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H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 163 records · Page 9Linked to original sources
PubMed1986

Increased dopamine metabolism in the nucleus accumbens and striatum following consumption of a nutritive meal but not a palatable non-nutritive saccharin solution.

This study examined the concentrations of dopamine (DA) and its metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum and nucleus accumbens of rats that were either 20 hr food deprived or had been given 1 hr of access to food pellets, a liquid diet, or a palatable 0.4% saccharin solution. Significant increases were observed in the HVA/DA ratio in both structures following ingestion of either liquid diet or food pellets. Increases in the DOPAC/DA ratio were observed only after the ingestion of liquid diet. Ingestion of saccharin solution had no effect on any index of DA activity. These results indicate that the type of food ingested can influence dopaminergic responses to feeding, and argue against an exclusive role for motor or reward processes in determining DA activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Dopaminergic and serotonergic correlates of stimulation-induced circling.

Rotation induced by electrical stimulation of the medial forebrain bundle at the level of the lateral hypothalamus was associated with increases in dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum ipsilateral to the site of stimulation (i.e. contralateral to direction of turning). The concentrations of DA, DOPAC and HVA within the nucleus accumbens (NAS) were not altered. In the olfactory tubercle (OT), concentrations of DA and both metabolites were, in general, elevated ipsilateral to the electrode. However, relative to non-stimulated controls, HVA concentrations were increased bilaterally in rats exhibiting circling. Stimulation-induced circling also resulted in a bilateral enhancement of striatal serotonin (5-HT) metabolism as indicated by elevated 5-hydroxyindoleacetic acid: 5-HT ratios. No changes in 5-HT metabolism were observed in the NAS. The utilization of 5-HT was elevated in the OT ipsilateral to the electrode in rats that exhibited stimulation-induced rotation. While most subjects that exhibited contraversive rotation in response to the stimulation demonstrated enhanced DA activity, the neurochemical changes were not observed in all subjects. As such, it is concluded that while stimulation of the mesotelencephalic DA system can be associated with stimulation-induced rotation it is not necessary for its elicitation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

The localization of central cholinergic neurons.

Over the past decade our understanding of the localization of central cholinergic neurons has greatly increased. Interest in these systems has also intensified due to the involvement of cholinergic mechanisms in Alzheimer's disease. The distribution of central cholinergic neurons is reviewed, focusing on recent work in experimental animals. The pharmacohistochemical procedure for acetylcholinesterase and the development of antibodies to choline acetyltransferase are two of the major technical advances that have shaped our knowledge of the distribution of central cholinergic neurons. The results, advantages and limitations of both techniques are discussed. A discussion of the phenomenon of coexistence of acetylcholine with neuroactive peptides in central neurons is also included.

Acetylcholinesterase↗
PubMed1986

Neuropeptides and NADPH-diaphorase activity in the ascending cholinergic reticular system of the rat.

A major group of cholinergic neurons is present in the midbrain and pontine tegmentum. These cells could be selectively stained using either monoclonal antibodies to choline acetyltransferase, the pharmacohistochemical acetylcholinesterase procedure, or reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. Using these three techniques, the precise distribution of this cell group was determined. By combining these techniques with immunohistochemical staining for various neuropeptides, examples of peptide-cholinergic coexistence could be demonstrated in this cell group. Approximately 30% of these cholinergic neurons displayed substance P immunoreactivity. Most of these cells also showed corticotropin-releasing factor immunoreactivity and bombesin/gastrin-releasing peptide immunoreactivity. These results therefore provide evidence for the coexistence of various neuropeptides together with NADPH-diaphorase activity in the ascending cholinergic reticular system.

Acetylcholinesterase↗
PubMed1986

Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis.

The effects of bilateral ibotenic acid-induced lesions of the nucleus basalis magnocellularis (nBM) on the acquisition and retention of several spatial memory tasks were studied in the rat. Maintenance of spatial memory in a food search task was impaired following nBM lesions. Acquisition of spontaneous alternation and reinforced alternation in a T-maze was also significantly impaired in animals with these lesions. In contrast, the animals with nBM lesions were not impaired in the acquisition of a position habit in a T-maze. In several of the tasks there was evidence of some learning in the lesion animals after substantial training, although they were significantly deficient when compared with the controls. Administration of the cholinergic agonists physostigmine sulfate or pilocarpine nitrate prior to behavioral testing resulted in a rapid and significant improvement in the performance of the lesion animals. The ibotenate-induced lesions significantly reduced the activity of choline acetyltransferase (CAT) in the anterior and the posterior neocortex. Hippocampal CAT activity was not changed. The results indicate that the cholinergic projections originating in the nBM are involved in the learning and memory of spatial tasks.

Animals↗
PubMed1986

Bilateral augmentation of dopaminergic and serotonergic activity in the striatum and nucleus accumbens induced by conditioned circling.

The involvement of dopaminergic (DA) and serotonergic (5-HT) systems in circling was assessed by determining the neurochemical correlates of circling induced and maintained by two different schedules of water reinforcement. The conditioned circling paradigm was employed in an attempt to replicate reports that levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were increased in the striatum and nucleus accumbens septi (NAS) contralateral to the direction of circling. Rats trained to circle using a continuous schedule of reinforcement did not exhibit any changes in concentrations of DA, DOPAC, or homovanillic acid (HVA). Bilateral increases in 5-HT concentrations were observed in the striatum. Use of an intermittent schedule of reinforcement (FR-2) produced higher rates of circling. In rats maintained on the FR-2 schedule, no changes in DA or its metabolites were observed in the striatum. The ratio of HVA to DA was, however, increased bilaterally, suggesting a bilateral augmentation of DA utilization. Concentrations of DA were lower in the NAS contralateral to direction of turning. While NAS levels of HVA were elevated bilaterally when compared to non-circling controls, HVA was lower in the NAS contralateral to the direction of circling. DA utilization, as estimated by HVA: DA ratios, was increased bilaterally in the NAS. None of the measures of DA activity within the olfactory tubercle (OT) were influenced by circling. Turnover of 5-HT, as estimated by the ratio of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA), was increased bilaterally in the striatum, NAS, and OT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of bilateral ibotenate-induced lesions of the nucleus basalis magnocellularis upon selective cholinergic biochemical markers in the rat anterior cerebral cortex.

The relationship of choline acetyltransferase (ChAT) activity and high affinity binding of the potent and selective sodium-dependent choline uptake inhibitor [3H]hemicholinium-3 ([3H]HC-3) to high-affinity binding of the muscarinic agonist [3H](+)-cis-methyldioxolane ([3H](+)CD), the putative M1 selective antagonist [3H]pirenzepine ([3H]PZ) and the classical antagonist [3H](-)-quinuclidinyl benzilate ([3H](-)QNB) in homogenates of the rat neocortex was studied. ChAT activity was 42% lower in rats with ibotenate-induced lesions of the nucleus basalis magnocellularis (nbm) when compared to controls, and [3H]HC-3 binding was similarly reduced by 44%. However, equilibrium dissociation constants (Kd values) for [3H]HC-3 (0.8-1.0 nM), [3H](-)QNB (11-24 pM), [3H]PZ (4.0-4.3 nM) and [3H](+)CD (2.1-2.9 nM) were each unchanged. Mean Bmax values (total binding site densities) for [3H](+)CD were significantly altered in both hemispheres of the anterior cerebral cortex, showing a 25% reduction in the number of sites which display the highest affinity conformation for this potent muscarinic agonist. The decreased ChAT activity and [3H]HC-3 binding after nbm lesions were associated with only slight reductions in putative M1 muscarinic site density (14%) and [3H](-)QNB binding site density (13%). Thus, it appears that while [3H]PZ and [3H](-)QNB label predominantly postsynaptic muscarinic binding sites, a significant number of sites labeled by [3H](+)CD may be associated with presynaptic cholinergic nerve terminals. These data suggest that cholinergic input differentially regulates the drug binding sites of anterior cerebral cortical muscarinic receptors, exerting a substantial effect upon the highest affinity conformational state for agonists.

Acetylcholinesterase↗
PubMed1985

Distribution of central cholinergic neurons in the baboon (Papio papio). I. General morphology.

The morphological characteristics of cholinergic neurons in the central nervous system (CNS) of the baboon (Papio papio) were studied by choline acetyltransferase (ChAT) immunohistochemistry and acetylcholinesterase (AChE) pharmacohistochemistry. The distributions of central cholinergic neurons as visualized by these two histochemical techniques were similar in most, but not all regions of the brain and spinal cord. Based upon these observations, central cholinergic neurons that are immunoreactive to ChAT and intensely stained for AChE by the pharmacohistochemical procedure can be divided into four major groups: (1) those in the caudate nucleus, putamen, nucleus accumbens and anterior perforated substance. These ChAT-containing and AChE-intense neurons are large and multipolar, and are scattered throughout these structures. (2) The rostral cholinergic column, which consists of a continuous mass of cholinergic perikarya situated in the medial septal nucleus, nucleus of the diagonal band, and nucleus basalis (Meynert). The ChAT-immunoreactive and AChE-intense cell bodies of the nucleus basalis are a prominent feature in the basal forebrain of the baboon. The labeled neurons are large, multipolar, and hyperchromic and show a tendency to aggregate in cell clusters. These cells are distributed within the full extent of the substantia innominata, often being associated with subcortical fiber networks such as the medullary laminae of the globus pallidus. (3) The caudal cholinergic column, which consists of a continuous group of cholinergic neurons in the caudal midbrain and pontine tegmentum. The rostral component of this group of cells is the nucleus tegmenti pedunculopontinus (subnucleus compacta) and it extends caudally to include the laterodorsal tegmental nucleus. Compared to that in other species the nucleus tegmenti pedunculopontinus in the baboon appears to occupy a relatively greater volume and is composed of a greater number of cholinergic neurons. The cells of the caudal column are large and hyperchromic. (4) Nuclei of origin of somatic and visceral efferents of the cranial nerves (III, IV, V, VI, VII, IX, X, XI, XII) and spinal nerves. In addition to these major cholinergic cell groups, a small population of ChAT-positive and AChE-intense cell bodies can be observed at the floor of the fourth ventricle and in lamina VII and X of the cervical cord. The present findings indicate that although some differences exist, the overall distribution and morphological features of cholinergic cell bodies identified in the baboon brain and spinal cord are similar to those demonstrated previously in investigations of the rhesus monkey and nonprimates.

Acetylcholinesterase↗
PubMed1985

Distribution of central cholinergic neurons in the baboon (Papio papio). II. A topographic atlas correlated with catecholamine neurons.

The topographic distribution of central cholinergic and catecholaminergic neurons has been investigated in the baboon (Papio papio). The perikarya were mapped on an atlas through the brain and spinal cord employing sections processed for acetylcholinesterase (AChE) pharmacohistochemistry coupled with choline acetyltransferase (ChAT) immunohistochemistry or aqueous catecholamine-fluorescence histochemistry. Compared with subprimates, there is a remarkable increase in the volume occupied by and the number of cholinergic cells contained in the nucleus basalis and nucleus tegmenti pedunculopontinus (subnucleus compacta). The elaboration of these parts of the cholinergic system is accompanied by a large extension of catecholaminergic cell groups in the midbrain (groups A8-A10), particularly the substantia nigra (pars compacta), and in the dorsolateral pontine tegmentum (A5-A7 complex). Although cholinergic and catecholaminergic soma generally occupy distinctly different regions of the brain, a close apposition of cholinergic and noradrenergic neurons occurs in the dorsolateral pontine tegmentum. In the peripeduncular region ChAT-positive cells and green fluorescent neurons of the A6-A7 complex form parallel lines and do not intermingle as has previously been demonstrated in the cat. Two distribution patterns, aggregated or disseminated, are another common feature of central cholinergic and catecholaminergic perikarya. The cholinergic neurons in the nucleus tegmenti pedunculopontinus and the catecholaminergic neurons in A6-A7 complex display both patterns. This comparative study of three transmitter systems in the baboon suggests that the cholinergic as well as the catecholaminergic neurons that give rise to ascending telencephalic and dorsal diencephalic projections undergo phylogenetic development in terms of cell number and nuclear volume.

Acetylcholinesterase↗
PubMed1985

Place preference conditioning with methylphenidate and nomifensine.

The role of central catecholaminergic systems in place preference conditioning produced by methylphenidate and nomifensine was investigated. Several doses of either methylphenidate or nomifensine produced alterations in place preferences, while desipramine (10 mg/kg), a relatively selective noradrenergic uptake inhibitor, was ineffective, Haloperidol (0.15-0.5 mg/kg) did not attenuate place preferences induced with methylphenidate (2.5 and 5.0 mg/kg) or nomifensine (5.0 mg/kg), although conditioning with methylphenidate (5.0 mg/kg) was blocked after injections of a high dose of haloperidol (1.0 mg/kg). Intraventricular injections of 6-hydroxydopamine had no effect on methylphenidate (2.5 mg/kg) induced place preferences. In contrast, pretreatment with haloperidol (0.2 mg/kg) or intraventricular injections of 6-hydroxydopamine attenuated locomotor activity induced by methylphenidate (5.0 mg/kg). These results suggest that methylphenidate and nomifensine produce place preferences via mechanisms that are either qualitatively or quantitatively distinct from their catecholamine-dependent stimulant actions.

Animals↗
PubMed1985

The effects of progabide (SL 76002) on locomotor activity and conditioned place preference induced by d-amphetamine.

The effect of prior treatment with a GABA mimetic, SL 76002 (100 mg/kg i.p.), on amphetamine-induced locomotor activity and conditioned place preferences with amphetamine (1.5 mg/kg i.p.) was investigated. SL 76002 significantly attenuated the motor stimulant effects of amphetamine, without influencing the rewarding properties at least as determined by the place preference procedure. When injected alone, SL 76002 did not affect handling-induced locomotor activation, nor did it exhibit any aversive or reinforcing properties. The results suggest that separate neural systems may subserve the motor and rewarding properties of amphetamine.

Animals↗
PubMed1985

Learning and memory deficits after lesions of the nucleus basalis magnocellularis: reversal by physostigmine.

The role of the cholinergic nucleus basalis magnocellularis in spatial learning and memory was studied in the rat. Animals received bilateral injections of ibotenic acid (5 micrograms/microliters) into the region of the nucleus basalis magnocellularis. Six weeks postoperatively they were deprived of food and trained for 5 weeks in a 16-arm radial maze in which 9 of the arms were baited with food. The nucleus basalis magnocellularis-lesioned animals showed significant deficits in the acquisition of the task. Further analysis of the data indicated that this was due primarily to a deficit in reference (long-term) as opposed to working (short-term) memory. After the 5-week training period the nucleus basalis magnocellularis-lesioned animals received intraperitoneal injections of physostigmine sulphate (0.5 mg/kg) 30 min before each daily trial for 1 week. This treatment resulted in a significant improvement in the performance of the spatial memory task on all three measures. The ibotenate lesions reduced the activity of choline acetyltransferase by about 40% in the anterior cortex and by 15% in the posterior cortex. Hippocampal choline acetyltransferase activity was not affected, indicating that the septohippocampal cholinergic projection was spared by the lesions. The activity of glutamate decarboxylase was not affected in any of these regions. These results suggest that the cholinergic projections of the nucleus basalis magnocellularis play an important role in the acquisition of a spatial memory task.

Animals↗
PubMed1985

Electrolytic, but not 5,7-dihydroxytryptamine, lesions of the nucleus medianus raphe impair acquisition of a radial maze task.

We have previously reported that electrolytic lesions of the nucleus medianus raphe (MR) produce a deficit in the acquisition of an 8-arm radial maze task (Wirtshafter and Asin 1983). In an attempt to determine whether or not this deficit is secondary to serotonin depletion resulting from the lesion, we investigated and compared the effects of electrolytic and 5,7-dihydroxytryptamine (5,7-DHT) lesions of the MR on the acquisition of the radial maze task. Although forebrain serotonin levels after 5,7-DHT injections were reduced as much as those following electrolytic lesions, only rats with an electrolytic MR lesion were impaired on the acquisition of both a free-running maze task and on a related task, where animals were replaced into the same arm between arm choices. In contrast, 5,7-DHT-treated rats were unimpaired on both tasks compared to an ascorbate-injected control group. These findings provide further evidence that most of the profound behavioral deficits shown by rats with electrolytic MR damage are not due to serotonin depletion and are consistent with the results of other studies indicating strong similarities between the behavioral effects of limbic and MR lesions.

5,7-Dihydroxytryptamine↗
PubMed1984

Deoxyglucose uptake and choline acetyltransferase activity in cerebral cortex following lesions of the nucleus basalis magnocellularis.

The uptake of [3H]2-deoxyglucose (2-DG) into various brain regions of rats with unilateral or bilateral lesions of the nucleus basalis magnocellularis (nBM) was measured. The activity of choline acetyltransferase (ChAT) in these brain regions was also determined. Lesions of the nBM caused a significant decrease in cortical ChAT activity but had no effect on 2-DG accumulation. Pentobarbital treatment reduced 2-DG accumulation in all brain areas examined and these reductions were not influenced by the nBM lesions. The results indicate that a decrease in the cholinergic innervation of the cortex does not influence cortical glucose utilization. It appears unlikely, therefore, that the reported decrease in cortical glucose utilization in Alzheimer's disease is related to degeneration of the nBM-cortical cholinergic projection.

Alzheimer Disease↗
PubMed1984

Collateral projections of neurons of the rat globus pallidus to the striatum and substantia nigra.

Double retrograde fluorescent tracing techniques were used to evaluate the possibility that ascending and descending projections from the globus pallidus arise from divergent axon collaterals. Appropriately placed injections of different tracers (True Blue, Nuclear Yellow) into the substantia nigra and the striatum resulted in the double labelling of neurons in the globus pallidus. Conversely, simultaneous injection of two different sites within the striatum did not produce significant double labelling of globus pallidus neurons. These results indicate that at least a portion of the neurons of the globus pallidus project to both the striatum and substantia nigra, and that individual pallidal neurons do not have widespread projections to the striatum.

Animals↗
PubMed1984

Regional cerebellar choline acetyltransferase activity following peduncular lesions.

The activity of choline acetyltransferase (ChAT) in the cerebellar lobules of the rat was determined after bilateral destruction of either the superior, middle, or inferior cerebellar peduncles. A significant, 40-60% decrease in ChAT activity occurred in all subdivisions of the cerebellum (anterior lobe, posterior lobe hemisphere, posterior lobe vermis/nodulus and flocculus/paraflocculus) following bilateral inferior peduncle lesions. In contrast, bilateral lesions of the superior or middle peduncles did not result in significant reductions of enzyme activity. These findings indicate that the cholinergic afferents to the cerebellum are contained predominantly in the inferior peduncle, from which they emerge to innervate all of the gross subdivisions of the cerebellum.

Animals↗
PubMed1984

The effects of chronic lithium on behavioral and biochemical indices of dopamine receptor supersensitivity in the rat.

The effects of dietary lithium on several indices of dopamine receptor supersensitivity were examined in rats during withdrawal from chronic administration of haloperidol. Chronic haloperidol enhanced the locomotor stimulant action of d-amphetamine, and this effect was attenuated by lithium. In contrast, lithium did not affect the amphetamine response in animals that had not previously received haloperidol. Apomorphine-induced hypothermia was not influenced by the chronic haloperidol treatment. On the other hand, during withdrawal from chronic haloperidol, spontaneous locomotor activity (20 h) and apomorphine-induced stereotypy were increased, but neither of these effects was attenuated by lithium. In addition, lithium did not affect the chronic haloperidol-induced increase in 3H-spiperone binding sites in the striatum. Lithium alone had no effect on any of these measures except for causing a slight prolongation of the hypothermic effect of apomorphine. The results indicate that not all DA-receptor-mediated responses are enhanced by chronic administration of neuroleptics (e.g., apomorphine-induced hypothermia). In addition, while lithium reduces the effects of chronic haloperidol administration on d-amphetamine-induced locomotor activity, this is not because lithium prevents haloperidol-induced supersensitivity of postsynaptic DA receptors because more direct measures of this phenomenon (e.g., 3H-spiperone binding, apomorphine-induced stereotypy) are not affected by lithium.

Animals↗