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R F Ackermann

Publications and source records attributed to R F Ackermann.

At least 19 recordsLinked to original sources
PubMed2001

Brain mediation of Anolis social dominance displays. I. Differential basal ganglia activation.

Ritualistic displays of aggressive intent are important social signals, often obviating physically dangerous engagement. To date, however, brain regions mediating such behaviors are not established. Here we used male Anolis carolinensis together with an in vivo 14C-2-deoxyglucose method to determine patterns of brain activation during elicitation of this animal's dominance displays vs. other behaviors. By patching one eye regional brain activation in the hemisphere receiving display-evocative visual stimuli ('seeing' side) was compared to activity in the contralateral brain that did not see specific stimuli ('patched' side); this was quantitated as the ratio of seeing/patched activity for brain regions of interest. Lone males displaying dominantly to mirrors activated dorsolateral basal ganglia (BG) in the seeing, compared to the patched hemisphere; this was not seen in various non-displaying controls. Degree of dorsolateral BG activation also correlated with a measure of dominant display activity, but not with locomotion. In socially stable pairs, displaying dominants showed similar activation of dorsolateral BG, but deactivated ventromedial BG; non-dominant cagemates displaying submissively had the opposite pattern. When cohabiting peacefully without displaying, paired dominants' and subordinates' brain activity patterns were similar to each other. Thus, different BG subsystems seem involved in dominant vs. submissive display behaviors. Given similarities in both social displays and BG organization, homologous brain systems might have similar functions in members of other amniote classes, including primates.

Aggression↗
PubMed2001

Brain mediation of Anolis social dominance displays. II. Differential forebrain serotonin turnover, and effects of specific 5-HT receptor agonists.

Serotonin (5-HT) functions are associated with social dominance status in diverse species, but to date the brain regions wherein 5-HT exerts such effects are uncertain. Here, we indexed 5-HT turnover in male Anolis carolinensis as the ratio of 5-HT to its metabolite, 5-hydroxy-indol-acetic acid, and also as the accumulation of the in vivo tracer 14C-alpha-methyl-tryptophan (14C-AMT). After patching one eye, displaying dominant animals increased both measures of 5-HT turnover in the forebrain hemisphere receiving display-evocative visual stimuli, compared to control, contralateral brain, whereas both 5-HT turnover indices were decreased when animals displayed submissively. In contrast, various non-displaying controls showed forebrain symmetry on both measures. Drugs that stimulate 5-HT(2C) receptors in mammals, and have 5-HT(2C)-like binding in A. carolinensis, evoked some elements of dominant display behaviors in non-dominant anole males and also activated dorsolateral basal ganglia as seen in non-medicated dominants when they display [Baxter et al., 2001]. Thus, acute changes in forebrain 5-HT output from baseline equilibrium, acting at 5-HT(2C)-like receptors, might effect some elements of the dominant vs. submissive male anoles' territorial displays. A mechanistic model of how this might occur is offered. Given similarities in 5-HT systems, forebrain functions, and territorial display routines, similar mechanisms might have similar functions in other amniotes, including primates.

Aggression↗
PubMed2000

Mammal-like striatal functions in Anolis. II. Distribution of dopamine D(1) and D(2) receptors, and a laminar pattern of basal ganglia sub-systems.

We used in situ autoradiographic ligand binding methods to determine the occurrence and distribution of dopamine D(1) and D(2) receptor sub-types in the anole lizard, Anolis carolinensis. Both were present and exhibited pharmacological specificity characteristics similar to those described for mammals. However, unlike in mammals where in the neostriatum [outside the nucleus accumbens/olfactory tubercle complex (NA/OT)] these receptors exhibit only slight dorsolateral (D(2) high, D(1) low) to ventromedial (D(1 )high, D(2) low) gradients that co mingle extensively, in the anole striatum outside the NA/OT there was a striking laminar pattern, with little if any overlap between D(2) (high in a dorsal band) and D(1) (high ventral to the D(2) band) distributions. As D(1) receptors are related to the direct and D(2) to the indirect basal ganglia (BG) subsystems in mammals, we also determined anole striatal distributions of pre-proenkephalin mRNA, a marker for striatal efferents to the indirect BG subsystem in mammals. Here, too, there was a striking laminar pattern, with pre-proenkephalin mRNA in a band similar to that seen for D(2) receptors. The crisp neuroanatomical separation between these classic BG subsystem markers in Anolis striatum make this species attractive for the study of such systems' functions during behavior.

Animals↗
PubMed1998

Medial forebrain bundle lesions fail to structurally and functionally disconnect the ventral tegmental area from many ipsilateral forebrain nuclei: implications for the neural substrate of brain stimulation reward.

Lesions in the medial forebrain bundle rostral to a stimulating electrode have variable effects on the rewarding efficacy of self-stimulation. We attempted to account for this variability by measuring the anatomical and functional effects of electrolytic lesions at the level of the lateral hypothalamus (LH) and by correlating these effects to postlesion changes in threshold pulse frequency (pps) for self-stimulation in the ventral tegmental area (VTA). We implanted True Blue in the VTA and compared cell labeling patterns in forebrain regions of intact and lesioned animals. We also compared stimulation-induced regional [14C]deoxyglucose (DG) accumulation patterns in the forebrains of intact and lesioned animals. As expected, postlesion threshold shifts varied: threshold pps remained the same or decreased in eight animals, increased by small but significant amounts in three rats, and increased substantially in six subjects. Unexpectedly, LH lesions did not anatomically or functionally disconnect all forebrain nuclei from the VTA. Most septal and preoptic regions contained equivalent levels of True Blue label in intact and lesioned animals. In both intact and lesioned groups, VTA stimulation increased metabolic activity in the fundus of the striatum (FS), the nucleus of the diagonal band, and the medial preoptic area. On the other hand, True Blue labeling demonstrated anatomical disconnection of the accumbens, FS, substantia innominata/magnocellular preoptic nucleus (SI/MA), and bed nucleus of the stria terminalis. [14C]DG autoradiography indicated functional disconnection of the lateral preoptic area and SI/MA. Correlations between patterns of True Blue labeling or [14C]deoxyglucose accumulation and postlesion shifts in threshold pulse frequency were weak and generally negative. These direct measures of connectivity concord with the behavioral measures in suggesting a diffuse net-like connection between forebrain nuclei and the VTA.

Animals↗
PubMed1998

Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery.

Radiosurgery may provide an alternative therapy for intractable epilepsy by eliminating or modifying abnormally active pacemaker neurons in epileptic foci. In the present study, the effect of radiosurgery on rat hippocampal kindling was examined. Rats received daily hippocampal stimulus trains until they were fully kindled. They then underwent radiosurgery of the kindled focus, receiving a single-dose of 0-, 10-, or 40-Gy. The 40-Gy group demonstrated an acute decrease in seizure threshold (3-5 days). Three months after radiosurgery, the threshold for seizures increased and the duration of afterdischarges decreased in the 40-Gy radiosurgery group compared to controls. The changes to both seizure threshold and afterdischarge duration were not significant in the 10-Gy group. These data suggest that radiosurgery is an effective means of reducing the epileptogenic activity of seizure foci.

Animals↗
PubMed1996

Effects of chronic morphine pretreatment on amygdaloid kindling development, postictal seizure and suppression and benzodiazepine receptor binding in rats.

Effects of chronic morphine pretreatment on the development of amygdaloid kindling, seizure suppression and benzodiazepine (BDZ) receptor binding in rats were evaluated. The morphine-pretreated animals showed faster acquisition of seizure activity. Further evaluation of the postictal seizure suppression immediately after a fully kindled seizure demonstrated that morphine-pretreated rats had a decreased sensitivity to subsequent kindling stimulations. Twenty-four hours after the last electrical stimulation, saline-pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation site, compared to saline controls. Morphine-pretreated amygdala-kindled rats had significantly higher BDZ binding in piriform, entorhinal and sensorimotor cortices, basolateral and cortical amygdaloid nuclei, dentate gyrus, CAI-3 areas, substantia nigra pars reticulata and periaqueductal gray. The present study indicates that the previous experience with chronic morphine modifies the kindling process and that the enhanced BDZ receptor binding detected in our experiments may be involved in the enhanced postictal seizure suppression observed in these animals.

Amygdala↗
PubMed1996

Chronic and single administration of pentylenetetrazol modifies benzodiazepine receptor-binding: an autoradiographic study.

Benzodiazepine (BDZ) receptor-binding changes in the rat brain induced by pentylenetetrazol (PTZ) were investigated by in vitro autoradiography. Our experiments revealed that a single PTZ administration produced BDZ-binding decrease in cingulate, frontal, temporal, parietal and piriform cortices; caudate putamen; medial, basolateral and cortical amygdaloid nuclei; medial, ventromedial and ventroposterior thalamic nuclei; substantia nigra pars compacta and periaqueductal gray. Fully kindled rats with chronic PTZ treatment showed reduced BDZ receptor-binding in cingulate, frontal, parietal and piriform cortices; caudate putamen; medial, ventromedial and ventroposterior thalamic nuclei; and periaqueductal gray. These effects resulted from decrease in the binding capacity. Our results support that PTZ-induced chemical kindling may be associated with significant changes of the GABAergic systems and BDZ-binding from the first administration.

Animals↗
PubMed1996

Pentylenetetrazol-induced kindling: early involvement of excitatory and inhibitory systems.

Alterations in the brain of rats receiving a single non-convulsive administration pentylenetetrazol (PTZ), 30 mig/kg, i.p. (single PTZ group) were investigated and compared with those detected in fully PTZ kindled rats (chronic PTZ group). In vitro receptor autoradiography experiments showed that both single and chronic PTZ groups presented mu opioid and benzodiazepine (BDZ) receptor binding in specific brain areas. Using an antibody generated against the delta opioid receptor (DOR-1), it was found that DOR-1 like immunoreactivity was reduced in cortex and amygdala in mice following single and chronic PTZ administration. Microdialysis experiments revealed that the administration of PTZ 30 mg/kg, i.p. in freely moving rats without previous experience with the drug, induces a rise in glutamate release, detected in the first and second 10 min dialysates collected from amygdala (138% and 50%, respectively) and frontal cortex (70% and 45%, respectively) as well as aspartate in frontal cortex in the first and second PTZ-dialysates (143% and 80%, respectively). Subsequently, values returned to basal conditions. It may be speculated that decreased BDZ receptor binding results from enhanced release of GABA. On the other hand, the decrease of mu receptor binding and DOR-1 immunoreactivity observed after PTZ administration may be the result of enhanced levels of opioid peptides probably released over the kindling procedure. In conclusion, the present study indicates that PTZ-kindling is associated with an imbalance between excitatory and inhibitory systems which is apparent early in the epileptogenic process.

Amygdala↗
PubMed1995

Mapping of limbic seizure progressions utilizing the electrogenic status epilepticus model and the 14C-2-deoxyglucose method.

We have previously described a model of limbic status epilepticus in which chronic prolonged seizure states of immobile, exploratory, minor convulsive or clonic convulsive behavior are induced by intracerebral electrical stimulation; these states appear to belong to the same behavioral progression as kindled seizures. We postulated that the underlying seizure substrates, as mapped by the 14C-2-deoxyglucose method, should reflect a corresponding anatomic progression of discharge spread. Status epilepticus was induced in rat by pulsed-train current delivered for up to 90 min to one of several subcortical areas. Autoradiographs revealed that most of the observed patterns of seizure-induced metabolic activation comprised a hierarchical sequence, such that progressively more extensive patterns subsumed anatomic territories activated in less extensive patterns, thus allowing inferences as to the progression of discharge spread. In this sequence, the basolateral amygdala ipsilateral to the induction electrode was among the first structures to be activated. In successively larger activation patterns a small unilateral network related to basolateral amygdala was involved; this evolved through a transitional state to a unilateral extensive limbic pattern; which in turn was succeeded by bilateral extensive limbic activation. This hierarchical sequence culminated in a neocortical activation pattern, in which most of the forebrain was involved in intense seizure-induced activation. Seizure behaviors increased in severity in correspondence with the underlying seizure-activated anatomic substrate. In contrast, patterns of seizure activation were observed which did not fit within the early stages of the above sequence, although analysis indicates that the later stages of spread may be shared. The study of these patterns and those reported in the literature indicates that although limbic seizure networks may be anatomically distinct at their origination, further expansion is characterized by overlap; upon assumption of extensive patterns of activation the number of nuclei participating is so vast that the identity of the limbic originator is lost and common convulsive manifestations occur.

Amygdala↗
PubMed1994

Microdialysis reveals changes in extracellular opioid peptide levels in the amygdala induced by amygdaloid kindling stimulation.

Enkephalins released in basolateral nucleus of the amygdala in response to electrical stimulation were determined in amygdala kindled and nonkindled freely moving rats using microdialysis. Enkephalin release was enhanced after a single and repetitive electrical stimulation (233 and 130% above control levels, respectively) in nonkindled rats. In fully kindled rats, the extracellular enkephalin levels decreased (35% below the control levels) within the first 20 min after onset of stage V kindled seizures, reaching baseline level 40 to 60 min following the generalized seizure activity. HPLC analysis identified the majority of recovered immunoreactive material from the amygdala as Met-enkephalin. On the basis of our results it is suggested that the enhanced enkephalin release in the amygdala during the early kindling stages might have a suppressive effect which may represent a homeostatic mechanism to avoid the spread of the afterdischarge to other structures. The decreased extracellular level of enkephalin in the amygdala after stage V kindled seizures could reflect a general impairment of inhibitory mechanisms in this structure with subsequent production of seizure activity.

Amygdala↗
PubMed1994

Chronic pretreatment with naloxone modifies benzodiazepine receptor binding in amygdaloid kindled rats.

Male Sprague-Dawley rats received either naloxone (75 micrograms/h) or saline (0.5 microliter/h) s.c. for 14 days delivered with osmotic minipumps. Two days after termination of either treatment, daily amygdala kindling stimulation was applied until the animals experienced stage V kindled seizures. Benzodiazepine (BDZ) binding sites were labeled with [3H]flunitrazepam (2 nM), and changes in specific brain areas were determined by in vitro quantitative autoradiography. Twenty-four hours after the last electrical stimulation, the saline pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation compared to saline controls. Twenty-eight days after the last stage V kindled seizure, the significant alterations were no longer evident. In agreement with a previous study, we found that naloxone pretreated amygdala kindled rats showed stage V kindled seizures followed by intervals of 3-5 days in which the same electrical stimulation failed to induce any behavioral and EEG alterations. In comparison with the saline pretreated kindled and saline control groups, the naloxone pretreated kindled rats had significantly higher BDZ binding in different cortical areas, amygdala complex, hippocampus, substantia nigra and periaqueductal gray, 24 h after the last electrical stimulation. The present study indicates that previous chronic exposure to naloxone increases BDZ receptor binding in kindled rats, and suggests that this effect may be associated with the enhanced seizure suppression observed in these animals.

Amygdala↗
PubMed1993

Electrogenic status epilepticus induced from numerous limbic sites.

We have previously shown that pulsed-train electrical stimulation of the amygdala results, within 60-90 min, in status epilepticus in which one of four behavioral states is predominant: immobile, exploratory, minor convulsive and clonic convulsive. These four states form a hierarchy which appears, on electrographic and behavioral grounds, to belong to the same order of severity as limbic-kindled seizures, but not representing steady-state versions. We tested the hypothesis that it should be possible to induce prolonged seizure states from numerous limbic sites, as is the case with kindled seizures. It was found that electrogenic status epilepticus could be generated at any of 11 extra-amygdala sites, including parts of hippocampal formation, olfactory/limbic cortical areas, and caudate putamen. These four status categories could each be engendered from numerous sites without any site-specific behavioral features. Midline cortical and caudate stimulation was more prone to elicit clonic convulsive status. Such findings provide further evidence that kindled seizures and electrogenic status states belong to the same progression, and share the same underlying anatomic substrates.

Animals↗
PubMed1993

Characterization of mu opioid receptor binding during amygdala kindling in rats and effects of chronic naloxone pretreatment: an autoradiographic study.

Using in vitro autoradiography, mu receptor binding in rat brain was characterized at different amygdala kindling stages and in amygdaloid kindled animals pretreated chronically with naloxone. Male Sprague-Dawley rats implanted with bipolar electrodes in the right amygdala received one of the following pretreatments s.c. for 14 days via osmotic minipumps: normal saline solution, 0.5 microliters/h, or naloxone HCl, 75 micrograms/h. Two days after treatments were accomplished animals were stimulated daily. Our data showed different patterns of mu receptor binding during the normal kindling process: during stage II-III, pronounced binding increase was detected in cingulate, temporal and entorhinal cortices, anterior amygdala, caudate putamen, thalamic nuclei, ventrolateral and dorsolateral portions of central gray, substantia nigra pars compacta and pars reticulata. Twenty-four hours after the last stage V kindled seizure, enhanced binding was observed in cingulate and frontoparietal cortices, anterior amygdala, caudate putamen and ventromedial thalamic nucleus. Twenty-eight days after the last stage V kindled seizure, binding augmentation was noticed in cingulate and frontoparietal cortices, whereas decreased binding was detected in amygdala complex, substantia nigra pars reticulata, piriform, perirhinal, parietal, temporal and entorhinal cortices. Mu receptor binding in kindled rats chronically pretreated with naloxone was significantly higher in several structures when compared with control and normal kindled groups. Our data indicate different regional selective patterns of mu receptor binding during amygdala kindling which may depend on epileptogenesis and long-term changes induced by this process. In addition, even higher mu receptor binding results from chronic naloxone administration prior to kindling.

Amygdala↗
PubMed1990

Evaluation of radiolabeled acetate and fluoroacetate as potential tracers of cerebral oxidative metabolism.

We investigated the potential use of radiolabeled acetate (ACE) and fluoroacetate (FACE) as tracers of cerebral oxidative (Krebs cycle) metabolism. The rates of cerebral accumulation of 14C-labeled FACE and ACE were compared with glucose metabolic rates measured simultaneously with 18F-fluorodeoxyglucose (FDG) in awake rats using dual-tracer quantitative digital autoradiography. Both FACE and ACE crossed the blood-brain barrier at approximately the same rate as glucose. Metabolism of FACE by the brain, however, was extremely slow; metabolites were practically undetectable above background precursor levels through 60 min. Metabolic uptake of ACE by the brain was significant by 10 min; its rate of accumulation averaged approximately 70-80% of the glucose rate. While the metabolic images of ACE were similar to those of FDG, variations in the uptake patterns of FDG and ACE occurred in some structures, perhaps related to regional variations in glucose versus oxygen metabolism.

Acetates↗
PubMed1990

Ultra-high performance, solid-state, autoradiographic image digitization and analysis system.

We developed a Macintosh II-based, charge-coupled device (CCD), image digitization and analysis system for high-speed, high-resolution quantification of autoradiographic image data. A linear CCD array with 3,500 elements was attached to a precision drive assembly and mounted behind a high-uniformity lens. The drive assembly was used to sweep the array perpendicularly to its axis so that an entire 20 x 25-cm autoradiographic image-containing film could be digitized into 256 gray levels at 50-microns resolution in less than 30 sec. The scanner was interfaced to a Macintosh II computer through a specially constructed NuBus circuit board and software was developed for autoradiographic data analysis. The system was evaluated by scanning individual films multiple times, then measuring the variability of the digital data between the different scans. Image data were found to be virtually noise free. The coefficient of variation averaged less than 1%, a value significantly exceeding the accuracy of both high-speed, low-resolution, video camera (VC) systems and low-speed, high-resolution, rotating drum densitometers (RDD). Thus, the CCD scanner-Macintosh computer analysis system offers the advantage over VC systems of the ability to digitize entire films containing many autoradiograms, but with much greater speed and accuracy than achievable with RDD scanners.

Animals↗
PubMed1990

Long-term increase of glutamate decarboxylase mRNA in a rat model of temporal lobe epilepsy.

Behavioral changes following injury, neural degeneration, and aging partly reflect the synaptic plasticity of the nervous system. Such long-term plastic changes are likely to depend on alterations in the production of proteins involved in synaptic structures and neurotransmission. We have studied the regulation of the mRNA encoding one such protein, glutamate decarboxylase (GAD), the rate limiting enzyme of GABA synthesis, after a unilateral lesion in the hippocampus that leads to increased seizure susceptibility. Quantitative in situ hybridization reveals a long-term increase in GAD mRNA in several bilateral structures, as well as in specific neurons in the ipsilateral dentate gyrus. Our data do not support the often stated hypothesis that seizure susceptibility depends on the malfunction of GABA neurons.

Animals↗