Search

The present study was performed to investigate the effects of kavain on the sleep-wake cycle in comparison with that of rilmazafone and diphenhydramine using sleep-disturbed rats. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were implanted into Wistar rats. Total awake time, non-rapid eye movement (non-REM) sleep and rapid eye movement (REM) sleep were measured for 6 h. Kavain and rilmazafone showed a significant shortening in sleep latency, decreased awake time, and increased non-REM sleep time. On the other hand, significant shortening of the sleep latency was observed following the administration of diphenhydramine, while no effects were observed on the awake and non-REM sleep time. Moreover, kavain showed a significant increase in delta activity during non-REM sleep in sleep-disturbed rats, whereas a significant decrease in delta power during non-REM sleep was observed with rilmazafone. These results clearly indicate that kavain is a compound with not only hypnotic effects, but also sleep quality–enhancement effects. Keywords:: kavain, hypnotic effect, kava-kava, sleep

The effect of [pGlu4,Cyt6,Arg8]-vasopressin fragment 4-9 (AVP4-9) on group I metabotropic glutamate (mGlu1) receptor antagonist–induced memory deficits was studied using 8-arm radial maze performance with 4 arms baited. In addition, the participation of the cholinergic system in the ameliorating effect of AVP4-9 on mGlu1 receptor antagonist–induced memory deficits was also investigated. Intrahippocampal injection of (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA), an mGlu1-receptor antagonist, significantly increased total error, reference memory error, and working memory error at a dose of 20 nmol/side. AVP4-9 (0.1 and 1.0 μg/kg, s.c.) showed a significant ameliorative effect on AIDA-induced memory deficits. Improvement of AIDA-induced memory deficit in response to AVP4-9 treatment was significantly antagonized by scopolamine (5 nmol/side) but not by mecamylamine (200 nmol/side) at a dose that caused no effect on performance when injected separately. These findings indicate that the ameliorating effect of AVP4-9 on AIDA-induced memory deficit may be closely associated with the muscarinic receptor. Keywords:: [pGlu4,Cyt6,Arg8]-vasopressin fragment 4-9, group I metabotropic glutamate receptor (mGlu1), 8-arm radial maze, reference memory error, working memory error

Triazolam caused no significant increase in the total error at 0.05 and 0.1 mg/kg. However, at 0.2 mg/kg, it caused a significant increase in total error. Almost the same findings were observed with brotizolam and rilmazafone. That is, at 0.2 and 0.5 mg/kg of brotizolam, 0.5 and 1.0 mg/kg of rilmazafone caused no significant increase in the total error. However, brotizolam at 1.0 mg/kg and rilmazafone at 2.0 mg/kg caused a significant increase in total error. Triazolam (0.05 mg/kg) and ethanol (1.0 g/kg) showed no significant effect on the numbers of errors when used alone separately, but the simultaneous use of triazolam and ethanol caused a significant increase in total error. Almost the same findings were observed with the coadministration of brotizolam (0.2 mg/kg) or rilmazafone (0.5 mg/kg) with ethanol. These results clearly indicate that all the short-acting benzodiazepines used in the study showed potentiation by ethanol in spatial memory deficits in mice. Keywords:: triazolam, brotizolam, rilmazafone, ethanol, radial maze

The role of central histamine in amygdaloid kindled seizures in rats was studied. Histamine content in the amygdala was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H1-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine- or histidine-induced inhibition of amygdaloid kindled seizures. Both i.c.v. and i.p. injections of H3-antagonists (thioperamide, AQ0145 and clobenpropit) resulted in a dose-related inhibition of amygdaloid kindled seizures. The effects of thioperamide and AQ0145 were inhibited by an H3-agonist (R)-alpha-methylhistamine and H1-antagonists. On the other hand, H2-antagonists showed no antagonistic effect. GABAmimetic drugs, diazepam, sodium valproate and muscimol potentiated the effect of clobenpropit. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H1-receptors. In addition, an inhibition of amygdaloid kindled seizures induced by histamine is closely related with the action of GABA.

The behavioral and electroencephalographic effects of Clozapine were investigated in mice, rats and rabbits, and compared with chlorpromazine and perphenazine. Clozapine showed in general the pharmacologic properties characteristic to neuroleptics, such as decrease in exploratory behavior, suppression of conditiond avoidance response, taming effects, anti-methamphetamine and so on. These effects were less potent and shoter in duration than those of chlorpromazine and perphenazine. Clozapine, however, lacked cataleptogenic propeties and depressed the EEG arousal responses induced not only by auditory but also by mesencephalic reticular stimulation, differently from chlorpromazine and perphenazine.