Influence of hydrochlorothiazide on the pain threshold and on the antinociceptive activity of morphine, in rats

Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.     

Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo

Summary High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.     

Influence of flupirtine,a novel nonopioid analgesic agent on somatosensory evoked potentials in rats

The effect of flupirtine, a novel nonopioid analgesic, on somatosensory evoked potentials (SEP) was investigated in anesthetized rats. Primary somatosensory potentials were evoked in the cerebral cortex by stimulation of the skin of the whiskery part of the face. Flupirtine injected i.p. dose-dependently prolonged the latency and reduced the amplitude of SEP with ID₅₀-values of 5.4 mg/kg (2.6–9.3 mg/kg) and 7.9 mg/kg (3.9–13.8 mg/kg), respectively. This effect of flupirtine (10 mg/kg, i.p.) on the latency and the amplitude of SEP, did not change when naloxone (1 mg/kg, i.p.) was given before flupirtine. The results indicate that the analgesic flupirtine decreases the primary somatosensory evoked potential by diminishing the excitability of cortical neurons. Opioid mechanisms are not involved.     

Intracerebroventricular injection of cerebrospinal fluid (CSF) from a patient with congenital indifference to pain induces analgesia in rats

Summary CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.     

The effects of acute and chronic morphine on regional distribution of cardiac output in brain

Summary Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.     

Both thermal and nociceptive afferents influence the unit activity of the neurons in the corpus striatum

Summary Both thermal and nociceptive stimulation in the periphery were shown to influence the neuronal activity recorded in the striatal area. Both the thermal and nociceptive sensitivity of the striatal neurons were closely related.The authors are grateful to the Alexander von Humboldt-Stiftung (Bad Godesberg, Bonn, Federal Republic of Germany) for donations of the necessary equipment for the present study. The research reported here was supported by grants from the National Science Council (Taipei, Taiwan, Republic of China)     

Impact of neuropathic pain on the gene expression and activity of cytochrome P450side-chain-cleavage in sensory neural networks

Development of efficient therapy against chronic and stubborn pains requires fundamental identification of adequate cellular and molecular targets. This study combined cellular, molecular and biochemical approaches to investigate the gene expression and enzymatic activity of cytochrome P450side-chain-cleavage (P450scc) in spinal neural networks under normal and neuropathic pain states. P450scc is the key onset enzyme for steroidogenesis in endocrine glands and for neurosteroid biosynthesis in nerve cells. The P450scc gene was over-expressed in spinal and supra-spinal networks during neuropathic pain provoked by sciatic nerve ligature. Plasticity was observed in P450scc cellular distribution in pain circuits and its activity also increased inducing in vivo, hyper-secretion of pregnenolone and allopregnanolone which strongly stimulates type A receptors for g-aminobutyric acid, a pivotal neurotransmitter involved in pain modulation. These results, by establishing a direct link between neuropathic pain and neuroactive steroid formation in the nervous system, open new perspectives for chronic-pain modulation by endogenous neurosteroids.Received 8 June 2004; received after revision 2 July 2004; accepted 13 July 2004     

Hypothalamic tyrosine hydroxylase activity,plasma gonadotropin and prolactin levels after aminooxyacetic acid in ovariectomized rats

Summary Plasma concentrations of gonadotropin, prolactin and hypothalamic tyrosine hydroxylase (TH) activity were measured in ovariectomized rats treated with aminooxyacetic acid (AOAA), a drug which elevates brain GABA levels. Hypothalamic TH activity was significantly increased with a significant decrease in prolactin (Prl) release. Plasma levels of gonadotropins were not modified by AOAA. These results support an inhibitory action of GABA on Prl release possibly mediated through hypothalamic dopamine.Supported by grants from Indian Council of Medical Research (ICMR), New Delhi. RIA kits for the estimation of LH, FSH and Prl were kindly supplied by Dr A.F. Parlow, NIAMDD-NIH, Bethesda, Maryland, USA. GNB is a UGC research fellow.     

Strain differences in the pattern and intensity of wheel running activity in laboratory rats

Summary Wheel running activity rhythms of three inbred rat strains, ACI/Ztm, BH/Ztm, and LEW/Ztm, were compared in order to evaluate the effect of genetic differences on circadian rhythm parameters. Significant strain differences were found in the general pattern of the activity rhythms and their characteristic periodicities as well as in the amount and duration of wheel running activity and the timing of activity onsets and offsets. The results suggest that genetic differences exist in the coupling of the multiple circadian oscillators that generate the overall pattern of wheel running activity.     

Asymmetry in the link between the yield spread and industrial production: threshold effects and forecasting

We analyse the nonlinear behaviour of the information content in the spread for future real economic activity. The spread linearly predicts one‐year‐ahead real growth in nine industrial production sectors of the USA and four of the UK over the last 40 years. However, recent investigations on the spread–real activity relation have questioned both its linear nature and its time‐invariant framework. Our in‐sample empirical evidence suggests that the spread–real activity relationship exhibits asymmetries that allow for different predictive power of the spread when past spread values were above or below some threshold value. We then measure the out‐of‐sample forecast performance of the nonlinear model using predictive accuracy tests. The results show that significant improvement in forecasting accuracy, at least for one‐step‐ahead forecasts, can be obtained over the linear model. Copyright © 2004 John Wiley & Sons, Ltd.     

Dopamine-beta-hydroxylase activity in adrenal gland and spleen of rats after fasting and cold exposure

Summary Fasting (48 h) results in dopamine-beta-hydroxylase (DBH) release both in adrenal gland and spleen, suggestive of an increase in the activity of these organs. Cold exposure (48 h) produces a dissociation of the, sympathoadrenal response. When both stimuli are simultaneously employed, the DBH response suggests the preponderance of the response to fasting. Plasma DBH is decreased in all groups studied, this could be due to its half-life and the splenic DBH depletion.This work was supported by a grant of Fondo de Investigaciones Sanitarias de la Seguridad Social, No. 83/0905.     

Influence of age,sex and glandular extirpation on muscle carcinogenesis in rats

Résumé Nos recherches sur la carcinogénèse du muscle strié par le sulfure de nickel chez des rats d'âge et de sexe différents et après extirpation des gonades on de l'hypophyse ont démontré que: (1) la fréquence, l'apparition et la progression des tumeurs étaient au plus haut niveau chez les femelles de 60 jours; (2) la castration chez les mâles, et à un degré moindre chez les femelles, réduisait à la fois la fréquence et la croissance tumorale; (3) l'hypophysectomie exerce une action freinatrice mais n'empêche pas nécessairement la tumorogénèse.

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This investigation has been supported by a grant from the National Cancer Institute of Canada.     

Influence of extra sucrose,fats, protein and of cyclamate in the daily food on the life-span of rats

Résumé Une quantité supplémentaire de 15 Cal/100 Cal de viande maigre sèchée ou de beurre dans un régime humain typique diminue la durée de vie du rat Wistar par comparaison avec des témoins et des animaux qui avaient reçu dans leur régime une quantité supplémentaire de sucre ou d'huile de tournesol. La durée de vie de ces derniers groupes fut la même. Un autre groupe qui avait reçu dans son régime de cyclamate de sodium au lieu de 2/3 de la quantité normale de sucre présenta un poids plus élevé et une durée de vie plus longue que les autres groupes.     

Spontaneous activity of rats on diets varied in protein,carbohydrate and fat content

Résumé Nous avons mesuré l'activité spontanée de rats mâles et femelles recevant des rations contenant 10%, 25% et 60% de protéine et 29% de graisses non-saturées ou 31% de graisses saturées. Les rats ont été maintenus isolés dans des cages à stabilimètre 6 jours de suite. On a comparé les données obtenues pendant les 3 derniers jours. On n'a pas trouvé de différences significatives dans l'effet des différents régimes, ni pour les mâles ni pour les femelles.

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This work was supported in part by a grant from the National Institute of Neurological Diseases and Blindness, No. NB 01941, of the National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland, and the Fund for Research and Teaching of the Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.