Context-Dependent Passive Avoidance Learning in the Terrestrial Slug Limax.

The terrestrial slug Limax has been used as a model animal for studying the neural mechanisms underlying associative olfactory learning. The slug also innately exhibits negative phototactic behavior using its eyes. In the present study, we developed an experimental paradigm for quantification of slug's negative phototaxis behavior, and investigated whether the nature of the negative phototaxis can be modified by learning experience. The experimental set-up consists of light and dark compartments, between which the slug can move freely. During conditioning, the slug was placed in the light compartment, and an aversive stimulus (quinidine sulfate solution) was applied when it reached the dark compartment. After a single conditioning session, the time to reach the dark compartment significantly increased when it was tested following 24 hr or one week. Protein synthesis inhibition immediately following the conditioning impaired the memory retention at one week but not at 24 hr. The retrieval of the memory was context-dependent, as the time to reach the dark compartment did not significantly increase if the slug was placed on a floor with a different texture in the memory retention test. If the aversive stimulus was applied when the slug was in the light compartment, the time to reach the dark compartment did not increase after 24 hr. This is the first report demonstrating the capability of the slug to form context-dependent passive avoidance memory that can be established in a single conditioning session.

Risk factors for ganciclovir-induced thrombocytopenia and leukopenia.

Ganciclovir is a nucleoside guanosine analogue that exhibits therapeutic activity against human cytomegalovirus infection, and is primarily excreted via glomerular filtration and active tubular secretion. The adverse effects induced by ganciclovir therapy are generally of a hematological nature and include thrombocytopenia and leukopenia. Low marrow cellularity and elevated serum creatinine have been identified as risk factors for ganciclovir-induced neutropenia. However, the risk factors for thrombocytopenia have yet to be determined. Therefore, this study investigated patients administered ganciclovir to determine the risk factors for thrombocytopenia and leukopenia. Thrombocytopenia occurred in 41 of these patients (30.6%). Multivariate logistic regression analysis identified three independent risk factors for thrombocytopenia: cancer chemotherapy (odds ratio (OR)=3.1), creatinine clearance (<20 mL/min) (OR=12.8), and the ganciclovir dose (≥12 mg/kg/d) (OR=15.1). Leukopenia occurred in 36 patients (28.6%), and white blood cell count (<6000 cells/mm(3)) (OR=3.7) and the ganciclovir dose (≥12 mg/kg/d) (OR=7.8) were identified as risk factors. These results demonstrated that several factors influenced the occurrence of ganciclovir-induced thrombocytopenia and leukopenia, and suggest that special attention should be paid to patients receiving cancer chemotherapy with a low creatinine clearance (<20 mL/min) and high dose (≥12 mg/kg/d) in order to avoid ganciclovir-induced thrombocytopenia.

Cyclosporine A-increased nitric oxide production in the rat dorsal hippocampus mediates convulsions.

To test whether nitric oxide (NO) participates in cyclosporine A (CsA)-induced neurotoxicity including convulsions, we examined the effect of an NO synthase inhibitor on convulsions induced by combined treatment with CsA and bicuculline in mice and the effect of CsA on NO production in the dorsal hippocampus using an in vivo microdialysis method in rats. CsA (200 mg/kg, i.p.) significantly increased the intensity of convulsions induced by an intracerebroventricular injection of bicuculline (25 pmol) in mice. This facilitation was blocked by N omega -nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, but not by N omega -nitro-D-arginine methyl ester (D-NAME), an inactive form of L-NAME (10 mg/kg, i.p.). CsA (20-50 mg/kg, i.p.) dose-dependently increased NO 2 - levels in dialysates obtained with microdialysis in the rat dorsal hippocampus. This enhanced NO 2 - formation was blocked by L-NAME but not by D-NAME (50 mg/kg, i.p.). These findings suggest that CsA stimulates NO production and induces convulsions as a result of an interaction between NO and the gamma-aminobutyric acid (GABA) system in the hippocampus.

In vivo evidence for a lack of central effect of ebastine, an antihistaminic agent, in rats: a microdialysis study.

The effects of ebastine and its active metabolite carebastine on brain dopamine uptake and the accessibility to brain were compared with those for a classical antihistaminic agent chlorpheniramine by using the microdialysis technique. Both carebastine and chlorpheniramine potently inhibited brain [(3)H]dopamine uptake and increased the extracellular concentration of dopamine in the striatum after local perfusion via microdialysis probes, although systemic injection of ebastine but not chlorpheniramine did not change the dopamine level. These findings suggest that neither ebastine nor carebastine affects central dopamine metabolism because of a limited access to brain, in spite of having a potent inhibitory action on neuronal dopamine uptake.