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H C Fibiger

Publications and source records attributed to H C Fibiger.

At least 109 records · Page 6Linked to original sources
PubMed1990

Single cholinergic mesopontine tegmental neurons project to both the pontine reticular formation and the thalamus in the rat.

Microinjections of the cholinergic agonist carbachol into a caudal part of the pontine reticular formation of the rat induce a rapid eye movement sleep-like state. This carbachol-sensitive region of the pontine reticular formation is innervated by cholinergic neurons in the pedunculopontine and laterodorsol tegmental nuclei. The same population of cholinergic neurons also project heavily to the thalamus, where there is good evidence that acetylcholine facilitates sensory transmission and blocks rhythmic thalamocortical activity. The present study was undertaken to examine the degree to which single cholinergic neurons in the mesopontine tegmentum project to both the carbachol-sensitive region of the pontine reticular formation and the thalamus, by combining double fluorescent retrograde tracing and immunofluorescence with a monoclonal antibody to choline acetyltransferase in the rat. The results indicated that a subpopulation (5-21% ipsilaterally) of cholinergic neurons in the mesopontine tegmentum projects to both the thalamus and the carbachol-sensitive site of the pontine reticular formation, and these neurons represented the majority (45-88%) of cholinergic neurons projecting to the pontine reticular formation site. The percentage of cholinergic neurons with dual projections was higher in the pedunculopontine tegmental nucleus (6-27%) than in the laterodorsal tegmental nucleus (4-11%). In addition, mixed with cholinergic neurons in the mesopontine tegmentum, there was a small population of dually projecting neurons that did not appear to be cholinergic. Mesopontine cholinergic neurons with dual projections may simultaneously modulate neuronal activity in the pontine reticular formation and the thalamus, and thereby have the potential of concurrently regulating different aspects of rapid eye movement sleep.

Animals↗
PubMed1990

Effects of neurotensin on dopamine release and metabolism in the rat striatum and nucleus accumbens: cross-validation using in vivo voltammetry and microdialysis.

The effects of the neuropeptide neurotensin on dopamine release and metabolism in the posteromedial nucleus accumbens and anterior dorsomedial striatum of the anesthetized rat were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of dopamine efflux as evidenced by increases in the chronoamperometric signal was observed in the nucleus accumbens following intracerebroventricular injections of neurotensin. However, neurotensin failed to alter extracellular concentrations of dopamine in the striatum. The selective effects of neurotensin on mesolimbic dopamine neurons were confirmed using in vivo microdialysis. These results demonstrate that neurotensin can selectively enhance the release and metabolism of dopamine in neurons projecting from the ventral tegmental area to the nucleus accumbens.

Animals↗
PubMed1990

Intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration: biochemical and behavioral observations in a primate model of hemiparkinsonism.

Cynomolgus monkeys received intracarotid injections of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce a chronic unilateral model of parkinsonism. Extensive dopamine (DA) depletion was observed in the caudate nucleus and putamen on the side ipsilateral to the injection and this was associated with contralateral tremor, rigidity, and bradykinesia. A dose of 1.25 mg of MPTP caused ipsilateral DA loss of 99.4% in the caudate nucleus, 99.8% in the putamen, and 74.2% in the nucleus accumbens. A dose of 2.5 mg caused ipsilateral DA depletion of 99.3% in the caudate nucleus, 99.5% in putamen, and 90.1% in the nucleus accumbens. The unilateral aspect of the lesion was dose sensitive, with the 2.5-mg dose causing bilateral asymmetric DA depletion. Tissue concentrations of serotonin were not affected by the toxin. These findings confirm that intracarotid injection of MPTP may produce a useful primate model of hemiparkinsonism that can be associated with selective unilateral DA depletion when the appropriate dose of toxin is used.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Effects of transient forebrain ischemia and pargyline on extracellular concentrations of dopamine, serotonin, and their metabolites in the rat striatum as determined by in vivo microdialysis.

Striatal microdialysis was performed in rats subjected to 20 min of transient forebrain ischemia produced by occlusion of the carotid arteries during hemorrhagic hypotension. Extracellular changes of dopamine, serotonin, and their metabolites were monitored before, during, and after the ischemic insult at 10-min intervals by on-line HPLC analysis. During ischemia, extracellular dopamine increased dramatically (156 times baseline), as did 3-methoxytyramine (3-MT), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (15-25% of baseline). Upon reperfusion, dopamine was cleared from the extracellular fluid within 40 min and reached a stable level (70% of baseline). DOPAC and HVA increased (250-330%) transiently and reached their maximum 1 h following reperfusion, whereas 3-MT decreased to undetectable levels within 20 min. Although baseline levels of serotonin were not detectable, serotonin and 5-hydroxyindoleacetic acid showed a qualitatively similar temporal pattern to dopamine and its acid metabolites. Killing rats by cervical dislocation produced changes in extracellular dopamine, serotonin, and their metabolites that were almost identical to those seen during ischemia. Pargyline pretreatment 2 h before ischemia had marginal effects on the postischemic clearing of dopamine. The pargyline pretreatment, however, did increase the survival rate of rats subjected to ischemia, and this protective effect might be due to the pargyline-induced blockade of the post-ischemic monoamine oxidase-mediated increase in dopamine metabolism and the concurrent production of the potentially neurotoxic molecule, hydrogen peroxide.

Animals↗
PubMed1990

Effects of B-HT 920 on nigrostriatal and mesolimbic dopamine systems in normosensitive and supersensitive rats.

1. B-HT 920, a D2 dopamine receptor agonist, was tested for its ability to exert presynaptic actions in normosensitive rats, and for possible postsynaptic actions in rats made 'supersensitive' to apomorphine. 2. In normosensitive rats, B-HT 920 (0.01-0.3 mg kg-1, i.p.) increased dopamine concentrations and lowered metabolite levels to a similar extent in all four terminal regions examined (medial prefrontal cortex, olfactory tubercle, nucleus accumbens, caudate-putamen). Analogous effects were seen for 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid. 3. Rats which received bilateral 6-hydroxydopamine (6-OHDA) infusions into the caudate-putamen showed signs of postsynaptic dopamine receptor activation (stereotyped behaviour) in response to B-HT 920 (0.1 and 1.0 mg kg-1, i.p.) and to apomorphine (0.2 mg kg-1, s.c.). Similarly, B-HT 920 (0.1 mg kg-1) induced contralateral circling in rats that had received unilateral 6-OHDA infusions into the medial forebrain bundle; the rate of circling increased gradually over several weeks. 4. In contrast, bilateral 6-OHDA infusions into the nucleus accumbens resulted in a supersensitive (locomotor stimulant) response to a low dose of apomorphine (0.1 mg kg-1, s.c.), but not to B-HT 920 (0.01 and 0.1 mg kg-1). 5. In intact rats, withdrawal of chronic haloperidol treatment induced behavioural supersensitivity to apomorphine but not to B-HT 920.

Animals↗
PubMed1989

Basal forebrain and mesopontine tegmental projections to the reticular thalamic nucleus: an axonal collateralization and immunohistochemical study in the rat.

Using a double fluorescence retrograde labeling procedure, the present study sought to determine the degree to which basal forebrain and mesopontine tegmental neurons have axons that innervate both the reticular thalamic nucleus and the cerebral cortex. Immunofluorescence for choline acetyltransferase, somatostatin, and the calcium-binding protein parvalbumin was also performed to elucidate the neurochemical identity of basal forebrain and mesopontine tegmental inputs to the reticular thalamic nucleus. A significant portion (10-15%) of neurons in the basal forebrain and mesopontine tegmentum that were retrogradely labeled from the reticular thalamic nucleus were also found to be retrogradely labeled from the cortex. Many of these neurons stained positively for choline acetyltransferase. Of the basal forebrain neurons retrogradely labeled from the reticular thalamic nucleus, approximately 20% were found to be immunoreactive to choline acetyltransferase, whereas none was stained for somatostatin. A larger portion (up to 50%) of the basal forebrain neurons that were retrogradely labeled from the reticular thalamic nucleus were parvalbumin-immunoreactive, and some of these were also retrogradely labeled from the cortex. These results suggest that a subpopulation of cholinergic and non-cholinergic neurons in the basal forebrain and the mesopontine tegmentum may influence simultaneously the activity of neurons in the reticular thalamic nucleus and the cerebral cortex.

Animals↗
PubMed1989

Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens.

The extent to which repeated administration produces tolerance to nicotine-induced increases in dopamine transmission in the nucleus accumbens was investigated in rats. In vivo microdialysis was used to sample extracellular dopamine and metabolites after a nicotine challenge (0.35 mg/kg) in (1) naive rats, (2) acutely pretreated rats (1 prior nicotine injection), and (3) chronically pretreated rats (12-15 prior daily nicotine injections, 0.35 mg/kg per injection). Nicotine increased extracellular DA and its metabolites, and these increases were not significantly altered by either acute or chronic prior exposure to the drug. The failure to find evidence of tolerance is compatible with the hypothesis that the mesolimbic dopaminergic system is a substrate for the reinforcing properties of chronically administered nicotine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Dopaminergic neurons in the nucleus raphe dorsalis innervate the prefrontal cortex in the rat: a combined retrograde tracing and immunohistochemical study using anti-dopamine serum.

The existence of a dopaminergic projection from the nucleus raphe dorsalis (RD) to the prefrontal cortex of the rat was demonstrated by combining immunohistochemistry with retrograde tracing. Injection of horseradish peroxidase or Fluoro-gold into the medial prefrontal cortex resulted in the appearance of retrogradely labelled neurons in the RD and in other brain regions. Some of these retrogradely labelled RD neurons were shown to be immunoreactive for dopamine. These data support the view that these dopaminergic RD neurons represent an extension of the A10 cell group.

Animals↗
PubMed1989

Effects of short- and long-term haloperidol administration and withdrawal on regional brain cholecystokinin and neurotensin concentrations in the rat.

The effects of oral administration of the neuroleptic, haloperidol, on regional brain concentrations of cholecystokinin (CCK) and neurotensin were examined in the rat. Both short-term (3 weeks) and long-term (8 months) haloperidol administration increased the concentration of CCK in the substantia nigra. While short-term administration significantly increased the concentration of CCK in the ventral tegmental area and decreased the concentration of CCK in the cortex, including the medial prefrontal cortex, these effects were not observed following long-term drug administration. In contrast, long-term, but not short-term, haloperidol administration decreased the concentration of CCK in the olfactory tubercle. Withdrawal from long-term haloperidol did not alter CCK concentrations in any of the brain regions examined. Short-term haloperidol administration significantly increased the concentration of neurotensin in the caudate-putamen. Both short- and long-term administration increased the concentration of neurotensin in the nucleus accumbens, but only the increased following long-term administration reached statistical significance. Withdrawal from long-term haloperidol administration slightly decreased the concentrations of neurotensin in the caudate-putamen and nucleus accumbens. These results indicate that dopamine receptor blockade can affect both CCK- and neurotensin-containing neural systems. Furthermore, these two neuropeptides are affected differently depending upon the duration of haloperidol administration and withdrawal from this drug. The results raise the possibility that chronic administration of haloperidol may be toxic to some neurotensin-containing neurons in the basal ganglia.

Administration, Oral↗
PubMed1989

D2 dopamine receptors in the rat prefrontal cortex: characterization and alteration by stress.

D2 dopamine (DA) receptors were characterized in the medial prefrontal cortex (MPFC) of the rat by employing radioligand binding techniques which greatly reduced [3H]spiperone binding to filters, S2 serotonin receptors and spirodecanone sites. Competition studies suggested that the MPFC contains a higher proportion of D2 [high] receptors than does the striatum. The IC50 values of DA receptor antagonists in assays of MPFC tissue were correlated with their antipsychotic potencies. Stress (footshock or tailshock) increased the density of MPFC D2 dopamine receptors and decreased their affinity for [3H]spiperone. These changes were delayed in onset, being present at 27 h but not at 3 h after exposure to stress. The binding assay detected the changes when it was performed at pH 7.9 but not when the pH was reduced to 6.2. D2 dopamine receptors in the striatum and nucleus accumbens were not affected by stress.

Animals↗
PubMed1989

Neurochemical correlates of conditioned circling within localized regions of the striatum.

Two experiments were conducted to determine the effects of conditioned circling on the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) within discrete regions of the striatum (STR). The first study assessed the inherent regional distributions of these compounds with respect to the three primary axes: anterior-posterior, dorsal-ventral and medial-lateral. Concentrations of DA, DOPAC and HVA and the ratios of each metabolite to DA were found to vary across each dimension. However, the topographical distribution of each compound was unique. The results of the first experiment confirm that the STR is not a homogeneous structure. It is possible that the regional variations in dopamine metabolism underly the diverse functions which the STR is thought to modulate. The second experiment determined whether specific regions of the STR were differentially involved in the mediation of conditioned circling. DA metabolism, as estimated by metabolite concentrations and metabolite to DA ratios, was bilaterally increased within the anterior dorsomedial and dorsolateral STR, relative to noncircling, water-deprived controls. DOPAC and the corresponding ratio were enhanced selectively within the dorsomedial region, whereas HVA and its ratio to DA were increased preferentially within the dorsolateral STR. The ratio of DOPAC to DA was also enhanced within the anterior ventromedial STR. No other significant neurochemical effects were detected. These results support the hypothesis that the dorsal STR critically subserves circling. Moreover, it is possible that the medial and lateral regions of the dorsal STR are differentially involved in circling. These results also confirm previous reports of bilateral augmentation of striatal DA metabolism in association with high rates of conditioned circling.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Differential effects of cholinergic drugs on discriminative cues and self-stimulation produced by electrical stimulation of the ventral tegmental area.

Cholinergic receptors have been shown to modulate a subset of discriminative cues produced by electrical stimulation of the ventral tegmental area (VTA) in rats. The present study identified the specific cholinergic receptor type modulating these electrical brain-stimulation (EBS) cues, and assessed whether these receptors also mediated the rewarding effects of VTA EBS. The EBS cues were enhanced by the acetylcholinesterase inhibitor physostigmine and the muscarinic receptor agonists pilocarpine and RS-86, whereas the nicotinic receptor agonist nicotine had no effect. The enhancing effects of pilocarpine or RS-86 were attenuated by the muscarinic antagonist scopolamine. The EBS cues were not affected when scopolamine was injected alone, although high doses disrupted discriminated responses. Intracranial self-stimulation (ICSS) rates were depressed by physostigmine and pilocarpine and increased by nicotine and scopolamine. These results indicated a facilitatory influence of muscarinic receptors on the EBS cues, and an inhibitory role in VTA ICSS. Nicotinic receptor activation did not affect the EBS cues, but facilitated ICSS. These differential effects of cholinergic receptor activation point to a dissociation of the specific EBS cues measured in this study from the rewarding effects of VTA stimulation.

Animals↗
PubMed1989

Brainstem projecting neurons in the rat basal forebrain: neurochemical, topographical, and physiological distinctions from cortically projecting cholinergic neurons.

Magnocellular regions of the basal forebrain contain cholinergic neurons that project to the cerebral cortex. Neurons in the same basal forebrain regions innervate the brainstem. The present study investigated whether these brainstem projecting neurons are cholinergic, project also to the cortex, and share similar physiological properties as cortically projecting neurons. Data with retrograde tracing from various regions of the pons, medulla, and cortex combined with choline acetyltransferase immunofluorescence indicated that: 1) brainstem projecting neurons are usually segregated from cortically projecting and/or cholinergic neurons in the basal forebrain, 2) virtually no brainstem projecting neurons in the basal forebrain are cholinergic, and 3) only rarely do basal forebrain neurons have axon collaterals that project to both cortex and brainstem. Extracellular recordings from basal forebrain neurons confirmed the paucity of axonal collateralization and the topographic segregation between cortically and brainstem projecting basal forebrain neurons, and, in addition, showed that brainstem projecting neurons have a slower mean conduction velocity than cortically projecting neurons. These observations suggest that basal forebrain neurons projecting to the brainstem (pons, medulla) and the cortex represent separate cell populations in terms of projections, neurotransmitter content, distribution, and physiological properties.

Action Potentials↗
PubMed1989

Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis.

This study examined the acute effects of the novel antidepressant drug, bupropion, on extracellular concentrations of dopamine (DA), its metabolites, and the serotonin metabolite 5-HIAA in the striatum and nucleus accumbens using on-line microdialysis in freely moving rats. Bupropion HCl (10, 25, and 100 mg/kg intraperitoneally) increased extracellular striatal DA in a dose- and time-dependent manner; 1 mg/kg did not affect extracellular DA. The maximal response occurred within the first 20 minutes (+76%, +164%, and +443% for each dose, respectively) followed by a gradual decrease to a stable but elevated level for the next 2 hours. This neurochemical response was strongly associated with bupropion-induced stereotyped behavior during the first hour but not during the subsequent 2 hours. Bupropion decreased DOPAC concentrations, increased 5-HIAA, and had variable effects on homovanillic acid (HVA) (decreases with 10 mg/kg and increases with 25 and 100 mg/kg). The increase in extracellular DA after bupropion (25 mg/kg) was blocked by tetrodotoxin and was therefore action-potential-dependent. Bupropion produced similar neurochemical responses in the striatum and the nucleus accumbens. These results suggest that increases in DA transmission contribute to the behavioral effects of bupropion and are consistent with a role for DA in the antidepressant effects of this drug. The partial dissociation between DA release and stereotyped behavior suggests that the relationship between neurotransmitter release and behavior may be complex.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Dopamine and preparatory behavior: II. A neurochemical analysis.

Changes in the activity of dopamine-containing systems in relation to preparatory and consummatory feeding responses were investigated. In Experiment 1 rats were conditioned to associate food delivery with the presentation of a conditional stimulus (CS+). When sacrificed after exposure to the CS+ alone on a test trial, the ratio of the dopamine metabolite 3,4-dihydroxyphenylacetic acid to dopamine (DOPAC/DA ratio) was increased significantly in the nucleus accumbens. A similar trend in the ratio of homovanillic acid to dopamine (HVA/DA ratio) was also observed. Similar increases were observed in the striatum, but these were not statistically significant. In contrast, no increases were observed in the DOPAC/DA ratio or the HVA/DA ratio in either brain region when rats were permitted to consume an unsignaled meal for 7 min. These findings suggest that activation of dopamine terminals in the nucleus accumbens occurs during the anticipation of a meal, at which times the rat is engaged in preparatory feeding behaviors, but does not accompany the performance of short bouts of consummatory feeding behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Influence of inherent directional biases on neurochemical consequences of conditioned circling.

High rates of conditioned circling have been associated with a bilateral increase in striatal (STR) dopamine (DA) metabolism in rats. Experiments 1 and 2 examined the extent to which inherent directional biases, which are critical in determining the magnitude and direction of drug-induced circling, would influence the acquisition and performance of conditioned circling. No behavioral effects were evident. However, a symmetrical bilateral enhancement in DA metabolism was observed in the STR irrespective of directional biases. These results provide further evidence for the bilateral involvement of the mesotelencephalic DA projection in conditioned circling. Although conditioned circling could be established and maintained by reinforcing the response with food (Experiment 3), food itself influenced DA metabolism and therefore precluded the detection of changes in DA metabolism specific to the circling response. Specifically, DA metabolism was augmented to a similar extent in animals given noncontingently presented food.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Dopamine and preparatory behavior: III. Effects of metoclopramide and thioridazine.

The effects of metoclopramide and thioridazine on feeding behaviors of male hooded rats were investigated in 2 experiments. Metoclopramide (2.5-7.5 mg/kg) attenuated conditioned preparatory responses to a conditional stimulus signaling delivery of a meal. However, consummatory responses were affected only by the highest dose. Similar effects had previously been observed following administration of pimozide (Blackburn, Phillips, & Fibiger, 1987). Thioridazine (10-30 mg/kg) had no significant effect on any measure of feeding behavior. The different effects of the 2 drugs may be related to their preferential actions at dopamine terminals in anatomically distinct regions of the forebrain.

Animals↗