Biomedical subjects

Takahiro Seki

Publications and source records attributed to Takahiro Seki.

23 records · Page 2Linked to original sources

PubMed2003

Repeated administration of methamphetamine causes hypersensitivity of D2 receptor in rat ventral tegmental area.

To elucidate whether the methamphetamine (MAP)-induced hypersensitivity to dopamine occurs in the ventral tegmental area (VTA), patch clamp studies were performed using brain slice preparations. MAP or physiological saline was administered to 8-10-day-old rats daily for 5 days. On day 5, patch clamp studies were performed on VTA dopamine neurons which were identified by morphological and electrophysiological characteristics. Dopamine (1-100 microM) and talipexole (a dopamine D2 receptor agonist, 1-100 microM) produced a dose-dependent hyperpolarization in these neurons; treatment with SKF 38393 or PD128907 (Dl and D3 receptor agonists, respectively) had no effect. The extent of hyperpolarization was significantly greater in the MAP group compared to the saline controls, suggesting that repeated MAP administration causes a hypersensitivity to dopamine that is D2 receptor-dependent. This hypersensitivity reduces the excitability of VTA dopamine neurons, thus decreasing dopamine release in the nucleus accumbens area. This may compensate for the MAP-induced elevation of dopamine levels and modulate the dopamine-induced signal transduction cascades, leading to reverse tolerance in nucleus accumbens neurons.

Animals↗

PubMed2003

Perospirone, a novel antipsychotic agent, hyperpolarizes rat dorsal raphe neurons via 5-HT1A receptor.

To investigate the effect of cis-N-[4-[4-(1,2-benz-isozole-3-yl)-1-piperazinyl]butyl] cyclohexane-1,2-dicarboximide hydrochloride (perospirone), a novel antipsychotic agent with high affinities for D(2)/5-HT(2) receptors, on the rat dorsal raphe (DR) neurons, an electrophysiological study was performed using the tight-seal whole-cell patch-clamp technique. Applications of perospirone at the concentration between 10(-)(9) and 10(-)(5) M hyperpolarized the membrane potential and inhibited spontaneous action potentials of the DR neurons in a concentration-dependent manner. This effect of perospirone on DR neurons is similar to that of typical 5HT(1A)-receptor agonists, including 8-OH-DPAT or tandospirone. In addition, WAY100635, a 5-HT(1A)-receptor antagonist, inhibited this perospirone-induced hyperpolarization of DR neurons, suggesting that perospirone physiologically acts on DR neurons as a 5HT(1A)-receptor agonist. These results provide new profiles of perospirone as an antipsychotic drug.

Animals↗

PubMed2003

Electrophysiological characterization of nicotine-induced excitation of dopaminergic neurons in the rat substantia nigra.

The electrophysiological characteristics of nicotine-induced excitation of dopaminergic neurons in the rat substantia nigra was investigated using the whole-cell patch clamp technique under the voltage-clamp mode. Nicotine (0.01 - 100 microM) induced inward currents corresponding to nicotine-induced depolarization with an increase in firing in a dose-dependent manner. This current was inhibited by dihydro-beta-erythroidine, a selective antagonist for the alpha4beta2 type neuronal nicotinic receptor. Nicotine directly acts on postsynaptic alpha4beta2 type nicotinic receptors and induces inward currents, resulting in excitation of dopaminergic neurons in the substantia nigra and subsequent enhancement of dopamine release in the corpus striatum.

Animals↗

PubMed2002

Adenoviral gene transfer of aspartoacylase into the tremor rat, a genetic model of epilepsy, as a trial of gene therapy for inherited epileptic disorder.

The tremor rat (tm/tm) is a genetic model of epilepsy that exhibits absence-like seizures characterized by 5-7 Hz spike-wave-like complexes in cortical and hippocampal electroencephalograms (EEGs). A deletion of the aspartoacylase (ASPA) gene and resultant high levels of N-acetyl-aspartate (NAA) in the brain have been found in tremor rats. We attempted to determine whether gene transfer of ASPA inhibited absence-like seizures in tremor rats using recombinant adenovirus. Recombinant adenovirus (5x10(7) pfu) carrying the rat ASPA gene (AxASPA) or beta-galactosidase gene (AxLacZ), as a control virus, was intracerebroventricularly administered to premature tremor rats aged 7 weeks. Cortical and hippocampal EEG were recorded with chronically implanted electrodes before and after viral administration. The absence-like seizures were increased in AxLacZ-administered control rats with age. However, the increase was significantly inhibited in AxASPA-administered rats at 1 week after treatment. These results suggest that gene transfer of ASPA is effective in inhibiting the generation of absence-like seizures, probably by reducing the NAA level.

Adenoviridae↗

PubMed2002

Abrupt interfacial transitions of hydrophobic polysilanes as probed via liquid crystal-assisted stepwise deposition.

The Langmuir-Blodgett deposition was applied for the first time for fully hydrophobic polysilanes, poly(di-n-hexylsilane) (PDHS) and poly(methyl-n-octylsilane) (PMOS). The monolayer formation of such hydrophobic polysilanes was achieved by cospreading with a liquid crystal molecule, 4'-pentyl-4-cyanobiphenyl (5CB). The UV-visible absorption spectra showed that the backbone conformations of the polysilanes are completely different from that in the bulk. The layer-by-layer deposition allowed for the nanometer level evaluation of the thickness profile on the conformational changes. It is found that the conformational change of these hydrophobic polysilanes abruptly occurs at a monolayer level thickness boundary.

Journal Article↗