Reexamination of vertical activity in rats treated with lithium chloride

Summary Injection of hypertonic LiCl i.p. has several nonspecific adverse effects in rats. No evidence was obtained forJohnson's hypothesis that the effect of LiCl on rearing is mediated by environmental stimuli.Acknowledgments. The author thanks Aarhus University, The Danish Medical Research Council, andMarianne Jensen for assistance.     

The influence of lithium on serum ceruloplasmin

Summary Serum ceruloplasmin oxidase activity did not change in mice treated orally for 120 days with Li₂CO₃ (0.58 mEq/kg/day). After a single i.p. injection of LiCl (20 mEq/kg), a significant activation of ceruloplasmin was observed.R. R. A. is working with a research grant from the Conselho Nacional de Pesquisas (National Research Council of Brasil).     

Control of the hypothalamus-pituitary-adrenal axis in young and older rats injected with thyroxine1–3

Summary Administration of T₄ on alternate weeks for 30 weeks at a dosage which does not alter body weight depresses basal serum corticosterone levels in older rats (575 days), but not in young animals (260 days). Similar serum corticosterone response to HPA axis stimulation occurs regardless of age or T₄ injection.Presented in part at the 8th Annual National Meeting of the American Aging Association, October 1978, San Francisco.Supported by an FRC grant, Graduate College, Bowling Green State University.Acknowledgment is made of the technical assistance of L. Carter, P. Froelich, R. Froelich, J. Ku, M. Meserve and D. Schulte.     

L'action du chlorure de lithium et du sulfocyanure de sodium sur la viscosité de la nucléohistone et des extraits d'embryons d'Amphibiens

Summary (1) LiCl increases the viscosity and decreases the rigidity of nucleohistone; NaSCN has opposite effects.(2) The effects of LiCl and NaSCN on the viscosity of amphibian embryo extracts, as observed byRanzi and his coworkers, seem to be due to the action of these salts on nucleohistone.     

Visual input to rat pineal

Summary Electrophysiological recordings from freely behaving rats, previously implanted stereotaxically with permanent electrodes in the pineal, ventromedial hypothalamus, caudate nucleus, lateral geniculate body and medial geniculate body were obtained. The pineal photic responses revealed 5 sequential components. Injection of a neuronal blocker at the level of the superior cervical ganglion did not alter the earlier photic responses, but did eliminate the late components (N₂–P₃) for 60–90 min after the injection. All of the other responses were unchanged during the experiment. The present experiments demonstrated that photic input travels to the pineal through two pathways.The author is grateful to Dr C.M. Prashad and Ms. Marjorie Brown for technical assistance. Supported in part by grant NS 16596.     

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.     

Biochemical studies on peptide alkaloids: Induction of ion selective mitochondrial swelling

Summary The effect of frangulanine, a cyclopeptide alkaloid isolated fromHovenia dulcis Thunb., on mitochondrial swelling was studied. Frangulanine induced mitochondrial swelling in 0.15 M KCl solution at the concentration of 6.5 M. The alkaloid showed ion selectivity on the induction of mitochondrial swelling. Upon addition of frangulanine, mitochondria underwent swelling in 0.15 M KCl or RbCl solution but in neither NaCl nor LiCl solution.     

Lithium effects upon components of activity in rats.

When lithium chloride was administered to rats several changes occurred in a number of components of activity, some of which were sex-related. There was a reduction in both ambulatory and rearing activity and in behaviour associated particularly with the mouth and nose. The findings are related to a suggestion that lithium effects on behaviour may be more subtle than hitherto thought.     

Lithium effects upon components of activity in rats

Summary When lithium chloride was administered to rats several changes occurred in a number of components of activity, some of which were sex-related. There was a reduction in both ambulatory and rearing activity and in behaviour associated particularly with the mouth and nose. The findings are related to a suggestion that lithium effects on behaviour may be more subtherthan hitherto thought.     

Diabetes alters drug metabolism-in vivo studies in a streptozotozin-diabetic rat model

Summary The influence of experimental streptozotozin-induced diabetes on hepatic drug metabolism in vivo has been studied in rats, using¹⁴CO₂-exhalation after¹⁴C-aminopyrine injection. Male diabetic rats showed a decreased (–18%), females an increased (+19%)¹⁴CO₂-exhalation compared to controls, indicating altered hepatic drug metabolism due to diabetes.     

Hepatic and cerebral coenzyme a contents after intravenous injection of coenzyme a in rats

Summary Hepatic CoA concentrations and contents were significantly higher in rats having received i.v. CoA injections than in control rats. Maximum hepatic CoA concentrations were found 0.5–1 h after injection. In rat brain, no increase in CoA concentration was detected after i. v. injection of CoA.Acknowledgments. We thank MissV. Godly and MissA. M. Reber for excellent technical assistance. This work was supported by grants from F. Hoffmann-La Roche & Co., AG, Basel.     

Involvement of H1 receptors in the central antinociceptive effect of histamine: Pharmacological dissection by electrophysiological analysis

Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025–0.1 M/rat) to arthritic rats induces a dose-related inhibition of the neuronal thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s) of HA receptors involved in this depressing activity of the amine we used electrophysiological techniques to examine the effects of i.c.v. administration of H₁ and H₂ agonists and antagonists on the spontaneous and evoked nociceptive firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant. The H₁ agonist 2-pyridylethylamine (0.4–1.0 M/rat, i.c.v) displayed a dose-dependent antinociceptive effect very similar to that of HA, while the H₂ agonist dimaprit (0.05–0.2 M/rat, i.c.v.) did not modify thalamic firing. Neither mepyramine (H₁ antagonist, 0.1 M/rat, i.c.v.) nor zolantidine (H₂ antagonist, 0.01 M/rat, i.c.v.) modified the evoked firing of rat thalamic neurons. When administered before HA (0.1 M/rat, i.c.v.) mepyramine but not zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of the present electrophysiological results, we suggest that a specific interaction of histamine with H₁ receptors may be important for its antinociceptive effect on afferent peripheral inputs to the thalamus.     

Renal vascular reactivity to ATP in hyper- and hypothyroid rats

The effects of adenosine triphosphate (ATP) on the renal vasculature of isolated kidneys from control, hyper- and hypothyroid rats were characterized. ATP responsiveness was evaluated in basal tone and in raised tone (phenylephrine 10^–6 M) preparations. These responses were compared with those obtained with barium chloride or sodium nitroprusside (SNP), used respectively as nonreceptor agonists for vasoconstriction or vasodilation. In preparations at basal tone, ATP produced dose-related vasoconstriction, which was increased in hyperthyroid kidneys, and was severely attenuated in kidneys from hypothyroid rats. In raised tone preparations from control rats ATP produced a dual response: vasoconstriction at low doses, which declined with increasing doses to give way to vasodilator responses; biphasic responses were found in some kidneys. Hyperthroid kidneys showed increased pressor responses and a vasodilator response similar to those seen in kidneys from control rats. However, in hypothyroid kidneys the vasodilator response was abolished. The responses to barium chloride and to SNP were significantly increased and decreased in hyper- and hypothyroid kidneys, respectively; vasoconstrictor responses to SNP were also found in hypothyroid kidneys. Hence the abnormal responses to ATP observed in both thyroid dysfunctions may be partially explained by unspecific alterations in the contractile machinery of the renal vasculature in these kidneys. However, ATP responsiveness (vasoconstriction at low tone and vasodilation at raised tone) was more severely affected in hypothyroid kidneys, suggesting that purinergic (P_2X and P_2Y) receptor activity may be decreased in these organs.     

Localisation ultrastructurale de l'œstradiol et du moxestrol dans les cellules gonadotropes du rat par immunocytologie après cryo-ultramicrotomie: Caractérisation de la spécificité hormonale

Summary Estradiol (E₂) was specifically localized by immunocytochemistry in the cytoplasm and in the nucleus of the gonadotropic cells. The immunocytochemical reaction was not observed after injection of moxestrol, but it was not modified by injection of testosterone, progesterone, or dexamethasone. These data suggest that E₂ might be bound to a high-affinity binding-site which could also have a hormonal specificity.

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Ce travail a bénéficié d'une aide de l'I.N.S.E.R.M., ATP 58 78 90 contrat 48 (P.M. Dubois).     

Induction of the in vitro p-hydroxylation of14C-amphetamine stereoisomers in phenobarbital-treated rats

Summary The rate of p-hydroxylation of¹⁴C-(-)-amphetamine by liver microsomes was higher than that of (+)-isomer in phenobarbital-treated male rats. The apparent K_m values for (-)- and (+)-amphetamine hydroxylation were 4.54×10^–5 M and 2.27×10^–5 M respectively, in both treated and control animals.     

The influence of lithium on serum ceruloplasmin.

Serum ceruloplasmin oxidase activity did not change in mice treated orally for 120 days with Li2CO3 (0.58 mEq/kg/day). After a single i.p. injection of LiCl (20 mEq/kg), a significant activation of ceruloplasmin was observed.     

The role of the kidney in gastrin metabolism in the rat

Résumé Les taux moyens de sécrétion d'acide gastrique due à l'injection par voie i.v. du SHGI et de gastrine bovine brute ont été sensiblement plus élevées et les périodes de réaction plus longues chez les rats testés que chez les rats de contrôle. Aucune différences significative n'a été observée ni dans le taux moyen de sécrétion acide ni dans la période de réaction chez les deux types de rats, après injection d'histamine dihydrochloride.

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The authors are grateful to M.R.C. London for the SHGI sent to M.O.O. The work has been made possible by a fund from the University of Ibadan Senate Research Grant given to M.O.O.     

Covalent binding of aflatoxin B1 to liver DNA in rats pretreated with ethanol

Summary Male Fischer F-344 rats were given ethanol in the drinking water and/or by single oral administration. Following this, the animals received p.o. 100 ng/kg of the hepatocarcinogen [³H]aflatoxin B₁ (AFB₁). 24 h later, the level of DNA-bound AFB₁ was determined in the liver and was found not to be affected by any type of ethanol pretreatment. A cocarcinogenic effect of ethanol in the liver is therefore unlikely to be due to an effect on the metabolic activation and inactivation processes governing the formation of DNA-binding AFB₁ metabolites.To whom correspondence should be addressed.Acknowledgment. We thank the European Science Foundation for the Toxicology Research Fellowship awarded to M.M.     

Evidence for suppression of immune function by insulin-like growth factor-1 in dwarf rats in vivo

These studies were undertaken to investigate the effects of increasing or decreasing IGF-1 levels on aspects of immune function in rats. Female dwarf rats were treated with recombinant human IGF-1 or with a potent sheep anti-IGF-serum. Body weight, thymus weight and spleen weight increased with IGF-1 treatment (p<0.001), while there was no effect of anti-IGF-1 treatment when compared with the appropriate normal sheep serum (NSS) treated controls. IGF-1 treatment significantly decreased WBC and RBC counts, but increased the ratio of CD4⁺:CD8⁺ T-cells. Anti-IGF-1 serum had no effect on these parameters compared with NSS. However anti-IGF-1 was associated with increased T-cell numbers, decreased natural killer cells, and enhancement of the animals' ability to produce specific IgG in response to injection of keyhole limpet haemocyanin (KLH). These results indicate that IGF-1 may suppress immune function although increasing the size of immune organs such as spleen.These studies were part of an M.Sc. at the University of Waikato, Hamilton, New Zealand.     

Increased Na+-H+ exchanger activity in the ileal brush-border membrane of spontaneously hypertensive rats

In the present study, we have examined the intestinal Na⁺ transport, through the Na⁺-H⁺ exchanger, in ileal brush-border membrane vesicles (BBMV) isolated from spontaneously hypertensive rats (SHR), and normotensive Wistar Kyoto (WKY) rats as a control group. Na⁺ uptake into ileal BBMV was stimulated in the presence of a proton gradient (pH 5.5 inside/pH 7.5 outside) in SHR and WKY rats, resulting in a transient accumulation (overshoot) in both groups of rats. No overshoot was observed in the absence of a pH gradient. The magnitude of the accumulation was significantly higher in SHR than in WKY rats. Uptake of Na⁺ at equilibrium was identical in the presence and the absence of a proton gradient and was not changed in SHR. The use of amiloride inhibited pH gradient-driven Na⁺ uptake in a dose-dependent manner with a Ki of 90 μM and 100 μM for SHR and WKY rats, respectively. The relationship between proton gradient-driven Na⁺ uptake and external Na⁺ concentration was saturable and conformed to Michaelis-Menten kinetics in both SHR and WKY rats. Lineweaver-Burk analysis of the pH gradient-driven Na⁺ uptake indicated values of V_max that were significantly increased in SHR compared to WKY rats (11.4±0.55 nmol/mg/8 s vs. 4.96±0.78 nmol/mg/8 s for SHR and WKY rats, respectively). In contrast, similar K_m values for Na⁺ were found between SHR and WKY rats (4.0±0.2 mM vs. 4.9±0.6 mM for SHR and WKY rats, respectively). These studies show derangement in ileal BBMV Na⁺ transport of SHR, which is characterized by increased Na⁺-H⁺ exchanger activity. Received 18 December 1996; received after revision 3 February 1997; accepted 7 February 1997