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H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 19 recordsLinked to original sources
PubMed1979

The localization of receptor binding sites in the substantia nigra and striatum of the rat.

Neurotransmitter receptor binding of 5 ligands was examined in the striatum, substantia nigra (SN) and frontal cortex of rats which had received either unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway (NSP) or unilateral kainic acid lesions of the striatum. 6-OHDA lesions of the NSP significantly reduced [3H]dihydroalprenolol ([3H]DHA) and [3H]naloxone ([3H]Nal) binding by 31% and 28% respectively, in the denervated striatum compared to the contralateral side. Scatchard analysis revealed that the alteration in [3H]DHA binding was not due to a change in the affinity of the beta-adrenergic receptor for [3H]DHA. In marked contrast to these changes in the striatum, destruction of the NSP resulted in a significant increase in [3H]DHA and [3H]Nal binding by 44% and 26%, respectively, in the frontal cortex of the lesioned compared to the control side. 6-OHDA lesions in the NSP did not alter striatal receptor binding for [3H]quinuclidinyl benzilate ([3H]QNB), [3H]muscimol ([3H]Mus) or [3H]flunitrazepam ([3H]Flu). Similarily, intrastriatal kainic acid injections did not alter striatal receptor binding for [3H]Nal, [3H]Flu or [3H]Mus. Of the various receptor densities measured in the SN after the above lesions the only alteration observed was a 43% increase in [3H]Flu binding following 6-OHDA lesions of the NSP. Scatchard analysis indicated no change in the affinity of the benzodiazepine receptor for [3H]Flu. 6-OHDA lesions of the NSP did not alter [13H]QNB or [3H]Nal binding in the SN. Striatal kainic acid lesions did not alter nigral [3H]QNB or [3H]Flu binding. The results are discussed in terms of neurotransmitter localization and plasticity within the striatum, SN and frontal cortex.

Animals↗
PubMed1979

Regional topography within noradrenergic locus coeruleus as revealed by retrograde transport of horseradish peroxidase.

A hitherto unsuspected degree of regional topographic organization in the noradrenergic nucleus, locus coeruleus, was revealed by the use of retrograde transport of horseradish peroxidase (HRP) from terminal areas receiving noradrenergic innervation. HRP was injected into hippocampus, hypothalamus, thalamus, caudate-putamen, septum, amygdala-piriform cortex, cerebellum and cortex. Successful transport was obtained from all areas, including the caudate-putamen and cerebral cortex. The pattern of HRP positive cells in the ipsilateral locus coeruleus was markedly different depending on the location of the HRP injection. Thus, hippocampal injections labeled cells in the dorsal locus coeruleus but not at all in the ventral tip. Injections of HRP into caudate-putamen or cerebellum labeled the ventral tip along with the rest of the dorsal portion. HRP injections into the septum labeled cells only in the dorsal half of the dorsal locus coeruleus. There thus exists a three tier division of locus coeruleus into the ventral one third, dorsal one third and intermediate one third. A further division was seen in the anterior-posterior plane with HRP injections into the thalamus labeling the posterior pole of locus very intensely but with little transport to more anterior levels; conversely HRP injection into the hypothalamus resulted in intense labeling only in the anterior pole of locus coeruleus. Amygdala-piriform cortex HRP injections revealed a further pattern with very intensely reactive cells scattered sparsely throughout the nucleus. Cortical HRP injections yielded weaker labeling also in occasional, scattered cells. All HRP transport to locus coeruleus was shown to be noradrenergic by degeneration with 6-hydroxydopamine and due to terminal, rather than fiber of passage, uptake by control injection into the dorsal NA bundle. It is concluded that the locus coeruleus is not an homogenous nucleus with respect to the origin of the noradrenergic projections to sundry forebrain, spinal and cerebellar areas but is comprised of distinct subdivisions of noradrenergic neurons.

Amygdala↗
PubMed1979

Physiological function of descending noradrenaline projections to the spinal cord: role in post-decapitation convulsions.

Destruction of the descending noradrenergic innervation to the spinal cord, but not that to the cerebellum or the forebrain, by the use of intracerebral injection of 6-hydroxydopamine completely prevented the occurrence of the usual itation convulsion. Depletion of brain noradrenaline by synthesis inhibition with DDC, FLA 57 or FLA 63 g reduced the duration of the post-decapitation convulsion. Blockade of alpha-noradrenergic receptors by phentolamine or phenoxybenzamine, but not of beta-receptors by propranolol, also reduced the duration of the convulsion. The presynaptic alpha-agonist, clonidine, at either 1 mg/kg or 0.05 mg/kg also reduced the magnitude of the convulsion but either blockade of dopamine receptors with pimozide or destruction of the ascending dopamine systems by 6-hydroxydopamine was without effect. It is concluded that dopamine systems are not involved in post-decapitation convulsions and that the noradrenergic involvement is by the descending spinal projections acting on a post-synaptic alpha-receptor in the spinal cord, but also modulated by presynaptic alpha-receptors possibly on the locus coeruleus perikarya.

Animals↗
PubMed1979

On the specificity of kainic acid.

The specificity of the neurotoxic agent, kainic acid, for destroying cell bodies while sparing terminals and fibers of passage was examined by infusing this agent into the axons of the dorsal noradrenergic bundle and measuring the degree of depletion of noradrenaline concentrations and the reduction in noradrenaline uptake in cortex and hippocampus. Extensive neuronal loss and gliosis were observed around the injection site. In addition, a significant and consistent 25 percent depletion of hippocampal-cortical noradrenaline was also obtained. The results suggest that although kainic acid has its greatest destructive action on neuronal perikarya, a significant amount of damage to axons of passage may also occur.

Adrenergic Fibers↗
PubMed1979

The dorsal bundle extinction effect:dependence on subtle changes in acquisition.

Destruction of the ascending noradrenergic innervation to the forebrain in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine (4 microgram in 2 microliter injected bilaterally into the dorsal bundle in the mesencephalon) was found to cause resistance to extinction of a continuously reinforced lever press response. However, this effect occurred only if the lesion were present during acquisition training on the reinforced schedule and not if intact animals were trained and the lesion inflicted after completion of acquisition training and just prior to the extinction phase. Thus, the behavioural effect that manifests itself during extinction appears to be due to subtle changes in the acquisition learning process. This is consistent with the predictions of an attentional theory of noradrenergic function and appears to exclude most other suggested explanations of the dorsal bundle extinction effect.

Animals↗
PubMed1979

Impaired acquisition and retention of a passive avoidance response after chronic ingestion of taurine.

Oral administration of taurine (0.9%) in the drinking water resulted in impairment of acquisition and, to a lesser extent, retention of a step-down passive avoidance task in rats. No effect was found on spontaneous locomotor activity or habituation measured in photocell activity cages. There were also no differences observed in either the taurine-treated or control rats in their sensitivity to electric shock. These observations suggest that the administration of oral taurine may have adverse effects on inhibitory or memory functions.

Animals↗
PubMed1979

Noradrenergic processes involved in the locomotor effects of ethanol.

Male albino Wistar rats were depleted of forebrain noradrenaline by intracerebral injection of 4 microgram of 6-hydroxydopamine into the noradrenaline bundles in the mesencephalon. The locomotor response was examined in response to intraperitoneal injection of ethanol. The locomotor stimulation by 0.1 g/kg ethanol was not altered by the lesion, whereas the sedation found in response to 1 g/kg in controls failed to occur in the lesioned rats and instead a stimulation was seen.

Animals↗
PubMed1979

Sedative effects of apomorphine in an animal model of Huntington's disease.

The sedative effectiveness of apomorphine in a newly developed animal model of Huntington's disease was examined. The motor responses of rats with kainic acid lesions of the neostriatum to a sedative dose of apomorphine (50 micrograms/kg) was similar to that observed in intact controls. In contrast, compared to controls, a marked potentiation of the motor stimulant effects of dextroamphetamine was confirmed in the kainic acid-lesioned group. We suggest that the pathological changes underlying the symptoms observed in this animal model and in Huntington's disease do not include abnormalities in presynaptic dopamine receptors in the neostriatum.

Animals↗
PubMed1979

The dorsal noradrenergic bundle and varieties of passive avoidance.

Neither acquisition learning nor 24-h retention was significantly altered by 6-hydroxydopamine intracerebral injections which depleted forebrain noradrenaline (NA) to less than 5% of control values. The absence of passive avoidance impairment cannot be ascribed to functional recovery following the lesion (indicated by testing 24 h post-operation) and by using the F-344 strain of rat which does not show denervation supersensitivity as measured by NA-sensitive adenylate cyclase. Nonassociative freezing to electric footshock, changed by the injections, resulted in slower acquisition at a footshock level 4 mA, but not at 1 mA.

Adenylyl Cyclases↗
PubMed1979

Interaction of brain noradrenaline and the pituitary-adrenal axis in learning and extinction.

The effect of 6-hydroxydopamine-induced degeneration of the dorsal tegmental noradrenergic (NA) projection alone or in combination with the removal of the adrenal glands was examined on several behavioral tasks. No impairment of acquisition on a continuously reinforced lever pressing response for food reward was seen as a result of the combined treatment. However, resistance to extinction was observed after depletion of forebrain noradrenaline on its own and this effect was prevented by the adrenalectomy. Adrenalectomy on its own failed to affect extinction. Acquisition of a passive avoidance task was slightly impaired after forebrain noradrenaline depletion but only the group with combined noradrenaline loss and adrenalectomy showed a 24 hour retention deficit. No alteration in shock thresholds was found in any group although both adrenalectomized groups consumed less food and were slightly less active in locomotor cages. It is suggested that previous reports of acquisition and retention deficits in avoidance tasks after combined dorsal NA bundle lesions and adrenalectomy are due to alterations in fear motivation rather than to a general learning impairment.

Animals↗
PubMed1979

Avoidance, operant and locomotor behavior in rats with neostriatal injections of kainic acid.

Compared with saline injected controls, rats with bilateral injections of kainic acid (KA) in the dorsal neostriatum showed increased locomotor response to d-amphetamine, increased resistance to extinction and impaired acquisition and retention of passive avoidance. The KA injection resulted in loss of local neurons in the dorsal neostriatum, with no appreciable damage either to dopaminergic terminals or to extrinsic myelinated axons, thus supporting both the selective neurotoxic action of KA on neuronal perikarya and the proposed similarity of KA-induced neostriatal lesions with those found in the caudate-putamen of patients with Huntington's disease. Although loss of hippocampal neurons was occasionally observed, the behavioral results could not be wholly attributed to hippocampal damage, since rats with no demonstrable extrastriatal lesions were not less impaired than those with hippocampal damage. An altered arousal reaction to stressful situations might account for the learning and memory impairments of the KA neostriatal rats.

Animals↗
PubMed1979

Neurochemical basis of the dorsal bundle extinction effect.

Injection of 6-hydroxydopamine into the mesencephalon of the rat has been found to cause resistance to extinction on continuously reinforced schedules. The neurochemical basis of this effect was investigated by using another concentration of 6-hydroxydopamine and by another position of injection. Severe depletion of forebrain noradrenaline was found after these injections with no change in dopamine, serotonin, cholinergic or GABAergic parameters in any brain area measured. The noradrenergic nature of the effect was further shown by the reversal fo the usual behavioural effect following pretreatment with a noradrenaline uptake inhibitor (desimipramine, 25 mg/kg 30 min prior to intracerebral injection of 6-hydroxydopamine). This rules out non-specific damage caused by the 6-hydroxydopamine as the neurochemical basis of the dorsal bundle extinction effect. Failure to find resistance to extinction after either kainic acid or 5-7 dihydroxytryptamine injection seems also to exclude respectively cell body loss at the injection site or damage to serotonergic systems. It is concluded that the dorsal bundle extinction effect is noradrenergic in nature.

5,7-Dihydroxytryptamine↗