Fine structural localization of noradrenaline in vesicles of autonomic nerve endings.
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Adrenal Medulla↗
Biomedical subjects
F E Bloom
Publications and source records attributed to F E Bloom.
Fine structural localization of acetylcholinesterase in electroplaque of the electric eel.
The electroplaques composing the electric organ of the eel, Electrophorus electricus, have been utilized for the dual purpose of demonstrating the subcellular sites of acetylcholinesterase activity and as a model for comparison of the several cytochemical methods available. Fresh tissue and tissue fixed by immersion in formalin, hydroxyadipaldehyde, or glutaraldehyde was reacted with the Cu-thiocholine method, the Cu-ferrocyanide thiocholine method, or the thiolacetic acid (TAA) method using Pb, Ag, or Au as capture reagents. Controls were obtained by omission of substrate, or by addition to complete media of varying concentrations of different cholinesterase inhibitors. Reactions were run at 0-5 degrees C at a pH range of 5.0-7.1 for 0.25 to 120 min. Regardless of the capture metal, the localization obtained with TAA as substrate was identical with that observed with acetylthiocholine, the majority of precipitate being deposited on or near the external innervated surface of the plaque and within the tubulovesicular organelles opening onto the innervated surface. Both of the thiocholine methods and the Pb-TAA method showed reaction product in synaptic vesicles of the nerve endings innervating the plaque which was uninhibitable by 10(-4)M physostigmine. All methods also showed some inhibitor-sensitive deposition of reaction product in the mucoid material forming the immediate extracellular environment of the innervated surface.
Acetylcholinesterase↗
Histochemical and functional relationships of catecholamines in adrenergic nerve endings. I. Participation of granular vesicles.
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Animals↗
Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the cat to acetylcholine, norepinephrine and dopamine administered by microelectrophoresis.
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Acetylcholine↗
Levonantradol potentiates the anticonvulsant effects of diazepam and valproic acid in the kindling model of epilepsy.
The anticonvulsant effects of the cannabinoid derivative levonantradol and its ability to potentiate the anticonvulsant effects of diazepam and valproic acid were studied in rats with previously established amygdala-kindled seizures. Levonantradol administered in doses of 100 to 400 micrograms/kg did not block any components of the motor seizure. However, levonantradol did increase the latency of appearance of fully kindled seizures at the 400 micrograms/kg dose. Administration of diazepam at doses of 1 or 2 mg/kg or valproic acid at doses of 100 or 200 mg/kg produced seizure control as measured by a reduction in motor components of the seizure or a reduction in afterdischarge length or both. The anticonvulsant effects of diazepam and valproic acid were potentiated by administration of 100 microgram/kg levonantradol without apparent increases in sedation. Although the mechanism underlying this potentiation of the antiepileptic effects of valproic acid and diazepam remains unknown, levonantradol may have potential as adjunctive therapy in the treatment of complex partial seizures.
Animals↗
Adrenalectomy, dexamethasone or stress alters opioid peptides levels in rat anterior pituitary but not intermediate lobe or brain.
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Adrenalectomy↗
In vivo cellular responses to electrophoretically applied dynorphin in the rat hippocampus.
Recent immunohistochemical and radioimmunochemical observations have demonstrated a differential distribution of immunoreactive dynorphin (DYN) in rat brain. The presence of DYN immunoreactivity in a major intrinsic fiber pathway within the rat hippocampus (the mossy fiber system) has led us to evaluate the possible role of DYN and other closely related peptides in this structure. Single cell activity and hippocampal field potentials have been recorded from the CA1-CA3 cellular fields in halothane or urethane anesthetized rats. DYN, DYN1-13, DYN1-8, and alpha-neo-endorphin had an excitatory effect on most CA1-CA3 neurons encountered as has been previously observed for opiates and other opioid peptides. This response could be blocked by naloxone or by co-administration of Mg++ ion suggesting an indirect (synaptic) mechanism of excitation similar to that hypothetized for enkephalin. A significant number of CA3 neurons, however, exhibited a non-naloxone sensitive inhibitory response to DYN, related opioid peptides, and the kappa agonist WIN 35-197 (ethylketocyclazocine). Field potential analysis of CA1-CA3 neuronal responses to mossy fiber activation also indicated an excitatory, Mg++ reversible, action of iontophoretically applied DYN. These observations support our cytochemical and assay studies indicating diverse opioid systems within the rat hippocampus. In addition, these functional studies are congruent with other evidence suggesting multiple opioid mechanisms in this structure.
Animals↗
Opioid peptide identity and localization in hippocampus.
The hippocampus contains three times as much dynorphin-17 immunoreactivity (ir) as enkephalin-ir. Hippocampal mossy fibers exhibit weak enkephalin and strong dynorphin immunostaining. Intrahippocampal colchicine injections, which selectively destroy dentate granule cells, reduce enkephalin-ir and dynorphin-ir in mossy fibers. Intraventricular kainic acid, which causes degeneration of CA3-4 pyramidal cells, results in increased enkephalin immunostaining in mossy fibers. The enkephalin-ir cells and fibers of the entorhinal cortex which innervate the hippocampus and dentate gyrus do not contain dynorphin-ir.
Animals↗
Effects of chronic lithium on enkephalin systems and pain responsiveness.
We have recently undertaken an extensive examination of the effects of chronic dietary lithium treatment on levels of brain leucine-enkephalin immunoreactivity (1-enk-IR), release of endogenous 1-enk-IR from globus pallidus prisms in vitro and behavioral responsiveness to pain. Two LiCl containing diets were used. Rats on the lower strength diet attained brain Li levels of 0.40-0.55 mEq/L, while those on the higher strength diet attained levels of 0.70-1.0 mEq/L. In one series of experiments, we sought to relate alterations of K+-stimulated, Ca++-dependent release of 1-enk-IR to alterations of the content of the peptide. After 1 week on the lower strength diet, neither measure was affected in any of the brain regions examined. Following 2 or 3 weeks of feeding with the lower strength diet, 1-enk-IR levels in the globus pallidus and nucleus accumbens were elevated. However, 3 weeks of the high strength Li diet did not lead to alterations of 1-enk-IR content. In contrast, the release of 1-enk-IR was potentiated but only in subjects in which the brain lithium exceeded a threshold level. In another series of studies, we observed that hot-plate escape latency was significantly elevated in rats fed the high strength Li diet for 3 weeks. Also, the Li-treated animals had a greater morphine-induced elevation of escape latency than controls; this effect was less effectively blocked by naltrexone. These findings suggest that chronic exposure to Li leads to transiently elevated levels of 1-enk, and, when brain Li levels are greater than 0.5 mEq/L, to a potentiation of endogenous enkephalin release. The analgesia in Li-treated subjects may eventually be related to these influences of the anti-manic drug on enkephalinergic neurotransmission.
Analgesia↗
P300 assessment of early Alzheimer's disease.
The P300 (P3) event-related brain potential (ERP) was elicited in 16 demented patients presumed to be in the early stages of Alzheimer's disease and 16 normal control subjects well matched for age, sex, education and occupational level. All subjects performed a simple auditory discrimination task in which a target tone was presented randomly on 20% of the trials. P3 amplitude was smaller and peak latency longer for the Alzheimer patients compared to control subjects. A second ERP task also was administered in which the target tone occurred 50% of the time. Analysis of the target/standard tone presentation sequences indicated that the Alzheimer patient group demonstrated less amplitude difference between the target and standard sequences and longer overall latencies compared to the control group. The results suggest that the P3 ERP component from auditory stimuli can provide useful information about Alzheimer's disease during its early stages.
Acoustic Stimulation↗
Morphological and functional correlates of VIP neurons in cerebral cortex.
Vasoactive Intestinal Polypeptide (VIP) promotes the hydrolysis of 3H-glycogen newly synthesized from 3H-glucose by mouse cortical slices. This effect occurs rapidly, approximately 50% of the maximal effect being reached within one minute. The maximal effect is achieved after 5 minutes and maintained for at least 25 minutes. Furthermore the glycogenolytic effect of VIP is reversible, and pharmacologically specific. Thus several neuropeptides present in cerebral cortex such as cholecystokinin-8, somatostatin-28, somatostatin-14, met-enkephalin, leu-enkephalin, do not affect 3H-glycogen levels. VIP fragments 6-28, 16-28 and 21-28 are similarly inactive. Furthermore, among the peptides which share structural homologies with VIP, such as glucagon, secretin, PHI-27 and Gastric Inhibitory Peptide, only secretin and PHI-27 promote 3H-glycogen hydrolysis, with EC50 of 500 and 300 nM respectively, compared to an EC50 of 25 nM for VIP. Immunohistochemical observations indicate that each VIP-containing bipolar cell is identified with a unique radical cortical volume, which is generally between 15-60 micrograms in diameter and overlaps with the contiguous domains of neighbouring VIP-containing bipolar cells. Thus this set of biochemical and morphological observations support the notion that VIP neurons have the capacity to regulate the availability of energy substrates in cerebral cortex locally, within circumscribed, contiguous, radial domains.
Animals↗
Central injections of arginine vasopressin prolong extinction of active avoidance.
Behavioral and physiological effects of arginine vasopressin (AVP) were examined following intracerebroventricular (ICV) injection in the rat. ICV injections prolonged extinction of active avoidance at doses of 1.0 and 10.0 ng/rat and this effect was blocked by peripheral injection of the vasopressor antagonist of vasopressin [dPtyr(Me)AVP] at a dose of 30 micrograms/kg (SC). However, 1.0 ng of AVP ICV failed to alter systemic blood pressure and also failed to produce taste aversions in a one or two bottle test. Results suggest that central AVP has a central action independent of systemic changes in blood pressure, but that the receptor mediating this action is functionally similar to the AVP V1 (vasopressor) receptor.
Animals↗
Laminar, tangential and regional organization of the noradrenergic innervation of monkey cortex: dopamine-beta-hydroxylase immunohistochemistry.
An antiserum directed against human dopamine-beta-hydroxylase purified from pheochromocytoma tissue was employed in an immunohistochemical study of the organization of the noradrenergic innervation of monkey neocortex. A detailed description is given of the laminar pattern of noradrenergic innervation in the dorsolateral prefrontal cortex (Brodmann areas 9 and 10) and the primary somatosensory cortex of the postcentral gyrus (Brodmann areas 3,1,2). The noradrenergic innervation of these two regions is similar in the following respects: (1) fibers are present in all six layers, (2) the innervation is dense and terminal-like in layers IV and V, and (3) layer VI is characterized by fibers oriented parallel to the pial surface which follow the contours of the subcortical white matter. However, these regions differ with respect to specific laminar patterns of fiber distribution and orientation and by virtue of the fact that the primary somatosensory cortex has a very dense noradrenergic innervation, while the density of innervation in dorsolateral prefrontal cortex is low relative to the postcentral gyrus and most other neocortical areas. The laminar pattern of noradrenergic innervation in primary visual cortex differs fundamentally from both prefrontal and primary somatosensory cortices. In a separate series of experiments, dorsolateral frontal cortex lesions were used to investigate the intracortical trajectory of noradrenergic fibers. A discrete aspiration lesion confined to the grey matter of the prefrontal cortex led to a substantial loss of noradrenergic fibers in cortical regions caudal to the lesion. The decrease in density of noradrenergic innervation was particularly pronounced in the pre- and postcentral gyri. These results demonstrate that while the noradrenergic innervation of primate cortex exhibits a far greater degree of regional variation than is present in the rat cortex, the tangential intracortical trajectory that is characteristic of the lissencephalic rat brain is also a dominant feature of the noradrenergic innervation of the gyrencephalic primate brain.
Adrenergic Fibers↗
Rat blood pressure during ethanol withdrawal.
Hypertension appears to be a clinical sign of ethanol withdrawal. In an effort to see if hypertension is a general consequence of ethanol withdrawal, we have monitored blood pressure and heart rate in conscious rats during ethanol withdrawal. Sprague-Dawley rats were placed in Plexiglas chambers and exposed for 3 weeks to either ethanol vapor in air or to air alone. Blood ethanol levels in the ethanol treated group averaged 178 +/- 9 mg/dl during the last 2 weeks of ethanol exposure. Four to 18 hours prior to blood pressure measurement, rats were removed from the ethanol chambers, briefly anesthetized with halothane and implanted with an indwelling abdominal aortic cannula. Rats were either returned to the Plexiglas chambers and re-exposed to ethanol or air overnight or withdrawn from ethanol. Blood pressure and heart rate were then monitored at various periods from 5 hours to 4 days following the cessation of ethanol exposure. Analysis of variance revealed a significant decrease in blood pressure and heart rate in rats exposed to ethanol vapor as compared to controls. There was a significant negative correlation between the average blood ethanol levels, taken during ethanol exposure, and systolic blood pressure at 5 hours, 2 days and 3 days following cessation of ethanol exposure. These signs of hypotension and bradycardia indicate that hypertension is not a consequence of ethanol withdrawal in all animals.
Acute Disease↗
P300 from normals and adult children of alcoholics.
The P300 event-related brain potential (ERP) was obtained from 24 pairs of undergraduate male subjects. One member of each pair reported having a father who was alcoholic (FH+), the other reported no alcoholic family member (FH-). Pairs were matched on height, weight, academic performance, and personal drinking history. Three auditory task situations were employed which manipulated stimulus discrimination difficulty. All tasks employed 20% target and 80% standard tones randomly presented with the subjects required to move their index finger whenever a target tone was detected. No differences in P300 amplitude or latency were obtained between the groups. FH+ subjects tended to demonstrate decreased amplitudes with increased amounts of reported alcohol consumption but only for the most difficult task. The results of the present study suggest that the relationship between the P300 and the heritability for alcoholism is not yet clear and may be modulated by differences in task requirements, subject populations, and personal drinking history.
Adolescent↗
Electrophysiological action of ethanol at the cellular level.
To examine how ethanol interferes with brain function on the global levels of brain activity reflected by event-related potentials, we summarize here our recent efforts to characterize the acute cellular effects of ethanol. Four regions of the rodent brain (cerebellum, hippocampus, locus coeruleus and inferior olive) have so far been examined. The effects of acute parenteral ethanol on specific identifiable neurons within these 4 regions are highly consistent, dose-related, and spontaneously reversible. Furthermore, different patterns of response are seen in each responsive region, ranging from general increased firing in inferior olive to generally depressed synaptic transmission in hippocampus, and with more subtle effects within the cerebellum and within the locus ceruleus. This survey of consistent but differing patterns of responsiveness to ethanol at specific time points after acute exposure, suggests that the global effects of ethanol must be composed of several distinct effects both within and across many cellular systems.
Animals↗
Picrotoxinin receptor ligand blocks anti-punishment effects of alcohol.
Ethanol at low doses produces a release of punished responding in an operant rat conflict test similar to that observed for benzodiazepines and phenobarbital. It has been hypothesized that these anti-punishment effects are mediated via the GABA-benzodiazepine receptor-ionophore complex but not at the benzodiazepine binding site. In the present study isopropylbicyclophosphate (IPPO), which binds at the picrotoxinin site, reversed the release of punished responding produced by ethanol, pentobarbital and chlordiazepoxide; at low doses IPPO (less than 10 micrograms/kg) appeared to be most effective against ethanol but at higher doses (greater than 15 micrograms/kg) was also effective against pentobarbital and chlordiazepoxide. At still higher doses IPPO produced a decrease in punished and unpunished responding. These results suggest that the "anxiolytic" actions of ethanol may involve a direct action on the GABA-benzodiazepine receptor-ionophore complex and this action may underlie some of the intoxicating effects of ethanol.
Animals↗
Opponent process theory of motivation: neurobiological evidence from studies of opiate dependence.
One hypothetical model for a mechanism of drug dependence involves the development of an adaptive process that is initiated to counter the acute effects of the drug. This adaptive process persists after the drug has been cleared from the brain, leaving an opposing reaction unopposed (abstinence signs). From a motivational perspective a particularly attractive hypothesis has been that of opponent process theory (32). Here many reinforcers elicit positive affective and hedonic processes that are opposed by negative affective and hedonic processes. Thus the intense pleasure of the opiate drug "rush" or "high" would be opposed by aversive withdrawal symptoms. The present paper presents neurobiological evidence to support the opponent process concept and suggests neural circuitry that may be involved. The region of the nucleus accumbens in the forebrain of the rat has been shown to be a particularly sensitive substrate not only for the acute reinforcing properties of opiate drugs, but also for the response disruptive effects of opiate antagonists in opiate dependent rats. This region also appears to be particularly sensitive to the aversive stimulus effects of opiate antagonists using a place aversion measure in dependent rats. These results suggest that the region of the nucleus accumbens and its neural circuitry may be an important neural substrate for both the positive and negative motivational aspects of drug dependence.
Animals↗