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Biomedical subjects

H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 217 records · Page 12Linked to original sources

Demonstration of a pallidostriatal pathway by retrograde transport of HRP-labeled lectin.

A projection from the globus pallidus (GP) to the striatum in the rat was demonstrated by a retrograde tracer technique. After injections of lectin-conjugated horseradish peroxidase (WGA-HRP) which were wholly confined to the striatum, the GP exhibited reaction product characteristic of both retrograde and anterograde transport of marker. Electron microscopic examination of the GP confirmed the presence of both perikaryal and terminal labeling. Coinjection of kainic acid and WGA-HRP into the striatum blocked the appearance of anterograde label in the GP but the retrogradely labeled pallidal neurons remained visible.

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Conditioned defensive burying: a new paradigm for the study of anxiolytic agents.

Behavioral paradigms that have been designed to mimic forms of learning that are important for the survival of animals in the wild, rather than to minimize the contributions of adaptive predispositions, may prove to be particularly useful for studying the behavioral effects of drugs. In the present experiments, the propensity of rats to bury sources of aversive stimulation was disrupted in a dose-dependent fashion by a single injection of the anxiolytic drug, diazepam. This suggested that the conditioned defensive burying paradigm could prove to be a valuable addition to the paradigms available for studying anxiolytic effects. Supporting this view were two additional observations. First, the relative potencies of diazepam, chlordiazepoxide, and pentobarbital in the burying paradigm compared favorably with their relative potencies in clinical settings. Second, the effects of anxiolytics on conditioned burying appeared to be dissociable from the effects of other drugs that disrupt this behavior.

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Spontaneously recurrent seizures after intracerebral injections of kainic acid in rat: a possible model of human temporal lobe epilepsy.

Intrastriatal injection of kainic acid in rats acutely induced repeated episodes of clonic convulsions. Spontaneously recurrent generalized seizures and a potentiation of the convulsant effects of phentylenetetrazol were then observed in most of the injected rats several weeks after surgery. In addition to marked loss of striatial neurons, limbic pathological alterations similar to those found in human temporal lobe epilepsy were observed in the brains of the kainic-acid treated rats. It is proposed that this preparation might serve as an animal model of human temporal lobe epilepsy.

Animals↗

Neurotransmitters contained in the efferents of the striatum.

The transmitters contained in the efferent projections of the striatum were studied by producing two types of lesions: coronal hemitransections just anterior to the globus pallidus, and semi-circular knife cuts that isolated a considerable portion of the globus pallidus from the striatum to produce 'GP islands'. The levels of substance P and Met-enkephalin in the globus pallidus, entopeduncular nucleus and substantia nigra were measured after these lesions. For comparison, the effect of these lesions on glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) in some of these projection areas of the striatum was assessed. Both lesions caused similar reductions in substance P levels in each of the three striatal projection areas. In contrast, hemitransections reduced Met-enkephalin levels only in the globus pallidus. Both lesions reduced pallidal and entopeduncular GAD activity while nigral GAD activity was reduced only by the hemitransections. CAT activity was reduced in the globus pallidus by both lesions but was unaltered in the entopeduncular nucleus. However, additional experiments ruled out the existence of a striato-pallidal cholinergic projection. GAD activity and Met-enkephalin levels were significantly increased in the striatum anterior to the lesions. In contrast, CAT activity and substance P levels did not change in this region. The results support and broaden emerging view of the organization of the neurons containing the various transmitter candidates of the efferent projections of the striatum.

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Modulation of rat brain alpha- and beta-adrenergic receptor populations by lesion of the dorsal noradrenergic bundle.

Bilateral lesion of the ascending noradrenergic fibers in the dorsal bundle of adult Wistar rats with 4 micrograms 6-hydroxydopamine caused extensive depletion of norepinephrine in all forebrain areas, but led to a 54% increase in norepinephrine levels in the cerebellum. beta-Adrenergic receptor binding of [3H]dihydroalprenolol was significantly increased in all forebrain areas depleted of norepinephrine except hypothalamus. The increase in [3H]dihydroalprenolol binding was due to 62% and 34% increases in the number of beta-receptor sites in the frontal cerebral cortex and hippocampus respectively. Binding of [3H]WB-4101 to alpha 1-adrenergic receptors after dorsal bundle lesion was augmented generally to a lesser extent than beta-receptor binding, with significantly increased numbers of sites only in the frontal cortex (74%), thalamus (20%) and septum. Both alpha 1- and beta-receptor binding sites were reduced in number by 25-28% in the cerebellum of dorsal bundle-lesioned rats, whereas intraventricular administration of 6-hydroxydopamine to adult rats, which depletes norepinephrine in the cerebellum by 96%, increased cerebellar alpha 1- and beta-receptor binding by 33-40%. Binding of [3H]clonidine to forebrain alpha 2-adrenergic receptors was significantly elevated in the frontal cortex, but reduced in the amygdala and septum, after dorsal bundle lesion.

Amygdala↗

Neurotoxic action of capsaicin on spinal substance P neurons.

The effects of capsaicin injections into neonatal rats on the ultrastructure of the neonatal dorsal horn and on some biochemical and behavioral parameters in the adult were examined. Electron microscopic observations revealed degeneration and glial engulfment of boutons and umyelinated axons in the dorsal horn 2 and 6 h after neonatal subcutaneous capsaicin injections. Capsaicin treatment had no effect on the activities of glutamic acid decarboxylase and choline acetyltransferase in the dorsal horn. Results of substance P measurements in the CNS showed no effect of capsaicin administration on striatal, hypothalamic or nigral substance P content, whereas substance P levels in the dorsal horn of the spinal cord were reduced by half. The density of [3H]naloxone binding sites in the dorsal horn was significantly reduced, while the affinity was not affected. Capsaicin-treated animals showed significantly increased latencies to respond to a noxious thermal stimulus in both tail-flick and hot-plate tests. The results are discussed in relation to the current concepts of the involvement of substance P and opiate systems in nociception and the potential use of neonatal capsaicin as a selective neurotoxin for the elucidation of the spinal mechanisms of pain.

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Experimental influences on catalepsy.

Normal saline-injected rats were tested repeatedly on a standard catalepsy test. With repeated testing the animals showed a progressive increase in their catalepsy scores. It is suggested that this behaviour may be a form of tonic immobility and should be controlled for in catalepsy experiments.

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