Search

We evaluated the effects of pre-germinated brown rice (hatsuga genmai, PGR) on learning and memory and compared them with those of polished rice or cornstarch. In mice that were fed pellets of polished rice or PGR for two weeks, the learning ability in the Morris water maze test was significantly enhanced compared with mice that were fed cornstarch pellets. In the Y-maze test, the intake of food pellets for two weeks failed to affect spontaneous alternation behavior. Beta-amyloid(25-35) (Abeta(25-35): 3 nmol/mouse, i.c.v.) protein impaired spontaneous alternation behavior in mice that were fed pellets of cornstarch or polished rice. In contrast, PGR pellets prevented the Abeta(25-35)-induced impairment of spontaneous alternation behavior. These results suggest that polished rice and PGR have facilitating effects on spatial learning. In particular, it is surmised that PGR may prevent Alzheimer's disease associated with Abeta.

The effects of anticholinergic drugs selective for muscarinic receptor subtypes on prepulse inhibition of acoustic startle response were determined in mice. The prepulse inhibition is associated with sensorimotor information processing in the brain. The anticholinergic agent scopolamine (0.3 mg/kg, s.c.) significantly attenuated prepulse inhibition, while the drug (1-10 mg/kg, s.c.) had no effects on startle amplitude as an indicator of startle response. The muscarinic M(1) receptor antagonist pirenzepine (0.1-10 microg/mouse, i.c.v.) and the muscarinic M(2) receptor antagonist AF-DX116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one) (0.1-10 microg/mouse, i.c.v.) had no effects on prepulse inhibition or startle amplitude. The muscarinic M(3) receptor antagonist 4-DAMP (1,1-dimethyl-4-diphenylacetoxy-piperidinium iodide) (30 microg/mouse, i.c.v.) and the muscarinic M(4) receptor antagonist tropicamide (0.1 microg/mouse, i.c.v.) significantly attenuated prepulse inhibition, while tropicamide (0.01 microg/mouse, i.c.v.) but not 4-DAMP (10 and 30 microg/mouse, i.c.v.) produced a significant increase in startle amplitude. These results suggest that the blockade of muscarinic M(3) and M(4) receptors leads to the disruption of prepulse inhibition.

Nociceptin (also called orphanin FQ) is an endogenous heptadecapeptide that activates the opioid receptor-like 1 (ORL1) receptor. Nociceptin system not only affects the nociception and locomotor activity, but also regulates learning and memory in rodents. We have previously reported that long-term potentiation and memory of ORL1 receptor knockout mice are enhanced compared with those in wild-type mice. Here, we show the neuronal mechanism of nociceptin-induced modulation of learning and memory. Retention of fear-conditioned contextual memory was significantly enhanced in the ORL1 receptor knockout mice without any changes in cued conditioned freezing. Inversely, in the wild-type mice retention of contextual, but not cued, conditioning freezing behavior was suppressed by exogenous nociceptin when it was administered into the cerebroventricle immediately after the training. ORL1 receptor knockout mice exhibited a hyperfunction of N-methyl-D-aspartate (NMDA) receptor, as evidenced by an increase in [3H]MK-801 binding, NMDA-evoked 45Ca2+ uptake and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity and its phosphorylation as compared with those in wild-type mice. The NMDA-induced CaMKII activation in the hippocampal slices of wild-type mice was significantly inhibited by exogenous nociceptin via a pertussis toxin-sensitive pathway. However, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor GluR1 subunit at Ser831 and Ser845, and NMDA receptor subunit NR2B at Thr286 were phosphorylated similarly after NMDA receptor stimulation in both type of mice. The expressions of GluR1 and GluR2 also did not change, but the levels of polysialylated form of neuronal cell adhesion molecule (N-CAM) were reduced in the ORL1 receptor knockout as compared with wild-type mice. These results suggest that nociceptin system negatively modulates learning and memory through the regulation of NMDA receptor function and the expression of N-CAM.

In the present study, we investigated how the neurosteroid, dehydroepiandrosterone sulfate (DHEAS) affects the development of morphine dependence and tolerance in mice. Mice administered morphine (10 mg/kg) twice a day for 5 days developed tolerance to the analgesic effect and dependence as shown by a severe withdrawal syndrome induced by naloxone. Co-administration of DHEAS (10 mg/kg) with morphine significantly inhibited the development, but not the expression, of tolerance to morphine-induced analgesia and the naloxone-precipitated withdrawal. The expression of c-fos mRNA was observed in the frontal cortex and thalamus of mice showing signs of naloxone-precipitated withdrawal, while the expression of c-fos mRNA was significantly diminished by co-administration of DHEAS with morphine. On the naloxone-precipitated withdrawal, mice showed a significant elevation of cyclic AMP (cAMP) levels in the thalamus, whereas chronic administration of DHEAS with morphine did not affect the increase in cAMP. Interestingly, repeated co-administration of DHEAS with morphine prevented the withdrawal-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 2 in the frontal cortex. These results showed that DHEAS prevented the development of morphine tolerance and dependence and suggested that the attenuating effects of DHEAS might result from the regulation of c-fos mRNA expression, which is possibly involved the signaling activation of ERK, but not of cAMP pathway.

The effects of microinjection of phencyclidine (PCP) and dizocilpine, non-competitive NMDA receptor antagonists, and dopamine into the nucleus accumbens were examined in rats trained to discriminate PCP (1.5 mg/kg i.p.) from saline under a two-lever fixed ratio 20 schedule of food reinforcement. Microinjection of PCP (2-40 microg) and dizocilpine (2-12 microg) into the bilateral nucleus accumbens produced a dose-dependent increase in PCP-appropriate responding and fully substituted for systemically administered PCP, whereas microinjection of dopamine (1-4 microg) did not produce PCP-like discriminative stimulus effects. The performance of PCP discrimination was assessed after bilateral destruction of the dopaminergic nerve neurons in the nucleus accumbens with dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA, 4 microg/1 microl/side). The destruction of dopaminergic nerve neurons in the nucleus accumbens failed to prevent the performance of PCP discrimination. There was no difference in the average percentages of PCP-appropriate responding between vehicle and 6-OHDA-treated rats in the dose-response tests. These results suggest that the dopaminergic system in the nucleus accumbens does not play a critical role in the discriminative stimulus effects of PCP.

The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.

The effect of phencyclidine (PCP) on latent learning was investigated using a one-trial water-finding task in mice. Mice without water deprivation were given PCP or saline before a training trial, which consisted of exposure to a novel open-field environment with an alcove containing a water tube. Twenty to twenty-four hours after water deprivation, animals were placed in the same apparatus and the time required to find the water tube measured (test trial). Saline-treated trained mice showed a significantly shorter time to find the water tube during the test trial (finding latency) than naive mice that had not been trained. When PCP (1mg/kg i.p.) was administered before the training trial, the finding latency was significantly prolonged in comparison with that in the saline-treated mice, indicating that PCP induced impairment of latent learning. 1-(3,4-Dimethoxy-phenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503: 0.3 mg/kg s.c.) and (+)-pentazocine (1 mg/kg s.c.), selective sigma(1) receptor agonists, or D-cycloserine (10 and 30mg/kg, s.c.), a glycine binding site agonist, significantly counteracted the PCP-induced impairment of latent learning, whereas (+)-SKF-10,047 (0.1-3 mg/kg s.c.), a putative sigma(1) receptor agonist, did not. The ameliorating effects of SA4503 and (+)-pentazocine were antagonized by N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy) phenyl) ethylamine (NE-100: 1 mg/kg i.p.), a selective sigma(1) receptor antagonist. SA4503 also ameliorated the impairment of latent learning induced by dizocilpine, a non-competitive N-methyl-D-aspartate receptor antagonist, the effect being antagonized by NE-100. These results suggest that PCP induces an impairment of latent learning, this effect being mediated via glutamatergic systems, and that activation of sigma(1) receptors ameliorates impairment of latent learning induced by PCP.

The effects of several N-methyl-D-aspartate (NMDA) receptor- and sigma receptor-related compounds on the discriminative stimulus effects of phencyclidine (PCP) were examined in rats trained to discriminate PCP (1.5 mg/kg, i.p.) from saline under a two-lever fixed ratio 20 schedule of food reinforcement. PCP produced a dose-dependent increase in PCP-appropriate responding. A non-competitive NMDA receptor antagonist, dizocilpine (0.2 mg/kg, i.p.) and a putative sigma(1) receptor agonist, (+)-SKF-10047 (10 mg/kg, i.p.) fully substituted for PCP in every rat tested. Neither a competitive NMDA receptor antagonist, CGS-19755 (0.1-3 mg/kg, i.p.), sigma(1) receptor agonist, (+)-pentazocine (10-30 mg/kg, i.p.) nor dextromethorphan (10-20 mg/kg, i.p.) produced PCP-like discriminative stimulus effects. The discriminative stimulus effects of PCP (1.5 mg/kg, i.p.), dizocilpine (0.2 mg/kg, i.p.) and (+)-SKF-10047 (10 mg/kg, i.p.) were significantly attenuated by CGS-19755 (1 mg/kg, i.p.), but not by sigma(1) receptor antagonist BMY-14802 (10 mg/kg, i.p.) and NE-100 (5 mg/kg, i.p.). These results suggest that the discriminative stimulus effects of PCP are predominantly mediated via PCP binding sites on the NMDA receptor-ion channel complex, not via sigma(1) receptors. In addition, the PCP-like discriminative stimulus effects of (+)-SKF-10047 were demonstrated to be mediated via PCP binding sites.

We investigated the effect of rolipram, a selective phosphodiesterase IV inhibitor, on morphine dependence in mice. The withdrawal manifestations were significantly reduced in mice that were treated with rolipram in combination with morphine repeatedly, compared to the mice treated with morphine and saline. Immunohistochemical study of c-Fos protein revealed a significant increase in the protein expression, 1 h after naloxone induced withdrawal manifestations. A combination of rolipram and morphine treatment for 5 days prevented the increase of c-Fos protein expression. Acute rolipram treatment prior to the naloxone challenge had no effect. Repeated treatment with rolipram itself had no effect either on behavior, or on c-Fos protein expression. These results suggest that chronic rolipram treatment in combination with morphine in mice will abolish the development of morphine dependence and the expression of c-Fos protein induced by naloxone challenge.

Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor knockout mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor knockout mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor knockout mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor knockout mice, the jumping signs in the nociceptin receptor knockout mice were less severe than those in wild-type mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor knockout mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor knockout mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.

Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines that are considered to be involved in a variety of neuropsychiatric functions. Here, we report behavioral and neuropsychological deficits in mice carrying a single mutated allele of the TH gene in which TH activity in tissues is reduced to ∼40% of the wild-type activity. In the mice heterozygous for the TH mutation, noradrenaline accumulation in brain regions was moderately decreased to 73–80% of the wild-type value. Measurement of extracellular noradrenaline level in the frontal cortex by the microdialysis technique showed a reduction in high K+-evoked noradrenaline release in the mutants. The mutant mice displayed impairment in the water-finding task associated with latent learning performance. They also exhibited mild impairment in long-term memory formation in three distinct forms of associative learning, including active avoidance, cued fear conditioning, and conditioned taste aversion. These deficits were restored by the drug-induced stimulation of noradrenergic activity. In contrast, the spatial learning and hippocampal long-term potentiation were normal in the mutants. These results provide genetic evidence that the central noradrenaline system plays an important role in memory formation, particularly in the long-term memory of conditioned learning.

Mice infected with an immunosuppressive murine leukemia virus mixture, LP-BM5 show a profound immunosuppression described as murine acquired immune deficiency syndrome (AIDS). In the present study, we characterized learning and memory deficits in C57BL/6 mice infected with LP-BM5. Spontaneous alternation behavior in a Y-maze and latent learning (spatial attention) in a water-finding test, as well as spatial reference and reversal learning in a water maze test, were significantly impaired in the mice infected with LP-BM5. These deficits appeared in the absence of any motoric and visual impairment as assessed by open-field, rotarod and visual water maze tests. These results suggest that cognitive functions are impaired in the mice infected with LP-BM5. Furthermore, LP-BM5-infected mice may be useful as a model for the AIDS dementia complex.

We isolated genes for the opioid receptor homologue MOR-C, namely nociceptin receptor (designated alternatively as orphanin FQ receptor) and generated nociceptin receptor-knockout mice. Previously, we have reported that the nociceptin system appears to participate in the regulation of the auditory system. However, the behavior of the nociceptin receptor-knockout mice has yet to be fully characterized. In the present study, we investigated changes in several behavioral performances in mice which lack nociceptin receptor. Nociceptive thresholds of nociceptin receptor-knockout mice were unchanged in the hot-plate and electric foot-shock tests as well as tail-flick and acetic acid-induced writhing tests compared to those of wild-type mice. The nociceptin receptor-knockout mice did not show any behavioral changes in the elevated plus-maze task. Surprisingly, in the water-finding test, the nociceptin receptor-knockout mice showed an enhanced retention of spatial attention (latent learning) compared to wild-type mice. In a biochemical study, dopamine content in the frontal cortex was lower in nociceptin receptor-knockout mice than wild-type mice. These results suggest that nociceptin receptor plays an important role in spatial attention by regulating the dopaminergic system in the brain.

We have previously found that repeated phencyclidine (PCP) treatment enhances the immobility induced by forced swimming and suggested that this behavioral change could be used as a model of the negative symptoms, particularly depression, of schizophrenia. The present study attempted to examine the effects of antidepressants on the depressive states (immobility) induced by forced swimming in mice repeatedly treated with PCP, compared with those in mice repeatedly treated with saline. In mice repeatedly treated with saline, desipramine (5 and 10 mg/kg) and imipramine (5 and 10 mg/kg) significantly attenuated immobility, whereas mianserin (5-20 mg/kg) and clomipramine (10 and 50 mg/kg) had no affect. In mice repeatedly treated with PCP, the enhancing effect of PCP on immobility was attenuated by mianserin (5-20 mg/kg) at doses which did not have any effect in saline-treated mice, and by desipramine at higher doses (20 and 50 mg/kg). However, imipramine (5-20 mg/kg) and clomipramine (10-50 mg/kg) did not affect PCP-induced enhancement of immobility. In the biochemical study, the content of 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA/5-hydroxytryptamine (5-HT) ratio in the prefrontal cortex in mice repeatedly treated with PCP, but not with saline, following the forced swimming test were significantly increased, compared with those in the corresponding control mice (which did not perform the test). The present findings suggest that the depressive states induced by the forced swimming in mice repeatedly treated with PCP are less sensitive to acute treatment with tricyclic antidepressants, and this may be due to increase in 5-HT turnover. Antidepressants such as mianserin, which have the 5-HT2 receptor antagonist properties, may be useful for the treatment of negative symptoms of schizophrenia.

The activation of N -methyl- d -aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N -methyl- d -aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo , although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, N G -nitro- l -arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non-competitive N -methyl- d -aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both N G -nitro- l -arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. N G -Nitro- l -arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of N G -nitro- l -arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with l -arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, N G -nitro- l -arginine methyl ester, or 7-nitro indazole. Neither N G -nitro- l -arginine methyl ester nor l -arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.

We have observed an excess specific heat for solid 3 He in silver sinter from melting pressure to 55 bar below a few tens of mK. The excess specific heat is nearly independent of temperature. Except for the solid near the melting pressure, the magnitude of the excess specific heat is almost constant throughout a wide pressure region. This fact is explained in terms of the presence of about two layers of amorphous surface solid 3 He on the heterogeneous silver-sinter substrate.

We have measured the AC magnetic susceptibility of single crystals of the heavy fermion compounds CeCu6 and CeNi at temperatures down to 250 μK . The susceptibility of CeCu6 shows a peak at about 2 mK in a zero magnetic field. The peak height along a-axis is about 10 times as large as along b- and c-axis, and decreases to zero in increasing field up to 11 mT. It is likely that the susceptibility of CeNi along c-axis has three peaks: below 350 μK , at 47 mK and at 0.3 K, respectively. The two peaks at lower temperatures are suppressed by a magnetic field. The newly observed peaks in the susceptibilities for CeCu6 and CeNi suggest effects of magnetic impurities rather than of magnetic ordering.

BackgroundEpidemiological studies suggest that radiation exposure may be a potential risk factor for schizophrenia in adult humans. Here, we investigated whether adult irradiation in rats caused behavioral abnormalities relevant to schizophrenia.Methodology/principal findingsA total dose of 15-Gy irradiation in six fractionations during 3 weeks was exposed to the forebrain including the subventricular zone (SVZ) and subgranular zone (SGZ) with male rats in the prone position. Behavioral, immunohistochemical, and neurochemical studies were performed three months after fractionated ionizing irradiation. Three months after fractionated ionizing irradiation, the total numbers of BrdU-positive cells in both the SVZ and SGZ zones of irradiated rats were significantly lower than those of control (sham-irradiated) rats. Hyperactivity after administration of the dopaminergic agonist methamphetamine, but not the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine, was significantly enhanced in the irradiated rats although spontaneous locomotion in the irradiated rats was significantly lower than that of controls. Behavioral abnormalities including auditory sensory gating deficits, social interaction deficits, and working memory deficits were observed in the irradiated rats.Conclusion/significanceThe present study suggests that irradiation in adulthood caused behavioral abnormalities relevant to schizophrenia, and that reduction of adult neurogenesis by irradiation may be associated with schizophrenia-like behaviors in rats.

Background: Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. However, its in vivo function has not been clarified. Results: Knockout mice lacking the MK gene (Mdk) showed no gross abnormalities. We closely analysed postnatal brain development in Mdk(–/–) mice using calcium binding proteins as markers to distinguish neuronal subpopulations. Intense and prolonged calretinin expression was found in the dentate gyrus granule cell layer of the hippocampus of infant Mdk(–/–) mice. In infant Mdk(+/+) mice, calretinin expression in the granule cell layer was weaker, and had disappeared by 4 weeks after birth, when calretinin expression still persisted in Mdk(–/–) mice. Furthermore, 4 weeks after birth, Mdk(–/–) mice showed a deficit in their working memory, as revealed by a Y-maze test, and had an increased anxiety, as demonstrated by the elevated plus-maze test. Conclusion: Midkine plays an important role in the regulation of postnatal development of the hippocampus.

We have measured the AC nonlinear susceptibilities λ3 of RDP(RbH2PO4)-ADP(NH4H2PO4) proton glasses above and below the glass transition temperature (13 K). For the ADP concentration x, 0.22 < x < 0.8, the mixed crystals take up a frozen random configuration of electric dipoles and the dielectric susceptibility shows the presence of two-level systems. We report for the first time the strong temperature depedence of λ3 of proton glasses similar to that of the spin glasses at the glass transition temperature.

The nonlinear dielectric constant of the RDP(RbH2PO4)-ADP(NH4H2PO4)proton glass has been measured down to 0.03 K. For the ADP concentration x. 0.22

Theories predict that spontaneous magnetization occurs in the superconducting B phase in UPt3 because of broken time-reversal symmetry. The strength of the spontaneous magnetization depends on whether it comes from spin degeneracy or orbital degeneracy. We measured the internal field due to the spontaneous magnetization on the supercondicting transition to the B phase for a UPt3 sample in the magnetic fields very close to zero, using a SQUID magnetometer. The upper limit of the spontaneous internal field was 0.007 gauss. This result seems to favor the theory of the orbital degeneracy.

The nuclear spins in hcp solid3He with a molar volume of 19.3 cm3 whose ordering temperature was estimated to be on the order of 10 μK, was cooled by the method of two-stage demagnetization. Solid3He was precooled down to below 1 mK in the magnetic field of 2 T by using the first stage that was composed of a copper bundle of 147 moles. Then solid3He of 0.002 mole in the pores of a silver sponge was demagnetized down to 0.01T using the Kapitza resistance on the silver interface as a thermal switch. There was a pressure decrease of 60 Pa during and after demagnetization with no significant signature of nuclear ordering. There was an appreciable change in the magnetic susceptibility in a separate cell after demagnetization with no signature of ordering as well.

The nonmetallic susceptibility cell using Stycast 1264 is described. It withstood pressure up to 25 MPa at low temperature. The tensile strength of Stycast 1264 at room temperature was measured to be 56.0 MPa.

We have measured pressure vs temperature for 3 He in sintered silver below pressure of 20MPa and in the temperature range between 1.2 and 4.2K. The sintered silver has pores of 280nm in diameter. We also measured pressure for bulk 3 He in a separate cell simultaneously. 3 He in the sintered silver with molar volume more than 19.3 cm 3 shows pressure drop less than the corresponding drop in bulk solid at the bcc-hcp transformation. This means that the sample in the present sinter is not a perfect hcp crystal for molar volume more than 19.3 cm 3 . We report the behavior of solid 3 He in the sinter which is different from that of bulk solid.

Pressure measurements have been made in hcp solid3He down to 1 mK in magnetic fields up to 0.16 T and for molar volumes of 18.90, 19.16, and 19.45 cm3/mol. The measurements show that the pressure in magnetic fields is thermodynamically consistent with reported values for the Weiss temperature deduced from nuclear magnetization. The pressure at zero field, however, has smaller volume dependence than the pressure in magnetic fields.

The dielectric constant of a mixed crystal of hydrogenbonded ferroelectrics RbH2PO4(RDP) and antiferroelectrics NH4H2PO4(ADP) has been measured down to 0.025 K. For the ADP concentration x ranging 0.22

A double stage nuclear demagnetization cryostat has been constructed to study the nuclear magnetic ordering of hcp solid 3 He. The first nuclear stage of this cryostat was machined from a copper block (99.999 purity, RRR 2700), and the amount of copper is effectively 64.6 moles in a 8T field. We used indium (RRR 11300) for the heat switch above this stage. Solid 3 He for the second nuclear stage is precooled in a magnetic field up to 7.2T. The second stage is equipped with ac susceptibility, NMR and pressure cells to measure nuclear magnetic ordering of hcp solid 3 He.

We have measured the electrical resistivity of La 4 BaCu 5 O 13 and La 5 SrCu 6 O 15 -based compounds down to 39mK and 16mK, respectively, without observing superconductivity. When the resistivity ϱ − ϱ 0 was proportional to T γ , the exponent γ ranged from 1.18 to 1.83 for these compounds, where ϱ 0 is residual resistivity and T is temperature. It was ascertained from our measurements down to the mK range that these compounds were not superconducting because of a three-dimensional network of CuO 5 units.

A combination of a lock-in amplifier and a constant current supply is presented as an alternative for monitoring resistance thermometers in a dilution refrigerator. This apparatus has performance comparable to the resistance bridge and is less expensive.

We have precisely measured the magnetization and ac susceptibility of hcp solid 3He as a function of molar volume in the temperature range down to 38 uK. We have obtained the Weiss temperature and the next higher order term in the high temperature expansion in magnetization at lower temperatures. The obtained molar volume dependence of the Weiss temperature is in good agreement with that of the bcc phase, though the sign of the Weiss temperature is opposite. The susceptibility data are discussed associated with the exchange-Zeeman relaxation time.

The thermodynamic pressure has been measured in hcp solid 3He at molar volumes from 18.63 cm3/mole to 19.37 cm3/mole and for temperatures from 8 mK to 0.93 mK. The exchange contribution to the pressure is observed and compared to the expression of the high-temperature series expansion of the spin Hamiltonian including two- and three-particle exchange.

Morphine is the most potent opioid analgesic currently available and its use is increasing for treatment of severe pain, however, long-term morphine exposure induces physical dependence/tolerance. Although the mechanisms underlying this phenomenon have not been established, several biochemical changes including intracellular cAMP systems and Ca2+ mobilization have been suggested. To evaluate the contribution of cAMP, we investigated the effects of nefiracetam [N-(2,6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl)acetamide] and phosphodiesterase inhibitors (theophylline, enprofylline and rolipram) on the development of morphine dependence/tolerance. Mice administered morphine (6 or 10 mg/kg, s.c.) twice daily for 5 days, showed withdrawal signs (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg/kg, i.p.), indicating the physical dependence to morphine. Further, the tolerance to antinociceptive effect of morphine was observed in these mice on the tail-flick test. However, coadministration of nefiracetam (5 or 10 mg/kg, p.o.), enprofylline (30 mg/kg, p.o.) and rolipram (0.3 or 1 mg/kg, i.p.) with morphine during the pretreatment period, significantly reduced the withdrawal signs, moreover, the tolerance was significantly attenuated. Acute administration of nefiracetam failed to reduce the withdrawal signs and did not affect the antinociceptive effect of morphine in morphine-naive mice. Theophylline (3 or 10 mg/kg, p.o.) tended to attenuate the development of morphine dependence/tolerance. The present findings suggest that coadministration of compounds which increase cAMP level with morphine may be a useful strategy to attenuate the development of morphine dependence/tolerance in the clinic.

Thermal conductivity measurements on single crystal niobium specimens of resistivity ratios 6300 and 2500 are reported as a function of magnetic fields. The measured thermal conductivity varies linearly with H c2 – H in fields very close to H c2 and approximately with ( H c2 - H ) 1/2 in slightly lower fields, as predicted by the Houghton-Maki (HM) theory. Experimental results on Nb6300 in longitudinal fields agree with the HM theory using the density of states N (0)=2.3×10 36 cm -3 erg -1 at lower temperatures (\(T{\lesssim}3\) K) whereas at higher temperatures (\(T{\gtrsim}4\) K) they do not agree with the theory. Experimental data on Nb6300 in transverse fields cannot be explained by the theory with the same N (0) as in the longitudinal case, even at low temperatures. The field coefficients of the thermal conductivity do not show the purity dependence in our specimens investigated.

Low temperature specific heat and electrical resistivity of isoelectronic CrMo alloys containing up to 36.6 atomic % Mo were measured in order to study spin density wave (SDW) magnetism. Linear specific heat coefficient increases with Mo concentration and goes through a maximum, where SDW vanishes. The relation between linear specific heat coefficient and Neel temperature is discussed in reference to a recent spin fluctuation theory introduced into itinerant antiferromagnetism.

An automated system using an 8 bit microcomputer which controls a nuclear demagnetization refrigerator is described. The microcomputer is employed for controlling temperature, reading data from experimental apparatus storing data on a magnetic tape cassette and transferring data to a computer in a computation centre by a telephone. The detailed circuitries of an interface of an NMR thermometer and a voltage sweep device are also described.

The new measurement of the specific heat of bcc 5d transition metal alloys of Ta-Re series containing up to 40 atomic % of Re has been made and their superconducting behaviours of the alloys including up to 20 atomic % of Re have been studied. By making use of McMillan's theoretical treatment, the electron-phonon coupling constant and bare electronic density of states were deduced. The electron-phonon coupling constant, as a function of the number of electrons per atom, bahaves in the same way as the density of states. This result suggests that the coupling constant is proportional to the bare density of states. The present results of the density of states were compared with the theoretical ones which were deduced by Mattheiss for Ta and W.