Actions of Neurotensin and (Gln4)-Neurotensin on Isolated Tissues

Abstract The actions of neurotensin and (Gln⁴)-neurotensin have been investigated on a number of isolated tissues. They were ineffective in contracting the guinea pig vas deferens, the rabbit aortic strip or the frog rectus abdominis muscle in concentrations up to 0.24 γM. Neurotensin and (Gln⁴)-neurotensin relaxed the rat duodenum at fairly high concentrations (24 nM). The guinea pig ileum contracted in response to increasing doses, although the maximum response were only one half that caused by histamine. Tachyphylaxis was observed at dose intervals of less than 12 minutes, but this tachyphylaxis did not inhibit responses to acetylcholine, histamine, 5-HT or to DMPP, suggesting that the neurotensins may act at specific receptor sites. They contracted the rat fundus strip at concentrations of 0.24 nM and higher. The neurotensins and 5-HT were approximately equipotent on this tissue, although the maximum respones was about 80 % of that to 5-HT. The contractions of the rat fundus strip could not be blocked by atropine, hexamethonium, methysergide, morphine or by 7-OH-THC. These data indicate that neurotensin and (Gln⁴)-neurotensin are equipotent as far as smooth muscle stimulating activity is concerned. Of those organs tested, the rat fundus strip seems to be the most suitable one for studies concerning structure-activity relationships.     

Multiple unit activity recorded from amygdala central nucleus during Pavlovian heart rate conditioning in rabbit

Using a Pavlovian heart rate conditioning paradigm, a rapid development of short latency increases in the multiple unit activity of the amygdala central nucleus were observed in response to a tone conditioned stimulus. In some cases the increases in multiple unit response showed a parallel development with the conditioned develerative heart rate response and were significantly correlated with it. These results suggest a direct role for the central nucleus in the expression of conditioned heart rate responding in rabbit.     

Effects of chronic reserpine treatment on development of maturity of the putamen in fetal rabbits

Developing nigrostriatal axons and their perikarya have substantial quantities of dopamine (DA) before the axons reach their postsynaptic target. In order to investigate possible developmental effects of these stores of DA, we have depleted DA chronically during critical periods in the ontogeny of the nigrostriatal system. Reserpine (0.04–0.14 mg/kg/day) was given repeatedly to maternal rabbits for various periods starting before neuroblasts of the substantia nigra first exhibit fluorescence until 2 days before term when the fetuses were sacrificed. Reserpine crossed the placenta and depleted DA in the fetal putamens. Control fetuses had widespread fluorescent axons and terminals. Counts of mature axonal boutons in electron micrographs of the putamen of reserpine-treated fetuses showed that there were 4.3 ± 0.6 SE/100 μm², which is less than the control value of 10.2 ± 0.6 SE/100 μm² (p < 0.001). The neuropil of the putamen of the reserpine-treated fetus was also less mature; the relative volume occupied by growth cones (40.5% ± 5.7 SE) was twice that of controls (20.6% ± 2.4 SE) (p < 0.005). Although it remains to be shown that the delayed development of both pre- and postsynaptic elements of the nigrostriatal system is specifically related to the known ability of reserpine to deplete DA, the results are consistent with the hypothesis that early stores of DA may be important in developing dopaminergic systems.     

VISUAL EVOKED POTENTIALS AS A MEASURE OF DRUG EFFECTS ON AROUSAL IN THE RABBIT

SUMMARY 1. Averaged evoked potentials in response to light flashes were recorded from the scalp in conscious, restrained rabbits. Six sedative and three stimulant drugs were administered intravenously and their effects on the evoked potential were measured
2. All six sedative drugs reduced the amplitude of the surface-negative wave occurring 150–200 ms after the stimulus, whereas all three stimulants increased the size of this component. No such consistency was found in drug effects on the early surface-positive wave.
3. The results obtained support the hypothesis that the size of certain components of sensory averaged evoked potentials is related to the level of behavioural arousal.     

Dopamine stimulation of passive permeability and secretion in the isolated rabbit ciliary epithelium.

Dopamine, at concentrations between 1·25 × 10^?7m and 1·25 × 10^?3m, increases both fluid secretion and passive fluid permeability across the isolated rabbit ciliary epithelium. These effects can be blocked by α- and β-adrenergic antagonists but not by specific dopaminergic antagonists. The present data suggest that dopaminergic receptors are not present in the ciliary epithelium.     

Taurine levels in developing rabbit brain and other organs

The levels of taurine in brain, heart, liver, kidney, spleen, muscle, and blood of rabbit were determined during development. Taurine was found to be present in a very high concentration at birth and to decrease during maturation in all parts studied except heart.     

Frequency-Dependence of the Metabolism of 3H-Noradrenaline Released from Rabbit Isolated Aorta: Effects of a Combination of Cocaine and Corticosterone or Hydrocortisone

Abstract The effect of cocaine (neuronal uptake inhibitor) in combination with either hydrocortisone or corticosterone (extraneuronal uptake inhibitors) on the metabolism of ³H-noradrenaline (³H-NA) released spontaneously or by electrical-field stimulation was studied on the isolated rabbit aorta preloaded with ³H-NA. In the spontaneous outflow ³H-O-methylated and deaminated metabolites (³H-OMDA) accounted for 41% of the total radioactivity whereas ³H-NA represented only 22%. Cocaine (3 × 10^-5M) + hydrocortisone (10^-4 M) neither changed the spontaneous outflow of total tritium nor the distribution of the ³H-outflow on ³H-NA and its ³H-metabolites. However, cocaine (3 × 100^-5M) + corticosterone (4 × 10^-5M) enhanced the passive ³H-outflow, increased the percentage recovered as ³H-3,4-dihydroxyphenylglycol (³H-DOPEG), and reduced the percentage of ³H-OMDA + ³H-NMN. The effect of field-stimulation was investigated during and ofter stimulation at two frequencies: 3 and 10 Hz. The stimulation-induced ³H-overflow consisted mainly of unmetabolized ³H-NA and ³H-OMDA in the sample collected during stimulation. The ratio between ³H-NA and ³H-OMDA was strongly dependent on the frequency of stimulation, Thus it was 1:2 at 3 Hz, but 3:1 at 10 Hz. These ratios were about the same during the poststimulation period. On the other hand, whereas the formation of ³H-DOPEG from ³H-NA released during stimulation at both frequencies was small, it increased rapidly in the poststimulation sample. At 3 Hz, inhibition of neuronal and extraneuronal uptake by cocaine + steroids did not change the stimulation-induced ³H-overflow, but the distribution on ³H-NA and ³H-metabolites was markedly altered. Thus the percentage of ³H-N A was doubled, ³H-OMDA was halved, and ³H-DOPEG was almost abolished. At 10 Hz, however, cocaine + corticosterone decreased the stimulation-induced ³H-overflow, but did not change the proportions of ³H-NA and ³H-OMDA. Only the formation of ³H-DOPEG was markedly reduced. It is concluded that the distribution of stimulation-induced ³H-overflow on ³H-NA and its ³H-metabolites and the effect of neuronal and extraneuronal uptake inhibition on this is strongly influenced by the frequency of stimulation. Furthermore, inhibition of both neuronal and extraneuronal uptake does not fully prevent metabolism of ³H-NA released by electrical-field stimulation.     

Computed tomography of the inner ear: size of anatomical structures in the normal temporal bone and in the temporal bone of patients with Menière’s disease

The purpose of the study was to obtain reference values for the sizes of anatomical structures of the inner ear on computed tomography (CT) images and to compare these values with those obtained from patients with Menières disease. CT images of the temporal bone of 67 patients without inner ear pathology and 53 patients with Menières disease have been evaluated. CT was performed in the sequential mode (1-mm slice thickness, 120 kV, 125 mA). Anatomical structures, such as the length and the width of the cochlea and of the vestibule, the height of the basal turn, the length and the width of the cochlear, the vestibular and the singular aqueduct and the internal auditory meatus and the diameter of the semicircular canals, were measured, using a dedicated postprocessing workstation. Reference values from the control group could be obtained. In the patients with Menières disease, the length and the width of the vestibular aqueduct were smaller, compared with the values from the control group. The values obtained from the control group can serve as reference values for adult patients. The different sizes of anatomical structures of the control group and of patients suffering from Menières disease suggest that functional impairment might be related to subtle morphological changes.     

Magnetic resonance techniques for the in vivo assessment of multiple sclerosis pathology: consensus report of the white matter study group

On October 9-11, 2003, the third meeting of the White Matter Study Group of the International Society for Magnetic Resonance in Medicine was held in Venice, Italy. This article is the report of the meeting on how to use MRI in the diagnostic workup of multiple sclerosis (MS) and allied white matter disorders, and to define the nature and the extent of MS pathology in vivo. Both of these steps are central to the design of future treatment strategies aimed at limiting the functional consequences of the most disabling aspects of this disease.