Publications by authors named "Fibiger H"

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.

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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.

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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.

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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.

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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.

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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.

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It has been suggested that noradrenaline in the central nervous system is involved in fear and anxiety. To test this postulate extensive depletion of ascending noradrenaline systems was accomplished by intracerebral injection of the selective neurotoxin 6-hydroxydopamine. Fear and anxiety were assessed using a Sidman avoidance task and a conditioned emotional response paradigm.

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Intracerebral injection of 4 microgram of the neurotoxin 6-hydroxydopamine (6-OHDA) was used to deplete forebrain noradrenaline (NA) in rats to less than 5% of control values without affecting brain dopamine (DA) and the oral consumption of ethanol examined. Control rats showed a progressive increase in their intake of a 15% ethanol solution and after 15 days were consuming large quantities. This increase did not occur in NA depleted rats, which after 15 days had consumed no more than a few millilitres of the solution in total.

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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.

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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.

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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.

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The selective neurotoxin 6-hydroxydopamine was used to deplete forebrain noradrenaline to less than 5% of control values and the learning capabilities of the depleted animals examined on a two-way active avoidance task. Noradrenaline depleted animals learned the two-way active avoidance task more quickly than controls and required fewer training trials to reach acquisition criterion. Twenty-four hour retention was not altered by the lesion, but significant resistance to extinction was seen when electric footshock was no longer presented.

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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.

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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.

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Widespread depletion of forebrain noradrenaline, produced by the intracerebral injection of 4 microgram of 6-hydroxydopamine into the fibres of the dorsal noradrenergic bundle, potentiated the catalepsy induced by 20 mg/kg of morphine and severely attenuated the catalepsy induced by two separate cholinergic agonists, arecoline and pilocarpine. It did not, however, affect haloperidol catalepsy at any of the four doses tested. These results suggest that cholinergic catalepsy may be critically dependent on an intact noradrenergic substrate, perhaps through cholinergic receptors located either presynaptically on noradrenergic terminals or on the cell bodies of origin in the locus coeruleus.

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