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Kihito (KIT; Gui Pi Tang) is a traditional herbal medicine that is used for treatment of neuropsychiatric disorders such as depression, anxiety, neurosis and insomnia in China and Japan. Recently, it has also been shown that KIT improves cognitive dysfunction in patients with Alzheimer's disease. In this study, to investigate the mechanisms underlying the effects of KIT on stress-induced brain dysfunctions such as a depressed state and memory impairment, we examined whether KIT prevents behavioral and neurophysiological abnormalities in mice treated chronically with corticosterone (CORT). CORT (40 mg/kg/day, s.c.) and KIT (1000 mg/kg/day, p.o.) were given to 7-week-old male ddY mice for 14 days. Twenty-four hours after the last treatment, depression-like behavior in the forced swim test, spatial memory in the Barnes maze test, cell survival and the number of new-born immature neurons, dendritic spine density and expression levels of mRNA for neurotrophic factors were analyzed. Depression-like behavior and spatial memory impairment were observed in CORT-treated mice without KIT treatment. Hippocampal cell survival, the number of hippocampal new-born immature neurons, hippocampal and accumbal dendritic spine density and mRNA levels for neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) were decreased in CORT-treated mice without KIT treatment. KIT prevented CORT-induced depression-like behavior, spatial memory impairment, and decreases in hippocampal cell survival, the number of hippocampal new-born immature neurons, accumbal dendritic spine density and GDNF mRNA. KIT may ameliorate stress-induced brain dysfunctions via prevention of adverse effects of CORT on cell survival, new-born immature neurons, spine density and neurotrophic factors.

Post-weaning social isolation of laboratory animals is known to induce many behavioural and neurochemical abnormalities, which resemble neuropsychiatric disorders such as depression and anxiety. Therefore, they can help provide a suitable animal model to investigate the pathophysiology of neuropsychiatric symptoms and explore potential drugs for the treatment of neuropsychiatric diseases. Our recent studies have demonstrated that post-weaning social isolation of mice for no less than one week causes behaviour changes such as reduced attention, impaired social affiliation behaviour, and impaired conditional fear memories. Our neuropharmacological analyses have revealed that these behavioural features are modulated by different neuronal mechanisms, suggesting that post-weaning social isolation of mice can help provide an animal model with comorbid symptoms of patients with developmental disorders, including attention-deficit hyperactivity disorder, autism spectrum disorder, and specific learning disability. In this review, we discuss the neuropharmacological features of developmental disorder-like behaviour induced by post-weaning social isolation in mice to offer new insights into the pathophysiology of developmental disorders and possible therapeutic strategies.

The aging-dependent activation of glycogen synthase kinase-3β (GSK-3β) has been suggested to be important in the onset of dementia. To discover novel therapeutic Kampo medicines for dementia, we examined the effects of orengedokuto (OGT; 黃連解毒湯 huáng lián jiědú tāng) and san'oshashinto (SST; 三黃瀉心湯 sān huáng xiè xīn tāng) on memory deficits and GSK-3β activity in senescence-accelerated prone mice (SAMP8).

Kamiuntanto (KUT; Jia Wei Wen Dan Tang in Pinyin) is a traditional Japanese Kampo medicine that is used to treat psychological dysfunction. However, the mechanisms of action of KUT are not understood. To investigate the mechanisms underlying the ameliorative properties of KUT, the effects of KUT on abnormal behaviors of isolation-reared mice and on the prefrontal monoaminergic system were examined. KUT (1000 mg/kg) reversed encounter-induced hyperactivity and increased immobility in the forced swim test in isolation-reared mice, as also found for an antidepressant, fluoxetine (30 mg/kg). In vivomicrodialysis showed that KUT (1000 mg/kg) transiently increased the level of extracellular serotonin (5-HT) in the prefrontal cortex. In contrast, an incomplete KUT formula excluding Bambusae Caulis (BC), a component herb of KUT, did not reverse abnormal behaviors of isolation-reared mice or increase prefrontal extracellular 5-HT. Furthermore, the antidepressant-like effect of KUT in the forced swim test was prevented by pretreatment with GR127935, a 5-HT1Bantagonist. These findings suggest that KUT may ameliorate depressive symptoms via 5-HTergic systems, and that BC plays an important role in the antidepressant-like effects of KUT.

Social isolation (SI) mice exhibit behavioral abnormalities such as impairments of sociability- and attention-like behaviors, offering an animal model of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to identify the effects of Sansoninto (SST; 酸棗仁湯 suān zǎo rén tāng) on the psychiatric symptoms related to ADHD using SI mice. Four-week-old mice were socially isolated during the experimental period, and SST administration (800 or 2400 mg/kg, p.o.) was started at 2 weeks after starting SI. SST ameliorated SI-induced impairments of sociability- and attention-like behaviors in a dose-dependent manner, and tended to ameliorate contextual- and auditory-dependent fear memory deficit. Moreover, the expression level of Egr-1 was down-regulated by SI stress, and was restored by a high dose of SST. These findings suggest that SST is useful for improvement of psychiatric disorders such as ADHD.

Chotosan(CTS), a traditional herbal formula called Kampomedicine, was shown to be effective in the treatment of vascular dementia in a clinical study, and exerted protective effects against transient cerebral ischemia-induced cognitive impairment in mice. In the present study, we investigated the neuroprotective effects of CTS using primary cultured rat cortical neurons. CTS (250–1000 μg/mL) inhibited neuronal death induced by 100 μM glutamate. This glutamate-induced neuronal death was blocked by a GluN2B-, but not GluN2A-containing NMDA receptor antagonist. Therefore, the neuroprotective effects of CTS were related to an inhibition of GluN2B-containing NMDA receptor-mediated responses.

We previously demonstrated that chotosan(CTS), a traditional herbal formula called Kampomedicine, improves diabetes-induced cognitive deficits. In the present study, we investigated the antidepressant-like effects of CTS in mice. The administration of CTS (1.0 g/kg, for 3 days) decreased the immobility time in the forced-swim test, and this decrease was prevented by the prior administration of sulpiride (an antagonist of D2/3receptors) and WAY100635 (an antagonist of 5-HT1Areceptors). None of the treatments tested altered the locomotor activity of mice. These results suggest that CTS exerts antidepressant-like effects through changes in the serotonergic and dopaminergic systems.

The nicotinic acetylcholine receptors (nAChRs) are a member of the ligand-gated ion channel family and play a key role in the transfer of information across neurological networks. The X-ray crystal structure of agonist-bound α7acetylcholine binding protein (AChBP) has been recognized as the most appropriate template to model the ligand-binding domain of nAChR for studying the molecular mechanism of the receptor–ligand interactions. Virtual screening of the National Cancer Institute diversity set, a library of 1990 compounds with nonredundant pharmacophore profiles, using AutoDock against AChBPs revealed 51 potential candidates. In vitro radioligand competition assays using [3H] epibatidine against the AChBPs from the freshwater snails, Lymnaea stagnalis, and from the marine species, Aplysia californicaand the mutant (AcY55W), revealed seven compounds from the list of candidates that had micromolar to nanomolar affinities for the AChBPs. Further investigation on α7nAChR expressing in Xenopusoocytes and on the recombinant receptors with fluorescence resonance energy transfer (FRET)–based calcium sensor expressing in HEK cells showed that seven compounds were antagonists of α7nAChR, only one compound (NSC34352) demonstrated partial agonistic effect at low dose (10 µM), and two compounds (NSC36369 and NSC34352) were selective antagonists on α7nAchR with moderate potency. These hits serve as novel templates/scaffolds for development of more potent and specific in the AChR systems.

Serotonin 2C receptor (5-HT2CR) mRNA receives editing at 5 nucleotide positions (sites A – E) located in the sequence encoding the second intracellular loop of 5-HT2CR. 5-HT2CR mRNA without editing and with editing at sites AB, ABD, ABC, ABCD, and C are translated to 6 isoforms of 5-HT2CR: INI(non-edited), VNI(AB), VNV(ABD), VSI(ABC), VSV(ABCD), and ISI(C), respectively. In this study, we investigated electrophysiologically the ability of these isoforms to couple with the G protein / phospholipase C (PLC) system using Xenopusoocytes injected with edited 5-HT2CR RNAs and muscarinic M1receptor (M1R) RNA. The efficacy with which 5-HT stimulated each isoform was calculated by comparing 5-HT–induced current with 100 μM acetylcholine–induced M1R current. Stimulation with 5-HT of INI(non-edited), VNI(AB), VNV(ABD), VSI(ABC), VSV(ABCD), and ISI(C) expressed in Xenopusoocytes showed concentration-dependent responses with EC50values of 8.6, 17.2, 76,5, 22.0, 91.2, and 20.3 nM, respectively. No significant difference in the ability of 5-HT to induce currents among the oocytes expressing these isoforms was detected, but in the oocytes expressing VSI(ABC) or VSV(ABCD), 5-HT had a significantly reduced ability to induce currents. These results suggest that editing at site C together with sites A and B and/or D markedly reduces 5-HT2CR function by generating isoforms with reduced ability to activate PLC.

We previously demonstrated that the Kampoformula chotosan(CTS) ameliorated spatial cognitive impairment via central cholinergic systems in a chronic cerebral hypoperfusion (P2VO) mouse model. In this study, the object discrimination tasks were used to determine if the ameliorative effects of CTS on P2VO-induced cognitive deficits are a characteristic pharmacological profile of this formula, with the aim of clarifying the mechanisms by which CTS enhances central cholinergic function in P2VO mice. The cholinesterase inhibitor tacrine (THA) and Kampoformula saikokeishito(SKT) were used as controls. P2VO impaired object discrimination performance in the object recognition, location, and context tests. Daily administration of CTS (750 mg/kg, p.o.) and THA (2.5 mg/kg, i.p.) improved the object discrimination deficits, whereas SKT (750 mg/kg, p.o.) did not. In ex vivo assays, tacrine but not CTS or SKT inhibited cortical cholinesterase activity. P2VO reduced the mRNA expression of m3and m5muscarinic receptors and choline acetyltransferase but not that of other muscarinic receptor subtypes in the cerebral cortex. Daily administration of CTS and THA but not SKT reversed these expression changes. These results suggest that CTS and THA improve P2VO-induced cognitive impairment by normalizing the deficit of central cholinergic systems and that the beneficial effect on P2VO-induced cognitive deficits is a distinctive pharmacological characteristic of CTS.

Astaxanthin (1), a red-orange carotenoid pigment, is a powerful biological antioxidant that occurs naturally in a wide variety of living organisms. The potent antioxidant property of 1 has been implicated in its various biological activities demonstrated in both experimental animals and clinical studies. Compound 1 has considerable potential and promising applications in human health and nutrition. In this review, the recent scientific literature (from 2002 to 2005) is covered on the most significant activities of 1, including its antioxidative and anti-inflammatory properties, its effects on cancer, diabetes, the immune system, and ocular health, and other related aspects. We also discuss the green microalga Haematococcus pluvialis, the richest source of natural 1, and its utilization in the promotion of human health, including the antihypertensive and neuroprotective potentials of 1, emphasizing our experimental data on the effects of dietary astaxanthin on blood pressure, stroke, and vascular dementia in animal models, is described.

The alteration of the editing pattern of serotonin 2C receptor (5-HT2CR) mRNA has been reported during cell differentiation. Since editing of 5-HT2CR mRNA is regulated by adenosine deaminases acting on RNA (ADARs), it is of interest to investigate if the expression of these enzymes changes during cell differentiation. The level of ADAR1 mRNA in NG108-15 cells was decreased by cell differentiation. These results suggest that the decrease of ADAR1 expression during cell differentiation may play an important role in the differentiation-induced alteration of the 5-HT2CR editing pattern in NG108-15.

Previous studies demonstrated that corymine, an indole alkaloid isolated from the leaves of Hunter zeylanica, dose-dependently inhibited strychnine-sensitive glycine-induced currents. However, it is unclear whether this alkaloid can modulate the function of the N-methyl-D-aspartate (NMDA) receptor on which glycine acts as a co-agonist via strychnine-insensitive glycine binding sites. This study aimed to evaluate the effects of corymine on NR1a/NR2B NMDA receptors expressed in Xenopusoocytes using the two-electrode voltage clamp technique. Corymine significantly potentitated the NMDA-induced currents recorded from oocytes on days 3 and 4 after cRNA injection but it showed no effect when the current was recorded on days 5 and 6. The potentiating effect of corymine on NMDA-induced currents was induced in the presence of a low concentration of glycine (≤0.1 µM). Spermine significantly enhanced the potentiating effect of corymine observed in the oocytes on days 3 and 4, while the NMDA-receptor antagonist 2-amino-5-phosphonopentanone (AP5) and the NMDA-channel blocker 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) reversed the effect of corymine. On the other hand, the nonspecific chloride channel blocker 4,4-di-isothiocyano stilbene-2,2-disulfonoc acid (DIDS) had no effect on the corymine potentiation of NMDA currents. There was no good correlation between corymine- and spermine-induced potentiation of the NMDA-current response in Xenopusoocytes. These results suggest that corymine potentiates the NMDA-induced currents by interacting with a site different from the spermine binding site.

The effects of Uncaria tomentosatotal alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step‐down‐type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training.

The effects of Uncaria tomentosatotal alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training.Uncaria tomentosatotal alkaloid (10–20 mgkg−1, i.p.) and the alkaloid components (10–40 mg kg−1, i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mgkg−1, i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3mgkg−1, i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20mgkg−1, i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mgkg−1, i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mgkg−1, i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mgkg−1, i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam.These results suggest that Uncaria tomentosatotal alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

The modulatory effects of the central noradrenergic and CRF systems on the pentobarbital-induced hypnotic activity were investigated in socially isolated mice. Pentobarbital-induced sleeping time decreased depending on the duration of isolation period and reached the minimum at 4 weeks after the isolation. The intermale aggressive behavior tested in isolated mice increased along with the decrease of hypnotic activity of pentobarbital. I.c.v. injection of CRF (corticotropin-releasing factor; 0.6–2.1 nmol) and i.p. injection of yohimbine (0.5–1 mg/kg), anα2-adrenoceptor antagonist, significantly decreased the pentobarbital-induced sleeping time in group-housed but not in socially isolated mice while α-helical CRF9–41 (αhCRF; 3.3–6.5 nmol i.c.v.), a CRF antagonist, and clonidine (12.5–100 μg/kg i.p. and 7.5–15 nmol i.c.v.), anα2-adrenoceptor agonist, recovered the hypnotic activity of pentobarbital decreased by social isolation to the level in group-housed mice without changing the activity observed in group-housed animals. αhCRF (6.5 nmol i.c.v.) significantly abolished the yohimbine (1 mg/kg i.p.)-induced decrease in the hypnotic activity of pentobarbital in group-housed mice. Propranolol (50–100 nmol i.c.v. and 5–10 mg/kg i.p.), a β-adrenoceptor antagonist, and prazosin (5–10 nmol i.c.v. and 250–500 μg/kg i.p.), anα1-adrenergic antagonist, significantly and dose-dependently recovered the hypnotic activity of pentobarbital in socially isolated mice to the level in group-housed mice. Methoxamine (8–200 nmol i.c.v.), anα1-adrenergic antagonist, as well as CRF decreased the hypnotic activity of pentobarbital in group-housed mice in a dose-dependent manner and the effect of methoxamine was significantly blocked by αhCRF (6.5 nmol i.c.v.) On the other hand, pretreatment with DSP-4 (50 mg/kg i.p.; 3 days before testing), a selective noradrenaline neurotoxin, had no effect on the hypnotic activity of pentobarbital in group-housed or socially isolated mice whereas pretreatment with 6-OHDA and nomifensin (50 μg i.c.v. and 5 mg/kg i.p., respectively, 7 days before testing) significantly prevented the social isolation-induced decrease in the hypnotic activity of pentobarbital without affecting the activity observed in group-housed mice. Both DSP-4 and 6-OHDA treatment decreased noradrenaline (NA) contents in the cerebral cortex by ∼ 80% but the depletion of the hypothalamic NA after 6-OHDA + nomifensin (40–52%) was more marked than that after DSP-4 (22–24%,P < 0.01). These results suggest that the social isolation-induced decrease in the hypnotic activity of pentobarbital involves the hyperactivity of CRF system through NA stimulation ofα1-and/or β-adrenoceptor in mice.

Mechanisms of tryptophan (a 5-HT precursor)-induced changes in body temperature were investigated in rats pretreated with pargyline, a monoamine oxidase inhibitor (MAO-I). Tryptophan (100 mg/kg, IP) did not affect the body temperature in rats, but it produced significant hypothermia followed by marked hyperthermia and higher mortality in the pargyline-pretreated rats. 5-HT depletion with p-chlorophenylalanine (p-CPA, 100 mg/kg/day for 3 days) significantly suppressed not only the body temperature change but also the mortality and 5-HT syndrome following tryptophan plus pargyline administration. Although propranolol (10 mg/kg, IP), a β-adrenoceptor antagonist, did not alter the hypothermia caused by tryptophan in the pargyline-pretreated rats, pindolol (2 mg/kg, SC), a 5-HT1Areceptor and β-adrenoceptor antagonist, suppressed the hypothermia but not the hyperthermia or mortality caused by the same treatment. On the other hand, spiperone and ketanserin, 5-HT2receptor antagonists, at doses of 3 mg/kg, potentiated the hypothermia and completely suppressed the hyperthermia and mortality caused by tryptophan in the pargyline-pretreated rats. These results suggest that tryptophan-induced hypo- and hyperthermia are mediated by 5-HT1Aand 5-HT2receptors, respectively, in the pargyline-pretreated rats.

Effects of Vietnamese ginseng (VG) crude saponin and majonoside-R2, a major saponin constituent, on the psychological stress- and foot shock stress-induced antinociception in the tail pinch test were examined in mice. VG crude saponin (6.2, 12.5, and 25 mg/kg, PO) attenuated psychological stress- but not foot shock stress-induced antinociceptive response, whereas majonoside-R2 (3, 6.2, and 12.5 mg/kg, PO and IP), as well as naloxone (2 mg/kg, IP), suppressed both psychological stress- and foot shock stress-induced antinociception. Pretreatment with the crude saponin (12.5 mg/kg, PO) or majonoside-R2 (6.2 mg/ kg, PO) for 5 days followed by the treatment in combination with stress for next 5 days did not affect the development of adaptation to foot shock stress, but they significantly suppressed the antinociceptive action of the stress measured on the first, second, and third day during the stress exposure period. Majonoside-R2 (6.2 mg/kg, PO) but not the crude saponin (12.5 mg/ kg, PO) significantly blocked the development of adaptation to psychological stress. These results suggest that VG crude saponin has the suppressing effect on psychological stress- and foot shock stress-induced antinociception and that majonoside-R2 is important for the action of the saponin.

The effect of total alkaloid extracted from Peganum harmalaseeds collected in Egypt on body temperature was studied in rats. Intraperitoneal administration of the Peganum harmalaextract produced significant and dose-dependent hypothermia. Similarly, harmine and harmaline, major constituents of the harmala alkaloid, lowered the body temperature. Pretreatment with p-chlorophenylalanine (100 mg/kg/day for 3 days), a 5-HT synthesis inhibitor, significantly attenuated the hypothermic effect of the total alkaloid and harmine, while it tended to block the hypothermic action of harmaline. Methysergide (2 mg/kg), a 5-HT antagonist, significantly attenuated the hypothermia induced by harmala alkaloids. Pindolol (0.05–2 mg/kg), a 5-HT1Areceptor and β-adrenoceptor antagonist, partly blocked the hypothermic effect of the harmala alkaloids in a dose-dependent manner, whereas propranolol (10 mg/kg), a β-adrenoceptor antagonist, failed to alter it, suggesting that β-adrenoceptor is not involved in the hypothermia caused by the alkaloids. Pretreatment with a dopamine receptor antagonist haloperidol (5 mg/kg, SC and 2 mg/kg, IP 24 and 2 h before the experiment, respectively) significantly attenuated the hypothermic effect of harmala alkaloids. Moreover, in haloperidol pretreated rats, methysergide (2 mg/kg, IP) and pindolol (0.05 and 2 mg/kg) completely attenuated the hypothermic effect of the alkaloids. These data suggest that harmala alkaloids produce hypothermic effect mainly through endogenous 5-HT stimulation of 5-HT1Areceptor.

The neuronal damages and the changes in central acetylcholine (ACh) and choline (Ch) contents following permanent occlusion of bilateral common carotid arteries (2VO) of rats were investigated 1 and 4 months after the operation. Two types of neuronal damages were observed in the rats with permanent 2VO. The first type was the infarctions observed in the cerebral cortex and striatum. The infarction in the cortex and striatum was observed in 28.6 and 42.9% of the animals examined 1 month after permanent 2VO, respectively. These ratios did not change even when examined 4 months after permanent 2VO, suggesting that this type of neuronal damage is due to acute ischemic attacks. The second type was progressive neuronal damages observed in the hippocampus and white matter: the neuronal loss in the CA1 subfield appeared 4 months but not 1 month after permanent 2VO and the rarefaction of white matter which was observed 1 months after permanent 2VO and markedly increased 4 months after the operation. Moreover, ACh level significantly decreased in the striatum but not in the cortex, hippocampus or hypothalamus 1 month after permanent 2VO, while the ACh levels in the cortex, striatum and hypothalamus, and Ch levels in all the regions tested significantly decreased when tested 4 months after the operation. These changes did not accompany necrosis. These results suggest that the progressive neuronal degeneration and cholinergic dysfunction following the permanent 2VO are in part involved in chronic cerebral hypoperfusion-induced long-lasting cognition deficits in rats.

Stressful manipulations are known to change the level of neurosteroids capable of interacting with GABAA receptor in the brain. To clarify the involvement of these neurosteroids in social isolation stress-induced decrease in pentobarbital sleep in mice, we examined the effects of 3β-hydroxy-5-pregnen-20-one-3-sulfate (pregnenolone sulfate, PS), a steroidal GABAA antagonist, and 3α,21-dihydroxy-5α-pregnan-20-one (allo-THDOC) and 3α,21-dihydroxy-5β-pregnan-20-one (THDOC), positive allosteric modulators of the GABAA receptor, on the hypnotic activity of pentobarbital in socially isolated mice. Pentobarbital (50 mg/kg, i.p.)-induced sleep was significantly shorter in isolated mice than in group-housed mice and adrenalectomy had no effect on the decrease of pentobarbital sleep following social isolation. PS (5–10 mg/kg, i.p. or 12–24 nmol, i.c.v.) decreased pentobarbital sleep in group-housed mice in a dose-dependent manner without affecting the sleep in socially isolated mice. In contrast, allo-THDOC (14.9–37.4 nmol, i.c.v.) and THDOC (5–12.5 mg/kg, i.p. or 14.9–37.4 nmol, i.c.v.) reversed the pentobarbital sleep decreased by social isolation to the level in group-housed mice. these steroids had no effect on the pentobarbital sleep in group-housed mice. such a reversing effect of THDOC in isolated mice was significantly blocked by PS (24 nmol, i.c.v.). Moreover, i.c.v. injection of yohimbine (30 nmol), methoxamine (200 nmol) and CRF (2.1 nmol) significantly decreased pentobarbital sleep in group-housed mice but not that in isolated mice. The effects of these drugs on pentobarbital sleep in group-housed mice were significantly attenuated by THDOC (12.5 mg/kg, i.p.). These results suggest that changes in the level of neurosteroids with ability to modulate GABAA receptor function are involved in social isolation-induced decrease in the hypnotic activity of pentobarbital in mice.

The effects of N-methyl-d-aspartate NMDA receptor antagonists on scopolamine-induced amnesia and on delay-interposed short-term memory performance were investigated using an 8-arm radial maze in rats. Scopolamine, a muscarinic antagonist, deteriorated the radial maze performance, while MK-801, an NMDA receptor channel blocker and CGS-19755, a competitive NMDA receptor antagonist, showed no obstruction to the spatial cognition in the non-delayed maze task. MK-801(0.01-0.03 mg/kg, i.v.) and CGS-19755 (1–10 mg/kg, i.v.) significantly augmented scopolamine-induced deficit in the non-delayed maze task and impaired the short-term memory in the 5-min delay-interposed task. These results suggest that NMDA antagonists have a negative action on short-term memory and that the interaction between the NMDA and the central muscarinic system plays a role in modulating the cognitive function.

Phytochemical investigation of the CH2C12extract of the Vietnamese medicinal plant Caesalpinia sappanLinn resulted in the isolation of a new cassane-type diterpene named tomocin I (1). Its chemical structure was determined by NMR spectroscopic and mass spectrometric analysis.