Antipsychotics possessing antidepressive efficacy increase Golf protein in rat striatum.

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 Golf protein, a stimulant alpha-subunit of G protein coupled with the dopamine D1 receptor, might a play the key role in the antidepressive effect of antidepressants.

Unique pharmacological profile of aripiprazole as the phasic component buster.

Rationale: Aripiprazole is a recently introduced antipsychotic with a unique pharmacological profile, a dopamine partial agonist. Dopaminergic neural transmission has two different components, tonic and phasic, which have different physiological functions, but the effects of aripiprazole on tonic and phasic components are not reported.

Objective: Studies on antipsychotics including aripiprazole and tonic/phasic dopamine transmission are summarized.

G(olf) protein levels in rat striatum are increased by chronic antidepressant administration and decreased by olfactory bulbectomy.

There are many studies of the mechanisms of antidepressants; however, most of these studies were conducted on the hippocampus or frontal cortex. In the present study, we hypothesized that the nucleus accumbens and caudate/putamen might be major targets for antidepressant effects. Thus, we focused on G(olf) protein, a stimulant alpha-subunit of G protein that is coupled with the dopamine D1 receptor and specifically expressed in the striatum (nucleus accumbens, caudate/putamen and olfactory tubercle) in the rat brain.

The glutamate release inhibitor riluzole attenuates the formation of conditioned place aversion induced by naloxone in rats undergoing a single morphine exposure.

Acute morphine exposure has been hypothesized to produce long-lasting central changes that contribute to the withdrawal aversion. We have most recently demonstrated that those changes may involve the glutamatergic system, including multiple classes of receptors. The present study was undertaken to further determine the involvement of the glutamatergic system by examining the effect of riluzole, a glutamate release inhibitor, on the motivational component of withdrawal from acute morphine dependence.

Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies.

Lithium, a widely used drug for treating affective disorders, is known to inhibit glycogen synthase kinase-3 (GSK-3), which is one of the major tau kinases. Thus, lithium could have therapeutic benefit in neurodegenerative tauopathies by reducing tau hyperphosphorylation. We tested this hypothesis and showed that long-term administration of lithium at relatively low therapeutic concentrations to transgenic mice that recapitulate Alzheimer's disease (AD)-like tau pathologies reduces tau lesions, primarily by promoting their ubiquitination rather than by inhibiting tau phosphorylation.

The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder.

Several genetic studies have revealed that bipolar disorders are linked with the chromosomal locus of 15q11-q13, where the gamma-aminobutyric acid (GABA) receptor alpha5 subunit gene (GABRA5) locates. GABA is one of the major neurotransmitters that may be involved in the pathogenesis of bipolar disorder. Five polymorphisms in the GABRA5 gene, -754C>T in the promoter region, IVS1-21G>A, IVS2-26T>A, (*)302C>T in 3'-UTR of exon 5, and a CA repeat polymorphism in the 3' flanking region were examined in a Japanese population.

Contrasting Fos expression induced by acute reboxetine and fluoxetine in the rat forebrain: neuroanatomical substrates for the antidepressant effect.

Rationale: Antidepressants preferentially facilitating serotonin seem to be particularly effective for treating the anxiety and aggressive component of the depressive syndrome, whereas those with a noradrenergic profile seem to be more effective in reducing psychomotor retardation, although their overall antidepressant effects are about the same. However, the mechanism of this difference remains unknown.

Objectives: To investigate the neural substrate for the different therapeutic efficacies of fluoxetine and reboxetine, we examined the regional Fos immunoreactivity (Fos-ir) induced by the two agents.

Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.

Acute administration of typical and atypical antipsychotics has been reported to induce regionally distinct patterns of c-Fos expression in the rat forebrain. Furthermore, atypical index, the difference in the extent of increased Fos-like immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into typical or atypical antipsychotics. The present study was conducted to investigate the atypical properties of 24 antipsychotics that are used in Japan and blonanserin, a novel 5-HT2A and D2 receptor antagonist.

Withdrawal-induced c-Fos expression in the rat centromedial amygdala 24 h following a single morphine exposure.

Rationale: An opiate antagonist was found to induce motivational withdrawal signs 24 h or even up to 48 h after a single dose of morphine in rats.

Objective: The present study was undertaken to determine whether such a withdrawal state would modify the neuronal activity in the brain.

Methods: A conditioned place aversion was established following a one-trial paradigm in rats undergoing a single exposure to morphine (10 mg/kg) 24 h prior to naloxone administration (0.

No association between the dihydropyrimidinase-related protein 2 (DRP-2) gene and bipolar disorder in humans.

Several susceptibility loci for both of schizophrenia and bipolar disorder (BPD) have been found to overlap on several chromosomes including 8p21. Expression of dihydropyrimidinase-related protein 2 (DRP-2), which gene is located on 8p21, was found to be reduced in the brains of individuals with schizophrenia and BPD. Recently, we demonstrated a significant association between the DRP-2 gene and schizophrenia.

Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder.

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.