Biomedical subjects

H C Fibiger

Publications and source records attributed to H C Fibiger.

347 records · Page 20Linked to original sources

PubMedDate not supplied

Discriminated escape learning and response to electric shock after 6-hydroxydopamine lesions of the nigro-neostriatal dopaminergic projection.

In an earlier report it was observed that bilateral stereotaxic injections of 6-hydroxydopamine (6-OHDA) into the zone compacta of the substantia nigra deficits in the acquisition of a conditioned avoidance response [8], The present experiments were designed to determine if either a generalized learning impairment or a decreased sensitivity to foot shock might be the basis for the avoidance deficit. It was found that rats subjected to bilateral 6-OHDA lesions of the substantia nigra learned a light discrimination shock escape habit in as few trials as unoperated controls. This observation indicates that the integrity of the dopaminergic nigro-neostriatal system is not essential for the formation of learned associations between sensory cues and motor responses. In a second experiment it was observed that neither the shock-induced flinch nor the jump threshold was elevated after nigral lesions, suggesting that these lesions do not decrease the aversive motivational properties of foot shock. In view of these findings, the nature of the avoidance deficit produced by substantia nigra lesions is discussed with reference to the possibility that they selectively block the initiation of voluntary motor responses. According to this hypothesis, the failure of these lesions to disrupt escape responding may be due to the fact that the unconditioned stimulus generates reflexive motor responses (flinch, jump, etc.) which are sufficient to begin the motor sequences that cannot be initiated voluntarily in response to the conditioned stimulus.

Animals↗

PubMedDate not supplied

Chronic desipramine alters stress-induced behaviors and regional expression of the immediate early gene, c-fos.

This experiment examined the effects of acute or chronic administration of the antidepressant drug desipramine on conditioned stress-induced behaviors and regional c-fos expression in the brain. To this end, rats were exposed to three sequential daily sessions of uncontrollable foot-shock and matched, on the basis of crouching, into one of four groups. Two of these groups were exposed to saline injections twice daily and two were exposed to injections of desipramine (5 mg/kg, SC) twice per day, for 9 days. On the 10th day one of the saline groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Likewise, on the 10th day one of the desipramine groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Detailed behavioral analysis showed that compared to the saline-treated controls only the group treated chronically with desipramine, including on the test day, exhibited statistically significant reductions in crouching and increases in exploration during the test session. Similarly, Fos immunohistochemistry revealed that the chronic desipramine group showing positive behavioral effects was the only group in which there were significant reductions in the number of stress-induced Fos-positive neurons in five of 60 structures surveyed. These structures included the anterior cingulate cortex, anterior claustrum, central nucleus of the amygdala, dentate gyrus of the dorsal hippocampus, and paraventricular nucleus of the thalamus. To the extent that repeated exposure to uncontrollable stress is an animal model of depression, these and previous results suggest that these structures are potentially important neural targets for the antidepressant effects of desipramine.

Animals↗

PubMedDate not supplied

Nigrothalamic projections in the rat as demonstrated by orthograde and retrograde tracing echniques.

The nigrothalamic projection of the rat was investigated by means of horseradish peroxidase (HRP) histochemistry and by the autoradiographic tracing technique. The use of these techniques has permitted an extension of previous descriptions by identifying a neuron population in the substantia nigra, pars reticulata (SNR) as the nigrothalamic cells of origin. These calls (20-25 mu) were multipolar and were distributed throughout the SNR. There was a tendency however for more labelled neurons to be observed in the rostrolateral aspects of the nucleus. HRP-labelled neurons comprised roughly one-sixth of SNR neurons of comparable size, ventromedial (VM) thalamic nucleus. In addition, a smaller projection to the ipsilateral parafascicular nucleus was observed. The possible functional sifificance of the nigrothalamic projections is discussed in the light of recent anatomical, physiological and behavioral findings.

Animals↗

PubMedDate not supplied

Neurochemical correlates of brain-stimulation reward measured by ex vivo and in vivo analyses.

Evidence from ex vivo analyses of dopaminergic function following self-stimulation behavior is reviewed and compared to in vivo analyses of extracellular dopamine measured by chronoamperometry during self-stimulation. Both data bases provide strong support for a dopaminergic substrate for brain-stimulation reward obtained by electrical stimulation of the ventral tegmental area (VTA). Data obtained from in vivo measures of dopamine release are particularly compelling as a positive correlation was observed between the rate/intensity function for self-stimulation and increments in the oxidation current for dopamine. An examination of the effects of the dopamine uptake blockers, cocaine and GBR 12909 on self-stimulation and stimulated release of dopamine revealed a facilitation of both measures. In contrast, the noradrenaline uptake blocker desipramine had no effect on either self-stimulation or extracellular dopamine. These pharmacological experiments also are consistent with a dopaminergic substrate of brain-stimulation reward at electrode sites in the VTA.

Animals↗

PubMedDate not supplied

Substance P in the ascending cholinergic reticular system.

The neocortex receives a major cholinergic innervation from magnocellular neurones in the basal forebrain. However, an ascending cholinergic reticular system has also been postulated to arise from acetylcholinesterase (AChE)-containing neurones in the midbrain and pontine tegmentum. Lesions of this region decrease both AChE and choline acetyltransferase (ChAT) in various forebrain areas, and recent immunohistochemical studies have identified a group of ChAT-containing cell bodies in the midbrain reticular formation and dorsolateral pontine tegmentum. Here we have combined retrograde tracing with ChAT immunohistochemistry to demonstrate that this tegmental cholinergic cell group also directly innervates the cerebral cortex. Other immunohistochemical studies have indicated that the neuropeptide substance P is also present in certain cells in the laterodorsal tegmentum, and these too appear to project to the forebrain. We have therefore performed immunohistochemistry for both ChAT and substance P and have discovered that a subpopulation of the ascending cholinergic reticular neurones contains substance P. Thus, peptide-cholinergic coexistence, previously noted in peripheral neurones, also occurs in the brain.

Acetylcholine↗