The ontogenesis of rearing and stereotypy behavior in response to apomorphine were investigated in the developing rat. The rearing was rarely observed in 15-day-old rats but distinctly in 18-day-old ones. A subcutaneous injection of apomorphine in dose of 1 mg/kg or 2 mg/kg decreased the frequency of rearing in older animals than day 20. On the other hand, 15-day-old rats were already responsive to apomorphine in stereotypy behavior. There was a reciprocal relationship between rearing and stereotypy responses to apomorphine in rat older than 18 days. Functional relationship between rearing and stereotypy in response to apomorphine were discussed in view of the central dopaminergic mechanisms in developing rats.

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The direct action of bisulfite on cultured mammalian cells was studied. Chinese hamster cells precultured in plastic dishes for 2 hr were treated for 1 hr with balanced salt solutions containing bisulfite. Then they were washed, and their colony-forming ability in normal medium was determined. Significant decrease in the colony formation was observed upon treatment with bisulfite solutions over 30 mM concentration. The decrease in the colony number was found to be due to detachment of the cells from the dishes during treatment with bisulfite and subsequent washing. When the preculture time was prolonged to allow the cells to adhere to the dish more firmly, the effect of bisulfite was no longer observable. These results indicate that factors required for cell-substratum adhesion are susceptible to bisulfite.

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Male IVCS mice fed pellets containing 8 nmol methylmercuric chloride (MMC)/g feed for 32 days were additionally inhaled elemental mercury vapor (Hg°) or injected mercuric chloride (Hg²⁺). The modified distribution of accumulated organic mercury was observed 24 hr after exposure to inorganic mercurials. The body burden of organic mercury decreased significantly in MMC+Hg²⁺ treated mice and moderately (not significant) in MMC+Hg°treated mice when compared with MMC treated mice. In spite of the decreased body burden, the organic mercury levels in brain, kidneys and blood of MMC+Hg° treated mice, and in kidneys of MMC+Hg²⁺ treated mice were elevated. In bile, organic mercury concentration after Hg° or Hg²⁺ exposure was reduced. The decrease of the blood cells-to-plasma ratio of organic mercury in mice after Hg° exposure is in agreement with the data reported for workers exposed to mercury vapor.

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Phenthiazamine was developed by Sekizawa et al. as a centrally acting anesthetic for fish. Frog sympathetic ganglion was used as a model to elucidate the mechanism of its anesthetic action. The positive ganglionic potential was enhanced immediately after application ; then, the potential and the late negative ganglionic potential were markedly reduced by an anesthetic concentration of this compound. The hyperpolarization caused by 1 mM dopamine was enhanced by phenthiazamine. This enhancement of dopamine hyperpolarization and of the positive ganglionic potential may coincide with the fact that cyclic adenosine monophosphoric acid (cAMP) phosphodiesterase was inhibited by the compound as shown in our previous paper. Guinea-pig ileum contraction elicited by electrical field stimulation and by dimethyl-phenyl-piperadinium (DMPP) was reduced by a similar concentration of this compound, while the contraction elicited by acetylcholine and methacholine was not inhibited. The inhibition of contraction elicited by electrical field stimulation and DMPP may thus due to inhibition of acetylcholine release by this compound. The inhibition of ileum contraction by this compound was reversed by higher doses of Ca²⁺ (5.5 mM). The time required to reduce the positive ganglionic potential in the sympathetic ganglion by phenthiazamine was prolonged in the presence of higher concentrations of Ca²⁺. The Ca²⁺-dependent action potential of guinea-pig ureter was reduced by this compound, whereas it did not affect the Na⁺-dependent action potential.

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Effects of olfactory bulbectomy, and lesions of the septum and dorsal hippocampus on emotionality as well as on the simple conditioned avoidance response in a two-way shuttle box were investigated in rats. The rats with bilateral olfactory bulbectomy (O.B. rats) showed hyperactivity and aggressive behavior, including mouse-killing behavior (muricide), and those with septal lesions exhibited hyperreactivity and hypoactivity, while the rats with hippocampal lesions became hypoactive without showing hyperreactivity. The O.B. and septal rats, on an average, showed a facilitation in acquisition of the conditioned avoidance response and a retardation in extinction. The muricidal group of O.B. rats, however, showed slower acquisition, while the nonmuricidal O.B. rats showed much faster acquisition and slower extinction than intact rats. Hippocampal lesions retarded acquisition.

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Biologically interesting 6-mercaptopurine 2'-deoxyriboside (3) was synthesized starting from 2'-deoxyadenosine via sulfhydrolysis method in only three steps. Reaction of 2'-deoxyadenosine 1-oxide (1) with methyl iodide followed by alkaline treatment resulted in a rearrangement leading to give 2 in good yield. Sulfhydrolysis of 2 with aqueous pyridinehydrogen sulfide at 45° for 8 days gave 3 in satisfactory yield. Methylation of 3 with methyl iodide afforded 6-methylthiopurine 2'-deoxyriboside (4). Reaction of 4 with hydroxylamine gave 6-hydroxyaminopurine 2'-deoxyriboside (5). Direct replacement of 6-position of 3 with hydrazine hydrate afforded 6-hydrazinopurine 2'-deoxyriboside (6). On the other hand, reaction of 1 with benzyl bromide followed by alkaline treatment afforded 6-benzyloxy-aminopurine 2'-deoxyriboside (7). The antitumor activities of 3 and related compounds against ascites Sarcoma 180 and Nakahara-Fukuoka sarcoma in mice were compared with 9-β-D-arabinofuranosyladenine and its 5'-phosphate, 6-mercaptopurine, and 9-β-D-ribofuranosyl-6-mercaptopurine.

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The mesolimbic-striatal content of 3, 4-dihydroxyphenylacetic acid (DOPAC) gradually increased with age in the developing rat. An intraperitoneal (i.p.) injection of apomorphine (2 mg/kg) or haloperidol (0.1 mg/kg) caused a significant change in the DOPAC content on day 20 and day 70, but not on day 7. However, a higher dose of apomorphine (10 mg/kg, i.p.) or haloperidol (5 mg/kg, i.p.) as well as that of α-flupenthixol (0.5 mg/kg, i.p.) significantly affected the mesolimbic-striatal content of DOPAC in 7-day-old rats. In 24-day-old rats subchronically treated with haloperidol (1 mg/kg to 10 mg/kg for 10 days, s.c.), apomorphine (2 mg/kg, i.p.) produced a significant reduction in the mesolimbic content of DOPAC at the withdrawal stage of the drug, but not in control rats. It is suggested that mesolimbic-striatal dopamine (DA) receptors which are not fully sensitive to DA agonists and antagonists on day 7 reach functional maturity by 20 days of the postnatal age in the rat.

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Autologous immune complex (AIC) nephritis was induced in rats with a single footpad injection of renal tubular epithelial antigen suspended in complete Freund's adjuvant. It was suggested by gel filtration of serum on Sephadex G-200 column that increase in the concentration of macroglobulins was the first alteration reflected on the serum proteins after immunization ; the concentration of macroglobulins increased while the concentrations of albumin and γ-globulin still remained in the normal range. The effect of 6α-methylprednisolone sodium succinate (MP-S), 6α-methylprednisolone (MP) and cyclophosphamide on the AIC nephritis in rats was studied. "Pulse" therapy, that is, an intraperitoneal administration of a large dose (26.5 mg/kg) of MP-S for 3 successive days a week and followed by an intermission for 4 days a week was started from the week of immunization with renal tubular epithelial antigen and continued for 8 weeks, resulting in the retardation of the AIC nephritis induction associated with a partial suppression of the development of proteinuria. Treatment with MP (4 mg/kg) or cyclophosphamide (10 mg/kg) every other day from the week of immunization for 8 weeks partially retarded or completely suppressed the AIC nephritis induction, respectively. On the other hand, the MP-S "Pulse" therapy and the MP treatment of rats suffering from the already established AIC nephritis resulted in no apparent improvement of the disease.

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