In the present study, we investigated the possible role of the BDNF gene in the etiology of BPD using a matched case-control association design in a Japanese population. There was no evidence for an allelic or genotypic association of two polymorphisms (−1360C>T and 196G>A) of the BDNF gene with BPD. Furthermore, no significant association was observed between these polymorphisms and either of two diagnostic subtypes (bipolars I and II disorder). The results suggest that the BDNF gene is unlikely to confer susceptibility to BPD.
The present study examined effects of selective antagonists of D-1 and D-2 dopamine receptors on the development of behavioral sensitization produced by repeated methamphetamine (MAP) administration. ...Male Sprague-Dawley rats were divided into four groups. Each group received a daily injection of saline (control group), 4 mg/kg MAP (MAP group), 1 mg/kg YM-09151-2 plus 4 mg/kg MAP (YM + MAP group) or 0.5 mg/kg SCH 23390 plus 4 mg/kg MAP (SCH + MAP group) for 14 days. During daily injection for 14 days, the MAP group exhibited a progressive augmentation in locomotor and stereotyped behavior, whereas the progression of such behaviors in the YM + MAP and SCH + MAP group was completely prevented. After an abstinence period of 7 days, all groups received a challenge of 2 mg/kg MAP. The MAP challenge reproduced hyperlocomotion and intense stereotyped behavior only in the MAP group. However, neither the YM + MAP group nor the SCH + MAP group showed stereotypy. The manner in which both groups showed only hyperlocomotion was similar to that observed in the control group. These results indicate that both selective D-1 antagonists and selective D-2 antagonists not only reverse MAP-induced motor effects at each injection but also prevent the development of behavioral sensitization induced by repeated MAP administration.
The effect of MK-801 on striatal dopamine (DA) release was investigated by using an in vivo microdialysis technique in the freely moving rat. Systemic injection of MK-801 (0.25, 0.5, 1, 2 mg/kg, ...i.p.) reduced the extracellular level of DA significantly and produced no change in the level of 3,4-dihydroxyphenylacetic acid. The behavioral observation, recorded simultaneously, revealed that MK-801, with smaller doses, produced ipsilateral circling toward the side with the dialysis probe. At larger doses, MK-801 predominantly evoked ataxia. These findings indicate that the behavioral effect of MK-801 may not be mediated via the release of DA.
This study examines the effects of the design variables of a continuous crystallization process on the production rate of the large crystals and ease of control. The ease of control for a given ...design of a crystallizer is evaluated using indices which indicate the relative strength of the control action and physical feedback effects. It is shown that an increase in the volume of the external heater or the cross sectional area of the annular settling zone enlarges the area of operating condition, where the crystallizer can be easily controlled. However, an increase in either one of these design variables decreases the feasible area or the production rate of large crystals. It is shown that by properly adjusting both the design variables it is possible to increase the production rate of large crystals without narrowing the area of the feasible operating conditions.
The effect of acute and chronic administration of methamphetamine (METH) on the levels of calmodulin (CaM) and its mRNAs has been investigated in rat brain using antisense oligonucleotides to three ...distinct rat CaM genes (CaM I, CaM II, CaM III). CaM I mRNA was reduced in the striatum and nucleus accumbens within 2 h of acute administration of 4 mg/kg METH, but returned to the control level by 6 h. The CaM content in both the cytosolic and membrane fractions of the striatum was reduced 0.5, 2, and 6 h after acute administration of METH. In the chronic experiments, rats were treated with either 4 mg/kg METH or saline once daily for 14 days. This was followed by a withdrawal period of 28 days, and thereafter, the animals were challenged with either METH (4 mg/kg, i.p.) or saline. All the animals were decapitated 6 h after this injection. There were four treatment groups: METH-METH (MM); METH-saline (MS); saline-METH (SM); and saline-saline (SS). There was a significant decrease in the mRNA for CaM I and CaM II in the striatum, and CaM II and CaM III in the nucleus accumbens in the MS group and the MS and MM groups, respectively, when compared to the SS group. The CaM content in the striatal membrane fraction decreased in both the SM and MS groups but not in the MM group. In contrast, the CaM content in the membrane fraction of the mesolimbic area showed a significant increase in the MM group. The CaM content in the cytosolic fraction of these brain areas decreased in both the SM and MM groups. The total CaM decreased significantly in the SM and MM groups of the striatum, but increased significantly in the MM group of the mesolimbic area. The mRNA for CaM I and CaM III decreased significantly in the MM group, and in the SM and MM groups, in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA), respectively. The CaM content in both the cytosolic and membrane fractions and total CaM content of the SN/VTA decreased significantly in the SM, MS and MM group as compared with the SS group. In the medial prefrontal cortex and hippocampus the significant increase of CaM content in the membrane fraction of the MM group was also found, but neither the CaM content in the cytosol fraction nor total CaM content changed. These results suggest that chronic METH administration leads to a translocation of CaM from the cytosolic to membrane fractions; these may underlie METH-induced behavioral sensitization.
Introduction
Recently, second-generation antipsychotics (SGAs) have been widely used in the treatment of mood disorders. However, the mechanisms of the antidepressant effect of SGAs remain unclear. ...We proposed that G
olf
protein, a stimulant α-subunit of G protein coupled with the dopamine D1 receptor, might a play the key role in the antidepressive effect of antidepressants. To clarify the relationship between G
olf
protein and the antidepressive effects of antipsychotics, we examined the effects of chronic treatment with several antipsychotics on the level of G
olf
protein in the rat striatum.
Materials and methods
Male Wistar rats were treated with one of several antipsychotics for 2 weeks: olanzapine (2, 5, or 10 mg/kg), sulpiride (5, 10, or 50 mg/kg), amisulpride (3, 10, or 20 mg/kg), risperidone (0.2 or 2 mg/kg), haloperidol (0.3 or 3 mg/kg), or clozapine (2 or 10 mg/kg).
Results and discussion
Olanzapine (5 mg/kg), sulpiride (5, or 10 mg/kg), and amisulpride (10 mg/kg) treatments significantly increased the level of G
olf
protein, but there was no increase with administration of higher doses of these three antipsychotics. Risperidone, haloperidol, and clozapine treatment did not change the level of G
olf
protein at any dose. In this study, all antipsychotics that have antidepressive effects increased G
olf
protein. This suggests that an increase in G
olf
may play an important role in the antidepressive effect of antipsychotics.
Conclusion
We postulate that the increase in G
olf
protein levels result in an increase the proportion of D1 receptors in the high-affinity state and that augmentation of the dopaminergic system exerts the antidepressant effect.
The optimal operation of a continuous crystallizer is studied by taking a real industrial scale crystallizer as an example. The objective function to be maximized is the production rate of the ...crystals which are larger than a certain size. Since continuous crystallizers exhibit sustained oscillation, it is important to find the optimal operation under oscillatory condition. In this study, the optimal operating condition is derived for two types of operation: one is the case where the manipulated variables are kept constant (constant input operation), and the other is the case where the values of manipulated variables are changed periodically (time varying input operation). The optimization result of time varying input operation indicates that the production rate of large crystals can be increased if the number of fine crystals in the vessel is reduced by withdrawing along with the product. Furthermore, this study examines the optimal operation of the crystallizer in the case where the sustained oscillation is eliminated by a stabilizing controller. The optimization result clearly indicates that the production rate of large crystals can be significantly increased if the operation is optimized under the condition where crystal size distribution (CSD) is stabilized.
