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Biomedical subjects

H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 271 records · Page 15Linked to original sources
PubMed1978

Kainic acid lesions of the striatum: behavioural sequalae similar to Huntington's chorea.

Kainic acid (3 nmoles bilaterally) was injected into the dorsal striatum of the rat producing virtually complete destruction of cell bodies in this structure but without directly affecting the dopamine terminals ascending from the substantia nigra and terminating in the striatum. Other fibres of passage, such as the internal capsule, were also spared. The locomotor and stereotypy responses to doses of amphetamine, a dopamine releasing agent, were found to be consistently enhanced after this lesion. The stereotypy and locomotor activity in response to the direct receptor agonist, apomorphine, however were not consistently affected. The results are interpreted in terms of a functional dichotomy between dorsal and ventral striatum and in terms of previously demonstrated electrophysiological alterations in the striatonigral feedback loop after kainic acid injection. Similarities are noted with the effects of these two stimulant drugs in human patients with Huntington's disease, thus strengthening the kainic acid animal model of this disease, first proposed on biochemical grounds.

Animals↗
PubMed1978

Kainic acid lesions of the striatum dissociate amphetamine and apomorphine stereotypy: similarities to Huntingdon's chorea.

Kainic acid lesion of cell bodies in the dorsal striatum enhanced the stereotypy-producing effects of d-amphetamine without affecting the sterotypy produced by the direct receptor agonist apomorphine. This pattern of results parallels that found in patients suffering from Hungtington's chorea, thus strengthening the parallels between the kainic acid animal model and the human disease state initially suggested on biochemical gounds. The present results further suggest a dissociation of the mechanisms involved in the production of stereotypy by these two drugs, perhaps in terms of differential involvement of the striato-nigral negative feedback loop.

Animals↗
PubMed1978

The use of kainic acid in the localization of enzymes in the substantia nigra.

The selective destruction of neuronal perikarya via intracerebral injections of kainic acid was used to elucidate the cellular location of four neurotransmitter-related enzymes in the substantia nigra (SN). Two weeks after intranigral injections of kainic acid, dopamine-sensitive adenylate cyclase, glutamic acid decarboxylase (GAD), choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were measured in the SN. Histological examination of the SN, and a reduction of striatal tyrosine hydroxylase (TH) activity by 94%, confirmed the extensive loss of neuronal cell bodies in the SN. Dopamine stimulation of adenylate cyclase was not reduced in the lesioned SN, supporting the view that dendritically-released dopamine can regulate cyclic AMP synthesis in afferent terminals to these dendrites. Nigral GAD activity was significantly reduced by the lesions, suggesting that there are GAD-containing perikarya in the SN. CAT activity was not affected by the kainic injections, indicating the absence of cholinergic perikarya in the SN. Nigral AChE activity was significantly decreased after kainic injections, thus confirming the presence of AChE within the nigral perikarya. The results suggest that dopamine-sensitive adenylate cyclase and CAT are located within afferents to the SN, while GAD and AChE are found, to some extent at least, in neuronal soma of the SN. The differentail effects of kainic acid on these enzymes suggest that this compound may be a useful neurochemical tool with which to determine the cellular distribution of enzyme systems in the central nervous system.

Acetylcholinesterase↗
PubMed1978

An analysis of dorsal and median raphe self-stimulation: effects of parachlorophenylalanine.

The role of serotonergic systems in intracranial self-stimulation (ICSS) of the dorsal and median raphe nuclei of rats was investigated. Intragastric administration of 400 mg/kg of parachlorophenylalanine (PCPA) depressed ICSS rates in the group with dorsal raphe electrode placements over a similar time course to the depletion of brain serotonin which results from treatment with PCPA. An intrasessional analysis of these behavioral changes on the fourth day after PCPA revealed that dorsal raphe ICSS was depressed over both halves of the 2 hr test session, whereas a significant depression in median raphe ICSS occurred only in the last hr of the session. The data from these studies suggest that brain serotonin systems contribute to the phenomenon of brain-stimulation reward in the dorsal and median raphe nuclei. The involvement of multiple neurochemical substrates of brain stimulation reward is discussed.

Animals↗
PubMed1978

Noradrenaline and partial reinforcement in rats.

Lesions of the dorsal nonadrenergic bundle produced by 6-hydroxydopamine, which depleted telencephalic noradrenaline by over 95%, were found to produce resistance to extinction in animals trained on a continuously reinforced schedule for food reward but not to alter the extinction rate after partial reinforcement training. These results confirm the dorsal bundle extinction effect reported previously but suggest that it is confined to continuously reinforced situations. The pattern of results is consistent with a role for the dorsal bundle in attentional processes but appears to contradict the predictions required if the dorsal bundle were to have a role in frustrative nonreward.

Animals↗