Cyclosporin A Treatment in Intrinsic Canine Atopic Dermatitis (Atopic-like Dermatitis): Open Trial Study.

In this study, dogs were separated into two groups and treated with immunosuppressant (Cyclosporin A: CsA). The first group was the canine atopic dermatitis (CAD) group, which is similar to extrinsic atopic dermatitis (AD) in humans (treated with a CsA dose of 2.5-5.5 mg/kg, n=8), and the second group was the canine atopic-like dermatitis (ALD) group, which is similar to intrinsic AD in humans (treated with a CsA dose of 2.5-6.5 mg/kg, n=14). The canine atopic dermatitis extent and severity index (CADESI)-4 was evaluated before treatment (PRE) and after treatment (POST) to assess the effectiveness of CsA for the two groups. In the CAD group, CADESI-4 showed no change (PRE:79±29, POST:77±28) and out of the eight dogs, no dogs showed complete remission, three dogs showed partial remission, and five dogs showed no effect. Whereas in the ALD group, CADESI-4 showed a significant reduction (PRE: 61±42, POST: 32±25, p<0.01) and out of the 14 dogs, 11 dogs showed complete remission, two dogs showed partial remission, and one dog showed no effect. The results indicate that the immunosuppressant showed effectiveness for the dogs diagnosed with ALD. One dog had to be treated for a year and eight months, which was the longest period in the study, this dog presented with hyperplasia of the lymphoidgland and mammary tumor.

Rush sublingual immunotherapy in canine atopic dermatitis: a prospective pilot study.

Twenty dogs with canine atopic dermatitis (CAD) were treated with rush sublingual immunotherapy (SLIT), with a 48 hour build-up phase and 6 months maintenance phase (treated by antigen once every 3-4 weeks). The canine atopic dermatitis extent and severity index (CADESI)-4 was evaluated before treatment (baseline) and after 6 months. An open, non-controlled, non-randomized pilot trial was conducted to assess the effectiveness and safety of rush SLIT for environmental allergen extracts (Dematophagoides pteronyssinus and D.farinae mix and other). Three dogs dropped out and 17 dogs finished the trial. CADESI-4 at baseline was 60.6±27.1 (range 17-107, n=17). After 6 months of SLIT treatment, CADESI-4 was 37.4±36.0 (range 5-152, n=17) (p<0.01), which was a 38.3% reduction. A significant improvement, defined as a CADESI-4 reduction of >30%, was observed in 13 out of 17 dogs (76%). A moderate improvement, defined as a CADESI-4 reduction of ≦30%, was observed in 2 dogs (12%). In the other 2 dogs (12%), CADESI-4 worsened or showed no change. However, no severe adverse effects were observed during the trial. Therefore, rush SLIT against environmental allergen extract for CAD showed effectiveness and safety as evidenced by the reduction of CADESI-4 after 6 months SLIT without severe adverse effects.

Fluoxetine (SSRI) treatment of canine atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover trial.

This study investigated effects of a fluoxetine (selective serotonin reuptake inhibitors; SSRI, 1 mg/kg) on pruritus in canine atopic dermatitis (CAD). After 4-weeks of base-line observation, 8 dogs with CAD entered a 2-months randomized, double-blind, placebo-controlled, crossover trial comparing fluoxetine with placebo. Clinical efficacy was evaluated using a Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) and Pruritus Visual Analog Scale (PVAS). Six dogs completed the study [two out of eight dogs (both of them were Shiba Inu) dropped out from the study due to a depression]. CADESI-03 and PVAS between fluoxetine and placebo showed no significant difference statistically (P > 0.05 and P > 0.05 respectively). Fluoxetine showed no efficacy on pruritus in CAD. Further researches are needed for the treatment on pruritus of CAD.

Accuracy of pre- and postcontrast 3D time-of-flight MR angiography in patients with acute ischemic stroke: correlation with catheter angiography.

BACKGROUND AND PURPOSE: 3D time-of-flight (TOF) MR angiography (MRA) is insensitive to slow flow; however, the use of MR imaging contrast agents helps to visualize slow-flow vessels and avoids overestimation of vascular occlusion. The purpose of this study was to correlate pre- and postcontrast 3D TOF MRA with the results of conventional angiography during endovascular reperfusion therapy and to determine the accuracy of postcontrast 3D TOF MRA. MATERIALS AND METHODS: Thirteen patients who underwent endovascular reperfusion therapy for acute ischemic stroke were retrospectively analyzed. MR imaging techniques included single-slab 3D TOF MRA with and without contrast, as well as perfusion-weighted imaging. Angiography during reperfusion therapy was used as a standard of reference. Affected arteries were divided into segments either proximal or distal to the lesion, and pre- and postcontrast MRA signals were graded as absent, diminished or narrowed, or normal. RESULTS: In 2 of 5 patients with arterial stenosis and 6 of 8 patients with complete occlusion, MRA signal intensity proximal to each lesion was absent, indicating a proximal pseudo-occlusion on precontrast MRA. Postcontrast MRA demonstrated an arterial signal intensity proximal to the stenotic or occlusive lesions in all 13 patients. Arterial signal intensity distal to the occlusion was identified on postcontrast MRA in 7 of 8 patients having complete occlusion, and the extent of occlusion on postcontrast MRA was similar to results of conventional angiography. CONCLUSION: In this small series, postcontrast 3D TOF MRA more accurately delineated the extent of stenotic or occlusive arterial lesions than precontrast MRA.

Three-dimensional fast recovery fast spin-echo imaging of the inner ear and the vestibulocochlear nerve.

The aim of this study was to assess the performance of three-dimensional fast recovery fast spin-echo (3DFRFSE) for imaging of the inner ear as well as the facial and vestibulocochlear nerves. We evaluated 3DFRFSE sequences, comparing it with 3D fast spin-echo (3DFSE) in a water phantom and in 12 normal volunteers. We also examined 66 patients using 3DFRFSE sequence and assessed the visualization of their pathologies. In a water phantom study, signal intensity (SI) on 3DFRFSE was higher than that on 3DFSE at the same TR ranging from 1,500 to 6,000 ms. In normal volunteers, 3DFRFSE with TR of 2,800 ms showed comparable SI, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) superior to those on 3DFSE with TR of 5,000 ms. In clinical setting, 3DFRFSE was useful in demonstrating anatomic details in the labyrinth and pathologic findings of inner ear. The 3DFRFSE can provide high-resolution heavily T2-weighted images (T2WI) with shorter scan time than 3DFSE without significant disadvantage. The 3DFRFSE is a beneficial technique for evaluation of lesions in the inner ear as well as the facial and vestibulocochlear nerves.

Development of obesity and neurochemical backing in aurothioglucose-treated mice.

To clarify the neurochemical backing of aurothioglucose (ATG)-induced obesity in mice, we investigated lesion sites, hypothalamic neurotransmitters and c-Fos-like immunoreactivity (Fos-IR). At day 2 after ATG, tissue loss or cells death was observed in several parts of the ventral area of the ventromedial hypothalamic nucleus (VMH), and the dorsal area of arcuate nucleus and in the nucleus of the solitary tract (NTS). However, the greater part of the VMH was retained. Body weight began to increase in week 1. Hypothalamic serotonin (5-HT) and the metabolites were increased at day 2. The contents of acetylcholine, norepinephrine and dopamine in the hypothalamus showed no significant change. In week 1, the area shown tissue loss was compacted and plugged up. In the control group, most obvious c-Fos-like immunoreactive region was paraventricular nucleus (PVN). At day 2, Fos-IR was observed around destroyed regions in the hypothalamus and NTS, but few Fos-IR was found in the other regions including PVN. The Fos-IR around destroyed regions diminished after week 1. In week 3, Fos-IR in the PVN increased. These results suggest that the development of ATG-induced obesity cannot be attributed to solely VMH destruction. The restoration processes of the neuronal dysfunction involving PVN seem to play an important role in the development of obesity. NTS lesion and 5-HT system might contribute to decrease in food intake for several days after ATG.

Differentiation between high-grade glioma and metastatic brain tumor using single-voxel proton MR spectroscopy.

The purpose of this study was to clarify the efficacy of single-voxel proton magnetic resonance spectroscopy (MRS) in differentiating high-grade glioma from metastasis. Thirty-one high-grade gliomas (11 anaplastic gliomas and 20 glioblastomas) and 25 metastases were studied. Proton MRS was performed using point-resolved spectroscopy with echo times (TEs) of both 136 and 30 ms. The peaks for lipid were evaluated at short TE, and those for N-acetyl-aspartate (NAA), creatine (Cr), and choline-containing compounds (Cho) were assessed at long TE. All the tumors exhibited a strong Cho peak at long TE. Twenty-one of 25 metastases showed no definite Cr peak. The remaining 4 metastases showed NAA and Cr peaks; however, the presence of NAA and relatively high NAA/Cr ratio (1.58+/-0.56) indicated normal brain contamination. All the gliomas, except for a single glioblastoma, showed a Cr peak with (n=16) or without (n=14) NAA. At short TE all metastases and glioblastomas showed definite lipid or lipid/lactate mixture, but anaplastic gliomas showed no definite lipid signal. Intratumoral Cr suggests glioma. Absence of Cr indicates metastasis. Definite lipid signal indicates cellular necrosis in glioblastoma and metastasis, and no lipid signal may exclude metastases.

Cholinergic input to the supraoptic nucleus increases Fos expression and body temperature in rats.

To examine the role played by cholinergic input and processes in the supraoptic nucleus (SON) in the control of body temperature and water intake in rats, we used microdialysis to stimulate and analyze SON without disturbing the behavior of unanesthetized rats. After microdialysis, we also investigated immunoreactivity for c-Fos protein in the brain as an index of neuronal activation. Stimulation with neostigmine, an acetylcholine esterase inhibitor, through the microdialysis probe increased the extracellular concentration of acetylcholine in the SON. This cholinergic stimulation dose-dependently increased body temperature but did not significantly change the water intake. The stimulation markedly increased c-Fos-like immunoreactivity (Fos-IR) in the SON and certain hypothalamic areas, including the paraventricular nucleus (PVN) and median preoptic nucleus (MnPO). Fos-IR was also evident in certain regions of the pons and brainstem, including the locus ceruleus (LC), area postrema (AP), and nucleus of the solitary tract (NTS). Addition of atropine, a muscarinic receptor antagonist, to the dialysis medium containing neostigmine attenuated the increase of Fos-IR and suppressed the neostigmine-induced responses in body temperature. These results suggest that cholinergic input and activation of the muscarinic cholinoceptive neurons in the SON contribute to the regulation of body temperature. Activation of noradrenergic pathways in the brainstem including LC and NTS may be involved in the thermoregulation mechanism.

Hypothalamic neuroactivity in specific processes and central regulation of body temperature and water intake.

The method described was designed to elucidate the role of a particular neuronal system or specific nucleus in the central nervous system (CNS) in controlling physiological and biological functions. The neurochemical aspects of the CNS regulatory mechanism and related networks remain to be further investigated. There is little information available about the relationship between neuroactivity in the specific brain nuclei and physiological or biological responses in mammals. An adequate analysis of this relationship provides valuable insight to clarify which nucleus and what types of neurons are truly involved in the excitation of physiological events and its regulation. In the present study, we used microdialysis for stimulation of the anterior hypothalamus (AH) and simultaneous analysis of cholinergic activity, and we investigated c-Fos-like immunoreactivity (Fos-IR) in the brain in the same animal following microdialysis. The nuclear protein c-Fos, the product of c-fos oncogene, has been used as a marker of neuronal activity at the cellular level in the brain. Various physiological and pharmacological stimuli have been shown to induce Fos-IR in specific neuronal populations located in various regions of the brain. However, there are few studies investigating the responses produced by c-Fos expression in specific regions in same animals. We showed the involvement of hypothalamic cholinergic mechanisms in the thermoregulatory and water regulatory processes using the above procedures.

Opposite regulation of body temperature by cholinergic input to the paraventricular nucleus and supraoptic nucleus in rats.

Hypothalamic cholinergic system plays an important role in the regulation of body temperature and fluid balance. We have previously shown that cholinergic stimulation of the anterior hypothalamus and preoptic area was accompanied by a fall in body temperature, increased water intake, and increased Fos protein in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In the present study, to estimate the role played by cholinergic input to the PVN and SON in thermoregulation and water intake, we used microdialysis for cholinergic stimulation with neostigmine and analysis of the nucleus, and also investigated immunoreactivity for c-Fos protein in the brain. This stimulation increased extracellular concentration of acetylcholine in these nuclei. Stimulation of the PVN decreased body temperature and increased water intake. On the other hand, stimulation of the SON increased body temperature. Both in PVN-stimulated and SON-stimulated rats, c-Fos-like immunoreactivity (Fos-IR) was evident in the PVN, SON and certain regions including locus coeruleus (LC), area postrema and nucleus of the solitary tract (NTS). Addition of atropine to the dialysis medium attenuated the increase of Fos-IR and suppressed the cholinergic stimulation-induced responses in body temperature and water intake. These results suggest that cholinergic muscarinic mechanisms in PVN and SON play an opposite function in the regulation of body temperature. The same neuronal pathway including LC and NTS may participate in an advance both in hypothermia and in hyperthermia.

Risk factors for the development of bladder transitional cell carcinoma following surgery for transitional cell carcinoma of the upper urinary tract.

To determine the risk factors for development of transitional cell carcinoma (TCC) of the bladder (BTCC) following surgery for TCC of the upper urinary tract (UUT-TCC) in patients without history of BTCC, 85 patients surgically treated for UUT-TCC (34 female, 51 male; median age 66, range 42-85 years) were reviewed retrospectively. The Cox proportional hazards model was used to assess the association of relevant clinicopathologic factors with BTCC-free survival in patients without a history of BTCC and TCC-specific survival in all. Median follow-up duration was 35 (range 1-193) months. Six patients (7%) had previous histories of BTCC, and 6 others (7%) had concurrent BTCC at the time of surgery for UUT-TCC. Of 70 patients who had no history of BTCC and underwent follow-up cystoscopy, 24 (34%) developed BTCC during follow-up after surgery. Univariate analysis identified female sex, postoperative systemic chemotherapy, and incomplete distal ureterectomy as significant risk factors for new development of BTCC. After multivariate analysis adjusted for age and pathological (p) T stage in the TNM classification, all three factors remained significant, with respective hazard ratios of 5.56 (95% confidence interval (CI), 1.99-15.6; p = 0.001), 3.19 (95% CI, 1.34-7.62; p = 0.009) and 2.99 (95% CI, 1.08-8.26; p = 0.03). Only pT stage was a significant independent risk factor for TCC-specific death. Female sex and postoperative systemic chemotherapy, as well as incomplete distal ureterectomy, are possible riks factors for development of BTCC following surgery for UUT-TCC.

Diagnostic potential of short echo time MR spectroscopy of gliomas with single-voxel and point-resolved spatially localised proton spectroscopy of brain.

Accurate neuroimaging grading of gliomas is useful for management, but techniques such as MRI and CT are not sufficiently reliable. Necrosis is a consistent, decisive prognostic factor and the key diagnostic criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows noninvasive measurement of metabolites in brain tumours and mobile lipids reflect necrosis. However, short echo-time (TE) spectroscopy has been required for reliable assessment of lipids, since their relaxation times are very short. Recent advances have made it possible to perform short-TE MRS. We attempted to evaluate the significance of short TE spectroscopy as part of routine imaging for diagnosis and grading of gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II six; grade III three; grade IV, 16) and in 19 areas of healthy white matter using proton brain examination/single voxel (PROBE/SV) and point-resolved spatially localised spectroscopy (PRESS). With short-TE spectroscopy, lipid signals were detected in all 16 tumours of grade IV, one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms MRS, carried out in 20 of these cases, showed lipid signals in only four of 14 grade IV tumours and in none of the other six. N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in healthy tissues and less than 1.0 in all but one of the gliomas. The mean creatine (Cr)/Cho ratio in each tumour grade was significantly lower than in the healthy tissues. The mean Cr/Cho ratio was also significantly lower in grade IV than in grade II tumours (P < .0005). Considerable overlap in Cr/Cho ratio was observed between grade II and grades III and IV gliomas at long but less so at short-TE MRS. We conclude that short-TE MRS with PROBE/SV and PRESS is of value in grading gliomas.

Changes in presynaptic proteins, SNAP-25 and synaptophysin, in the hippocampal CA1 area in ischemic gerbils.

A general consensus exists that the presynaptic terminals in the hippocampal CA1 area are resistant to ischemic stress in spite of the loss of their target cells (CA1 pyramidal neurons). We have verified this by immunostaining and Western immunoblotting using the antibodies for presynaptic proteins, synaptosomal-associated protein of 25 kDa (SNAP-25) and synaptophysin in gerbils after bilateral carotid artery ligature. In the immunohistochemical analysis, decreases in SNAP-25 and synaptophysin immunoreactivities in the strata radiatum and oriens, especially around the apical dendrite of CA1 neurons, and disappearance of SNAP-25 immunoreactivity in the alveus were observed on day 2 after ischemia. On days 7 and 14, SNAP-25-positive granular materials were expressed in the CA1 area, and intense synaptophysin immunoreactivity around surviving CA1 neurons was observed. Western immunoblot analysis revealed significant decreases of SNAP-25 and synaptophysin (about 60% of control levels) on day 2, and then increase of their proteins (130--140% of control levels) on day 14. These results indicate that presynaptic degeneration occurs in the hippocampal CA1 area after ischemia, and it precedes the delayed neuronal death of CA1 neurons. The presynaptic terminal damage may be responsible for some pathological changes in ischemic brains.

Effects of an oriental herbal medicine, "Saiboku-to", and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats.

Effects of a traditional oriental herbal medicine, "Saiboku-to" and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats were investigated. Saiboku-to inhibited Compound 48/80-induced degranulation of and histamine release from the mast cells, suggesting that Saiboku-to not only possesses anti-histamine release effect from mast cells, but also contains active herbs with this effect. Significant inhibitions were found in 4 of 10 constituent herbs of Saiboku-to: Magnoliae Cortex, Perillae Herba, Bupleuri Radix and Hoelen. In the dose-response curves of the four herbs, the logarithmic linearity was observed for each herb, and 50% inhibitory concentration, the IC50 values, were calculated to be 56.8 microg/ml for Magnoliae Cortex, 175.8 microl/ml for Perillae Herba, 356.6 microg/ml for Bupleuri Radix, and 595.8 microg/ml for Hoelen. One mg/ml of Saiboku-to showing 75% inhibition of Compound 48/80-induced histamine release level from mast cells contains 88.5 microg of Magnoliae Cortex (it was estimated from the dose-response curve that this dose inhibits 62.68% of the Compound 48/80-induced histamine release level), 58.8 microg of Perillae Herba (21% inhibition), 205.9 microg of Bupleuri Radix (35.24% inhibition), and 147.1 microg of Hoelen (11.15% inhibition). From these results, it is suggested that the anti-histamine release effect of Saiboku-to, which contains 10 herbs, may be due mainly to the effect of Magnoliae Cortex and the synergism of the 3 other herbs.

Deep vein thrombosis during chemotherapy in a patient with advanced testicular cancer: successful percutaneous thrombectomy under temporary placement of retrievable inferior vena cava filter.

A 27-year-old man with advanced testicular cancer experienced two events of deep vein thrombosis (DVT) during three cycles of cisplatin-based combination chemotherapy; the first thrombotic event occurred in the inferior vena cava (IVC) following the initial two cycles of chemotherapy and the second thrombotic event occurred in the right iliac vein following the third cycle. For both thrombotic events, he was successfully managed with thrombolytic therapy and percutaneous thrombectomy using a transcatheter hydraulic thrombectomy device under temporary placement of a retrievable IVC filter. Stasis of the IVC due to compression by a retroperitoneal lymphadenopathy of 7 cm in diameter, which was demonstrated on computed tomographic scans at presentation, was considered a major cause of DVT during chemotherapy. Patients with bulky retroperitoneal disease causing stasis of major veins are at high risk of DVT associated with chemotherapy and thromboprophylaxis should be strongly considered during their chemotherapy.

Role of preoptic and anterior hypothalamic cholinergic input on water intake and body temperature.

To elucidate the role played by cholinergic mechanism in the preoptic area (POA) and anterior hypothalamus (AH) in the control of body temperature and water intake of rats, we used microdialysis without disturbing the behavior of unanesthetized animals. After microdialysis, we also investigated immunoreactivity for c-Fos protein in the hypothalamus. Stimulation with neostigmine, an acetylcholine esterase inhibitor, through microdialysis probe increased extracellular concentration of acetylcholine (ACh) in the POA and AH, and was accompanied by a dose-dependent fall in body temperature and increased water intake. Addition of atropine, a muscarinic receptor antagonist, to the dialysis medium containing neostigmine suppressed the neostigmine-induced changes in rectal temperature and water intake. Neostignime markedly increased c-Fos-like immunoreactivity (Fos-IR) in certain hypothalamic areas, including the paraventricular nucleus, supraoptic nucleus and median preoptic nucleus. This increase was also attenuated by atropine. These results suggest that cholinergic inputs and activation of muscarinic processes in POA and AH induced a decline in body temperature and increased water intake.

Hypothalamic cholinergic regulation of body temperature and water intake in rats.

Without disturbing the behavior of unanesthetized rats, the perfusion of neostigmine through microdialysis probe into the anterior hypothalamus (AH), paraventricular nucleus (PVN) and lateral ventricle (LV) decreased body temperature and increased water intake. On the other hand, the perfusion into the supraoptic nucleus (SON) increased the body temperature. The perfusion of neostigmine increased the extracellular concentration of acetylcholine in the perfusion sites except LV. Changes, both decrease and increase, in body temperature and increase in water intake were correlated with increases in c-fos-like immunoreactivity (Fos-IR) in the hypothalamus, pons and medulla. Distinct Fos-IR was found in the PVN, SON, median preoptic nucleus (MnPO), locus coeruleus (LC), area postrema and nucleus of the solitary tract (NTS). Co-administration of atropine with neostigmine completely suppressed the changes in the body temperature, water intake and Fos-IR, all of which were induced by the neostigmine perfusion into AH, PVN and SON. In the LV-perfused rats, on the other hand, co-administration of atropine and neostigmine only partially prevented body temperature reduction and still induced significant hypothermia. These results suggest that muscarinic receptor activation in specific regions of the hypothalamus and the activation of LC and NTS are implicated in the regulation of body temperature and water intake. Other receptor processes are involved in the LV-induced changes.

Local thrombolysis for acute ischemic stroke based on findings of diffusion and perfusion MRI.

SUMMARY: Cerebral per fusion and cerebral tissue integrity were studied in 13 patients with acute embolic stroke in the territory of the internal carotid artery by diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) within six hours after onset. PWI/DWI mismatch lesion was depicted in six patients. MCA was occluded in five of six patients, who underwent local thrombolytic therapy. In three cases, complete restoration of the cerebral circulation was obtained and enlargement of irreversible brain damage compared to initial DWI lesion was prevented. Seven patients without PWI/DWI mismatch did not undergo thrombolytic therapy. Spontaneous reopening of occluded MCA was verified with subsequent cerebral angiography in one of seven patients. CT depicted symptomatic intracerebral hemorrhage in this patient. It is concluded that DWI and PWI in combination are useful in selection of patients for thrombolytic therapy.

A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells.

Leukocyte chemoattractants are involved in the inflammatory response act via G protein-coupled receptors. We report the cloning of a novel human gene encoding the putative orphan receptor, C5L2, belonging to a subfamily of C3a, C5a and formyl Met-Leu-Ph receptors that are related to the chemokine receptor family. C5L2 transcript levels were abundant in granulocytes and immature dendritic cells but not in mature dendritic cells. We speculate that this receptor may regulate the activation of immature dendritic cells and play a role in the chemoattraction of leukocytes to inflammatory regions.

Learning and memory in mice treated with choline oxidase, a hydrolytic enzyme for choline.

Learning and maintenance of memory in mice intraperitoneally (IP) injected with choline oxidase (ChO, 6 units/g), a hydrolytic enzyme for choline (Ch), were assessed by means of a step-through passive-avoidance task. The ChO treatment induced a hydrolysis of free Ch in plasma, which in turn, induced a decrease in cerebral acetylcholine (ACh) release. In the learning test, the ChO-treated mice showed significant inhibition to learn the avoidance from electric shock. In the retention test, the impairment of the memory once established was not produced by posttreated ChO. We concluded that the decreased cerebral cholinergic neurotransmission induced by ChO retarded acquisition of passive-avoidance learning more readily than the maintenance of memory.