Participation of ACTH1–10 and ACTH4–10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH_1–10 and ACTH_4–10 on [³H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the B_max (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing K_D (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased B_max, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, K_D values were unchanged. The i.c.v injection of ACTH_1–10 to hypophysectomized animals significantly increased B_max, an effect that was enhanced by simultaneous i.c.v. injection of ACTH_1–10+melatonin, reaching higher values of B_max than the i.c.v. injection of these hormones individually. No significant changes in K_D values were found after ACTH_1–10 and/or melatonin administration. However, the i.c.v. injection of ACTH_4–10 to hypophysectomized rats did not change B_max, although it significantly increased K_D values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH_4–10, returning K_D to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify B_max of BNZ binding in the ACTH_4–10-injected group, the higher dose, 20 ng, significantly increased B_max. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.     

The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats

Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12h with the fourth dose given 0.5 h before experiments, dose-dependently lessened gastric glandular mucosal ulceration produced by cold-restraint stress for 2h. When given intracerebrally (i.c.) (0.1, 0.5 or 1g), using the same treatment regimen, infusion of ondansetron 1 g into the nucleus amygdaloideus centralis decreased stress-evoked ulcers; in contrast, injection of the same dose into the nucleus accumbens intensified these lesions. The associated stress-induced stomach wall mast cell degranulation was unaffected by all s.c. or i.c. doses of ondansetron. Pretreatment with disodium cromoglycate i.p. alone, or concurrently with ondansetron s.c., prevented not only ulceration but also mast cell degranulation. 5-Hydroxytryptamine₃ receptor antagonism appears to inhibit stress-evoked ulcers mainly by blocking the peripheral effects of the amine after its release from the gastric mucosal mast cells.     

Elimination and metabolism of dimethylnitrosamine (DMN) byXenopus laevis and other amphibians

Summary The elimination of (¹⁴C)-DMN after i.p. injection intoXenopus was measured, as was the metabolism in vitro of (¹⁴C)-DMN by liver fromXenopus and 9 other amphibian species. In view of its rapid elimination from the body and low rate of metabolism byXenopus liver in vitro, DMN is unlikely to be toxic or carcinogenic inXenopus.This work was supported by a grant from the Cancer Research Campaign. We are also grateful to Dr P. F. Swann, both for the supply of DMN and DEN and for many useful discussions.     

Antagonism by haloperidol of the suppression of exploratory locomotor activity induced by the local application of(−)3-(3-hydroxyphenyl)-N-n-propylpiperidine into the nucleus accumbens of the rat

Summary The injection of (–)3-PPP into the nucleus accumbens, 10 g/side, produced a suppression of exploratory locomotor activity without affecting treadmill locomotion. Furthermore, the suppression of exploratory locomotor activity produced by (–)3-PPP was antagonized by the administration of haloperidol, 25–50 g/kg i.p.Acknowledgments. The figures were prepared by M. Kröning at the Department of Psychology, University of Göteborg. This work was supported by Torsten and Ragnar Söderberg's Foundation, Magn. Bergvall Foundation and Åke Wiberg Foundation.     

Reappearance in vivo of neuraminidase-sensitive sialic acid in L 5222 rat leukemia cells

Summary Cell electrophoretic data and quantitative sialic acid determination show that, 16 to 20h after i.p. implantation of neuraminidase-treated L 5222 rat leukemia cells, the original sialic acid content at the cell periphery is reconstituted.This investigation was performed within the EORTIC Cell Surface Project Group and supported by the Swiss National Science Foundation, Grant No. 3.901.72, and by the Zürich Cancer League.     

The distribution of carcinogens, 4-nitroquinoline-1-oxide and 4-hydroxyaminoquinoline-1-oxide,in the nervous system and its possible neurotoxicological significance

Summary 4-NQO-¹⁴C can enter the grey matter parenchyma of the central nervous system of mice after i.v. injection. The level of its uptake by the central grey is higher than that taken up by the central white and by the trigeminal and spinal dorsal root ganglia. This pattern of distribution is strikingly different from that obtained after i.v. injection of 4-HAQO-¹⁴C, suggesting the possible occurrence of 4-NQO encephalomyelopathy having entirely different sites of lesions from those of 4-HAQO neuropathy.This work was supported by a grant-in-Aid for Special Project Research from the Ministry of Education, Science and Culture of the Japanese Government (No. 321304, 1978).     

Induction of microsomal drug-metabolizing enzymes caused by hexobarbital

Summary Hexobarbital was given to anaesthetized mice for a period of 7 h by repeated i. p. injection, first of 100 mg/ kg, then several times of 50 mg/kg. A high level of hexobarbital was maintained in the liver. The activity of microsomal drug-metabolizing enzymes was induced by this treatment with hexobarbital. 30 min after a single i. p. injection of 100 mg/kg of hexobarbital, there was a significant inhibition of aminopyrine N-demethylase but none of cytochrome c and neotetrazolium reductases.—Hexobarbital in vitro inhibits aminopyrine N-demethylase but not cytochrome c reductase.     

Incorporation of35S-labelledl -cysteine andl -methionine in the ependyma of the subcommissural organ in the thyroidectomized rat

Zusammenfassung Nach Thyreoidektomie wurde die Inkorporation von i.p. verabfolgtem und mit³⁵S markiertem Cystein und Methionin im Ependym des Subkommissuralorgans der Ratte untersucht. Die Cystein-Aufnahme war stärker reduziert als diejenige von Methionin.

---

---

This study was financially supported by the National Research Council for Medical Sciences, Finland and the Sigrid Jusélius Foundation, Helsinki (Finland).     

A method for the incorporation of radioactive isotopes in the sea urchin egg

Riassunto Con la iniezione di 10–20µc di Metionina-S³⁵ nella cavità celomatica di femmine adulte diParacentrotus lividus si ottiene una rapida ed efficiente incorporazione dell'isotopo nelle uova. Si discutono i vantaggi del metodo rispetto a quello attualmente in uso.

---

---

Aided by a Grant from the Rockefeller Foundation, on leave from the Nagoya University, Japan.     

Characteristic high label of stomach mast cells after subcutaneous injection of 5-hydroxytryptamine in mice

Zusammenfassung Nach s.c. und i.p. Injektion von C¹⁴-5-Hydroxytryptamin an Mäusen wurde die Radioaktivität verschiedener Organe autoradiographisch untersucht. Eine charakteristische starke Radioaktivität, welche bis zu 6 h anhielt und nach 24 h verschwand, wurde bei s.c. Injektion schon nach 15 min in den Gewebsmastzellen der Magenwand festgestellt. Mastzellen anderer Organe zeigten nur schwache Radioaktivität. Bei i.p. Injektion tritt eine verzögerte Speicherung der radioaktiven Substanz in den Magenmastzellen auf. Die charakteristische Affinität von Serotonin zu den Magenmastzellen dürfte die Ursache des experimentellen Magengeschwürs nach Serotoninbehandlung sein.     

Irradiation of the head by60Co opens the blood-brain barrier for drugs in rats

Summary The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a⁶⁰Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of³H₂O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.     

The effects of intracerebrally administered RNA,tubercidin and histones on learning in rats

Zusammenfassung RNA aus Hefe, RNA-Hydrolysat, Tubercidin und mit Lysin angereichertes Histon, i.c. oder i.p. injiziert, hatten keine Wirkung auf die Lernfähigkeit von Ratten. Intracerebral injiziertes¹⁴C-RNA verbreitete sich schnell über das ganze Gehirn und verschwand relativ schnell wieder. Nach i.p. Injection von¹⁴C-RNA konnte jedoch ein geringer Betrag von¹⁴C im cerebralen RNA gefunden werden.     

Effects of selective dopamine D1 and D2 antagonists on male rat sexual behavior

Summary The effects of selective dopamine (DA) D₁ and D₂ antagonists on male rat sexual behavior were investigated. The D₁ antagonist (+)SCH-23390, 25–100 g kg^–1 s.c. –20 min, and the D₂ antagonist raclopride, 0.1–1.6 mg kg^–1 s.c., –20 min, decreased both the number of mounts and intromissions preceding ejaculation. No statistically significant effects in the time up to ejaculation or in the time up to the first intromission were noted, whereas both compounds produced a statistically significant increase in the post-ejaculatory interval. The effect can generally be characterized as psychomotor inhibition, and no evidence was obtained for a specific role of DA D₁ or D₂ receptors in the mediation of male rat sexual behavior.The expert technical assistance of Ms Elisabeth Wallin is gratefully acknowledged. The figures were skilfully prepared by Ms Madelene Kröning at the Department of Psychology. This study received support from the Bank of Sweden tercentenary Foundation, The Swedish MRC and Wilhelm and Martina Lundgren Foundation.     

Induction of microsomal drug-metabolizing enzymes caused by hexobarbital.

Hexobarbital was given to anaesthetized mice for a period of 7 h by repeated i. p. injection, first of 100 mg/kg,then several times of 50 mg/kg. A high level of hexobarbital was maintained in the liver. The activity of microsomal drug-metabolizing enzymes was induced by this treatment with hexobarbital. 30 min after a single i. p. injection of 100 mg/kg of hexobarbital, there was a significant inhibition of aminopyrine N-demethylase but none of cytochrome c and neotetrazolium reductases. Hexobarbital in vitro inhibits aminopyrine N-demethylase but not cytochrome c reductase.     

Mesothelzellveränderungen nach der intraperitonealen Injektion von denaturiertem Phytohaemagglutinin

Summary After the i.p. injection of heat denatured PHA, mesothelial cell changes are similar to those found after the application of natural PHA. While vacuolization of mesothelial cells and signet ring cell formation is strongly marked after the injection of natural PHA, this reaction is minor if denatured PHA is used. Furthermore, the peritoneal fluid does not contain hyaluronic acid in detectable amounts.

---

---

Die Untersuchungen wurden mit finanzieller Unterstützung durch die Deutsche Forschungsgemeinschaft durchgeführt.     

Versuche zur chemischen GedächtnisÜbertragung von farbdressierten Goldfischen auf undressierte Tiere

Summary 36–48 h after the i.p. injection of a low molecular brain extract prepared from colour-trained goldfishes into naive goldfish, these recipients show positive reactions comparable to those shown by the donors. 12–24 h after the injection, the recipients showed an increased activity. No changes in behaviour have been noticed in the recipients of i.p. injections of low molecular brain material from untrained donor fish.     

Is attenuation of tRNA charging responsible for the inhibition of protein labelling accompanying depolarisation of the cerebral cortical cells?

Summary Topical application of concentrated solutions of KCl resulted in reduction of charging of tRNA 7 min after s.c. injection of L-(U-¹⁴C) leucine. Neither radioactivity nor pool size of the total amino acids changed during this period.     

Radiostrontium-Ausscheidung im Kot junger Ratten nach calciumreicher Ernährung

Summary Young immature rats of both sexes were fed with a diet either high (1.95%) or low (0.31%) in Ca content. A s.c. injection of weightless⁹⁰Sr results in a better excretion of radiostrontium with the faeces during feeding with high Ca diet. The retention of activity in the femori 30 days after injection is, in the same case, lower than by feeding with low Ca diet.     

Comparative incorporation of uridine-3H into nucleolar RNA of mouse subcutaneous and skin tissues at early times after 20-methylcholanthrene administration

Summary A single s.c. injection of 20-methylcholanthrene (1 mg in 0.2 ml olive oil) is found to stimulate the relative uptake of uridine-³H by the skin and the s.c. tissue 17- and 3fold respectively, 24 h post-administration.     

Presence of high adenosine triphosphatase activity in lenses and erythrocytes of embryonic and young chicks

Résumé Dans le cristallin et les erythrocytes de poussins à l'état embryonnaire et quelques jours après l'éclosion, l'activité de l'ATPase est beaucoup plus intense que chez d'autres animaux. Ce fait correspond bien à la forte incorporation de Rb⁸⁶ dans leur cristallin.

---

---

This work was supported by grants from the National Health and Medical Research Council of Australia, the Clive and Vera Ramaciotti Foundation and the Helena Rubinstein Foundation. Inc. J. D. G. was supported by a fellowship from ATN Channel 7, Sydney.