bluuebunny/crossref_metadata_2025 huggingface dataset:
On the hippocampus and learned conditional responding: Effects of aspiration versus ibotenate lesions
Authors: Jarrard Leonard E. , Davidson T. L.
Published: January 2005

To study the possible involvement of the hippocampus in learned conditional responding, rats with aspiration lesions of the hippocampus and others that had the hippocampus removed with ibotenic acid were trained on concurrent Pavlovian conditional and nonconditional discriminations. In agreement with the results reported by Ross et al. (1984), animals that had the hippocampus removed with aspiration were unable to learn the conditional discrimination, but learned the simple nonconditional discrimination without difficulty. In contrast, rats that had the hippocampus removed with ibotenic acid did not differ from controls in learning either discrimination. Furthermore, transfer test results were consistent with the hypothesis that ibotenatelesioned rats performed conditional operations to solve the conditional discrimination problem. Histological analysis indicated that the ibotenate lesions resulted in the removal of the hippocampus and dentate gyrus with minimal involvement of other structures. In aspiration hippocampal animals there was less overall damage to the hippocampus, but there was also extensive damage to the axons passing in alveus and fimbria, together with bilateral loss of cells in the subicular complex, the cingulate gyrus, and the cortex. Since rats with ibotenate lesions had more complete removal of the hippocampus, yet learned both discriminations, the impaired conditional responding found in aspiration hippocampals must be due to extrahippocampal damage.
Firing of human hippocampal units in relation to voluntary movements
Authors: Halgren Eric
Published: January 2005

During certain movements (termed “type I,” “instrumental,” or “voluntary”), the rodent hippocampal EEG is domicated by regular 7–10 Hz waves. This “theta rhythm” is accompanied by increased firing of hippocampal interneurons and dentate gyrus granule cells. No obvious theta rhythm is present in comparable situations in humans or other primates. However, a widespread scalp negativity (the “readiness potential”) starts approximately 1 second before spontaneous key presses at long intervals. The readiness potential has been recorded in the monkey hippocampus. In this study, action potentials were recorded in the human hippocampus in relation to various movements. During a broadly ranging interview including various movements and memory tests, hippocampal units were found that fired during movements of the tongue and/or hands. Only movements that required a high degree of effort were effective. Other hippocampal units appeared to be correlated with either the transitions between tasks or the interruptions within tasks. In a second experiment, hippocampal units were found to change their firing in the seconds preceding spontaneous key presses. These data indicate that, like the rodent hippocampus, human hippocampal neuronal activity is strongly influenced by movement.
Learning‐related patterns of CA1 spike trains parallel stimulation parameters optimal for inducing hippocampal long‐term potentiation
Authors: Otto Tim , Eichenbaum Howard , Wible Cynthia G. , Wiener Sidney I.
Published: January 2005

Recent studies have revealed 3 stimulation parameters that together comprise the temporal pattern of neuronal activation optimal for the induction of hippocampal LTP: high‐frequency bursts, activity 100–200 ms prior to a burst, and burst delivery in phase with the ongoing hippocampal theta rhythm. The present paper reports that these 3 aspects of patterned neural activity, collectively referred to as “theta‐bursting,” are characteristic of the spike trains of CA1 pyramidal cells in rats during the sampling and analysis of learning cues in an odor discrimination task and during performances of a spatial memory task. In contrast, theta‐bursting occurs relatively infrequently during behavioral events less directly related to task‐relevant mnemonic processing. These findings suggest that the optimal conditions for the induction of LTP occur naturally in behaving animals, time‐locked to behavioral events critical to learning.
Extrinsic modulation of theta field activity in the entorhinal cortex of the anesthetized rat
Authors: Dickson Clayton T. , Trepel Christopher , Bland Brian H.
Published: January 2005

Field recordings of the entorhinal cortex (EC) were studied and compared to those recorded concomitantly in the dentate region of the hippocampal formation (HPC) in the urethane anesthetized rat. The EC, like the HPC, showed two main variations of spontaneous field activity: a desynchronized, large amplitude irregular activity and a synchronized, rhythmic, slow frequency field activity (RSA or theta). Corroborating previous research, a phase reversal was seen across layer II of the EC and when recorded superficial to this layer, EC theta was phase‐locked to that recorded from the HPC (dentate). Entorhinal cortex (and HPC) theta could be evoked by the application of moderate tail pinches (sensory stimulation), by pharmacological treatments enhancing cholinergic transmission, and by electrical stimulation of the posterior hypothalamus. Spectral analysis revealed that in all cases, theta was produced coherently across the two limbic structures. Entorhinal cortex (and HPC) production of theta could be abolished by pharmacological treatments disrupting cholinergic transmission, and by reversible procaine inactivation of the medial septal region. Therefore, it was concluded that limbic theta is modulated spontaneously, and with sensory and hypothalamic stimulation through the activity of cells in the medial septal region via muscarinic neurotransmission. It was also hypothesized that the activation of cells in the posterior hypothalamus linearly codes the frequency, and to a lesser extent the power, of EC and HPC theta. Given these findings and the coincidence and coherence of the occurrence of theta across the EC and HPC, it was postulated that it occurs via a parallel mechanism in the two areas.
Transient decrease in calbindin immunoreactivity of the rat fascia dentata granule cells after repeated electroconvulsive shocks
Authors: Tønder Niels , Kragh Jørn , Bolwig Tom , Zimmer Jens
Published: January 2005

Changes in hippocampal calbindin immunoreactivity were investigated after repeated electroconvulsive shocks. Adult rats were subjected to 10, 20, or 36 electroconvulsive shocks (50 mA, 0.5 seconds), given as on shock per day, 5 days a week. The rats were sacrificed and processed for calbindin immunohistochemistry 1, 2, and 30 days after the last electroconvulsive shock. In the rats receiving 10 or 20 electroconvulsive shocks, a selective reduction of the calbindin immunoreactivity of the dentate granule cell bodies, dendrites, and mossy fibers was noted 1 and 2 days after the last electroconvulsive shock. After 36 electroconvulsive shocks there was an almost complete loss of calbindin immunoreactivity from the granule cell bodies and dendrites, and the calbindin immunoreactivity of the mossy fibers was markedly reduced. Thirty days after the last of 36 electroconvulsive shocks, the calbindin immunoreactivity was back to normal. Besides demonstrating pronounced changes associated with repeated electroconvulsive shocks, the results confirm the transient nature of these changes.
Contribution of synapses in the medial supramammillary nucleus to the frequency of hippocampal theta rhythm in freely moving rats
Authors: McNaughton Neil , Logan Barbara , Panickar Kiran S. , Kirk Ian J. , Pan Wei‐Xing , Brown Nicola T. , Heenan Anna
Published: January 2005

We have previously shown that in urethane‐anesthetized rats the frequncy of rhythmical slow activity in the hippocampus (“theta”) is controlled by the medial supramammillary nucleus (SuM). In particular, injections of procaine into SuM in urethane‐anesthetized animals reduce the frequency of theta. However, it has been reported that, in freely moving animals, lesions of SuM do not affect theta. The present experiments were designed to resolve this anomaly. Injections of procaine or chlordiazepoxide into SuM in urethane‐anesthetized animals reduced the frequency of theta elicited by reticular stimulation. Mapping showed that procaine injections in freely moving animals were effective in the same locations as under urethane anesthesia. Injections of chlordiazepoxide were effective in a more restricted area than procaine, consistent with an action on synapses in SuM and sparing fibers afferent to SuM. Analysis of the functional spread indicated an effective radius of diffusion of the drugs of 500μm. With optimal placements, this implied an action on at least 80% of SuM. However, in contrast to the results under urethane, the maximal frequency reductions obtained were less than 50% of the theoretical maximum. In a number of animals receiving repeated injections into SuM, lesions developed which encompassed the whole of SuM. As previously reported, theta was largely intact in SuM‐lesioned animals. However, the frequency of theta produced by reticular stimulation was reduced after lesion by approximately the same amount as by procaine injections before lesion. These results suggest that in freely moving animals SuM is only one of two or more nuclei which jointly control the frequency of reticular‐elicited theta. © 1995 Wiley‐Liss, Inc.
Selective damage to the hippocampal region blocks long‐term retention of a natural and nonspatial stimulus‐stimulus association
Authors: Bunsey Michael , Eichenbaum Howard
Published: January 2005

Normal rats rapidly acquire and remember associations between nonspatial stimuli as expressed in the social transmission of food preferences. In the present study, rats with selective neurotoxic lesions including all subdivisions of the hippocampal region (hippocampus proper, dentate gyrus, and subiculum) normally acquired and briefly retained the food odor association as demonstrated by intact memory immediately after social training. However, long‐term memory in these animals was severly impaired in contrast to strong 24‐h retention by intact rats. More selective lesions to the hippocampus proper plus dentate gyrus alone, or the subiculum alone had no effect on memory at either test interval. These finding indicate that the hippocampal region is required for long‐term retention of a nonspatial form of natural memory. © 1995 Wiley‐Liss, Inc.
Hypothalamic tissue stimulates hippocampal pyramidal neuron survival during development: Evidence from intraocular double transplants
Authors: Curtis M. , Bergman H. , Price M. L. , Srivastava N. , Granholm A.‐Ch. E.
Published: January 2005

The present study was undertaken to evaluate innervation and possible growth promotion by posterior hypothalamic tissue on different areas that are, or are not, interactive with this brain region during development. Posterolateral hypothalamus was dissected from embryonic day 17 rat fetuses, and inserted into the anterior chamber of the eye of adult rat hosts. Two weeks postgrafting, a second transplant consisting of either fetal hippocampal, cerebellar, or lung tissue was placed adjacent to the first graft. Growth of the intraocular double transplants was monitored weekly by measurements through the cornea. Fetal hippocampal tissue grew significantly larger when placed together with a hypothalamic graft, as compared to single hippocampal transplants. Cerebellar or lung tissue growth was not stimulated by a hypothalamic cograft. Pyramidal neuron cell counts demonstrated a significantly higher final number of these neurons in growth‐stimulated hippocampal grafts, as compared to non‐stimulated single hippocampal grafts. Immunohistochemistry with antibodies directed against histamine or histidine decarboxylase revealed that hippocampal transplants received the most dense histaminergic innervation. Cerebellar transplants contained occasional histaminergic neurites, and lung tissue never exhibited any histaminergic innervation from the adjacent hypothalamic graft. Taken together, these results demonstrate a growth‐promoting effect of posterior hypothalamic tissue on developing hippocampal tissue, as well as target specificity of histaminergic innervation patterns. © 1995 Wiley‐Liss, Inc.
Cognitive functioning in a hypnotic drug trial
Authors: Wheatley David
Published: January 2005

In a 2 week comparative trial between lormetazepam (LMA) and temazepam (TEM) in 162 insomniac patients, Critical Flicker Fusion Threshhold (CFFT) and Digit Symbol Substitution (DSS) tests were performed, pre‐treatment and at days 7 and 14. With neither drug was there any difference in CFFT, but highly significant improvement in DSS (p < 0.001). Patients completed daily visual analogue scales concerned with various sleep parameters and daytime effects. Sleep was significantly improved with both drugs from day 1 onwards, as were daytime general wellbeing and alertness. There was significant improvement in daytime balance and coordination in the LMA group (p < 0·001 by day 14) but not in the TEM group. Daytime anxiety improved significantly in both groups, but on day 14 this improvement was still significant in the LMA group (p < 0·001) but not in the TEM group. The incidence of daytime fatigue (p < 0·001), drowsiness (p < 0·02) and headache (p < 0·001) were significantly reduced with LMA and daytime fatigue (p < 0·01) and headache (p < 0·001) with TEM, but with no significant between group differences. The severity of daytime fatigue was significantly less with LMA than with TEM (p < 0·05).
Kinins in the brain
Authors: Figueroa C. D. , Worthy K. , Bhoola K. D.
Published: January 2005

We have reviewed the literature on the kallikrein‐‐kinin system in the brain. Highlighted are some of the actions and possible clinical relevance in pain perception, vasogenic brain oedema and Alzheimer's disease.
Lithium neurotoxicity—the reliability of serum lithium measurements
Authors: Amdisen A.
Published: January 2005

Some of the case reports describing presumed lithium/neuroleptic interactions are considered. Lithium toxicity is proposed as a possible mechanism. The paucity of data provided on the 12‐hour serum lithium levels should be noted. Most case reports do not specify the time interval between the last lithium dose and the time of venesection. Also, inadequate consideration seems to have been given to individual pharmacokinetic variability and demonstrates an apparent lack of awareness of the physiological time‐course of sub‐acute lithium toxicity.
Is there a therapeutic window for plasma concentration of mianserin plus desmethylmianserin?
Authors: Otani Koichi , Kaneko Sunao , Sasa Hiroshi , Kondo Tsuyoshi , Fukushima Yutaka
Published: January 2005

The relationship between clinical effects and plasma concentrations of mianserin and desmethylmianserin was studied in 29 cases of major depression during 3 weeks of mianserin treatment. The daily dose of mianserin was 30 mg in 27 cases and 20 mg in two cases. There was a significant U‐shaped relationship between the final Montgomery Åsberg Depression Rating Scale (MADRS) score and the steady‐state plasma concentration of mianserin (p<0·05) or desmethylmianserin (p<0·05). A much stronger relationship was observed for mianserin plus desmethylmianserin (p<0·001). A theoretical therapeutic window (where a final MADRS score was expected to be 10 or less) was 71–128 nmol/1 for mianserin, 34–61 nmol/1 for desmethylmianserin, and 101–183 nmol/1 for mianserin plus desmethylmianserin. The proportion of responders was significantly higher inside than outside the window for mianserin plus desmethylmianserin (p=0·0033), but not for mianserin (p=0·063) or for desmethylmianserin (p=0·077). The occurrence of subjective side‐effects was not dependent on the plasma concentrations of these compounds. The present study suggests that desmethylmianserin contributes substantially to the overall antidepressant effects of mianserin treatment, and that the therapeutic response is most dependent on the combined plasma concentration of mianserin and desmethylmianserin, with an optimal therapeutic response occurring in the intermediate range.
Disposition of haloperidol and reduced haloperidol plasma levels after single dose haloperidol decanoate administration
Authors: Chang Wen‐Ho , Juang Dong‐Juiing , Lin Shih‐Ku , Huang Jin‐Ding , Lam Yw Francis , Jann Michael W. , Chien Ching‐Piao
Published: January 2005

A single dose of haloperidol decanoate 100 mg was administered to 15 schizophrenic patients. Blood samples were obtained prior to injection, 1 h, 3 h, 6 h, 8 h, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, one week, two weeks, three weeks and four weeks post‐injection. Haloperidol and its reduced metabolite, reduced haloperidol, plasma levels were assayed by HPLC with electrochemical detection. The pharmacokinetic parameters of haloperidol were determined. The mean time of maximal (Tmax) plasma levels for haloperidol was 5·73 ± 0·80 days. The haloperidol plasma levels showed a biexponential decline with an elimination half‐life of 15·78 ± 5·90 days. Reduced haloperidol was rapidly formed from the haloperidol. The Tmax of reduced haloperidol was 7·00 ± 2·35 days. The mean ratio reduced haloperidol/haloperidol was 0·155 ± 0·111. Since the Tmax occurs at approximately six days, a weekly loading dose of haloperidol decanoate is feasible during the transition from oral to depot therapy.
Cerebral ventricular enlargement and neuroleptic response in chronic schizophrenia: Preliminary findings with risperidone
Authors: Bersani Giuseppe , Venturi Piero , Tanfani Giuseppe , Pancheri Paolo
Published: January 2005

In this pilot clinical study the aim was to investigate whether the clinical response to a chronic treatment with risperidone was related to brain morphology. We evaluated the relationship between Ventricular–Brain Ratio (VBR), and clinical response to risperidone, as assessed through the Positive and Negative Syndrome Scale (PANSS). Eighteen chronic schizophrenics (DSM III‐R diagnostic criteria) were subjected to a computerized tomographic scan. For the total PANSS and each PANSS subscale (Positive, Negative and General Psychopathology) the percentage change between baseline rating and the score measured at 28, 56 days and 1 year of treatment was calculated. VBR was positively related to the percentage decrement of the total PANSS score, the Negative subscale score and the General Psychopathology subscale score as measured at one year of continuous treatment with risperidone. There was no significant differences between completers (subjects who complete the therapy with risperidone) (N = 8) and noncompleters (N = 10) when baseline clinical characteristcs were compared. VBR was not significantly different in the two subgroups.
Diet and gender moderate clozapine‐related weight gain
Authors: Heimberg Carolyn , Gallacher Fiona , Gur Ruben C. , Gur Raquel E.
Published: January 2005

This study examined patients with schizophrenic disorders treated with clozapine in a state hospital setting. Gender and diet affected weight gain over a six‐month period. Pre‐treatment weight status also related to eventual weight gain. There were no significant effects of dosage. Weight gain was most pronounced in non‐dieting women. This has implications for management of patients on clozapine.
The effect of trimethadione on brain energy metabolism and EEG activity of the conscious rat exposed to HPO
Authors: Mayevsky Avraham
Published: January 2005

The use of trimethadione (TMO) as a protector in hyperbaric oxygen toxicity in the conscious rat has been examined in detail. The oxidation‐reduction state of pyridine nucleotides was measured simultaneously with the EEG activity from the surface of the brain cortex. From the data obtained, a few parameters were calculated. The results show that in TMO‐treated animals the time to the onset of convulsions, the time to the onset of NADH oxidation‐reduction cycles, and the survival time were significantly longer than in the control group. The effect of TMO on the EEG shows that the tonic phase of the convulsive activity was almost completely abolished.
Nicotine‐induced reflex depression of α motoneuron activity in the absence of fusimotor‐spindle feedback
Authors: Ginzel K. H. , Estavillo J. , Eldred E.
Published: January 2005

The effects of nicotine on the stretch reflex and on electrically induced monosynaptic and cutaneous polysynaptic reflex responses at a lumbosacral level were studied in lightly anesthetized (chloralose‐urethane) cats in which the regional fusimotor‐spindle loops had been interrupted by ventral rhizotomy. Doses of 15–40 μg/kg injected into the superior vena cava or the right atrium produced depression of the reflex responses in extensor and flexor α motoneurons after latent periods of 1–3 sec, while γ activity was initially accelerated. The early phase of this α depression was abolished by bilateral vagotomy. Sebacylcholine (a nicotinic agent) and acetylcholine also caused depression of evoked α activity in the absence of spindle feedback. It is concluded that nicotine activates a viscerosomatic reflex by exciting sensory receptors in the cardiopulmonary region and that α motor depression results independent of the changes in γ activity. However, α depression with delayed onset can still be elicited by nicotine after vagotomy and Renshaw blockade, and this effect is also duplicated by sebacylcholine and aboilshed by hexamethonium. In the doses used, spindle or skin afferents were not excited by nicotine. Thus, two more mechanisms are described by which nicotine can depress α activity. Both are reflex in nature, one implicating vagal, the other nonvagal peripheral receptors.
Tryptophan metabolism and the occurrence of amino acids and serotonin in the leech (Hirudo medicinalis) nervous system
Authors: Stenzel Karin , Neuhoff Volker
Published: January 2005

The occurrence and distribution of serotonin (5‐HT) and amino acids along the central nerve chain of the leech, Hirudo medicinalis, was analyzed using dansylchloride in order to obtain information on the functional roles of amines and amino acids. There was no statistical variation in the occurrence of most of the amino acids or serotonin in the different parts of the dorsal nerve chain of the leech. A variation in the serotonin content was found during the year with the highest level occurring in winter. Leech ganglia also accumulated 3H‐tryptophan and metabolized part of it to form 5‐HTP, 5‐HT, and 5‐HIAA. The resutls are discussed from the point of view of 5‐HT being a transmitter substance.
The chronic and acute effects of ethanol on adenosine triphosphatase activity in cultured astroblast and neuroblastoma cells
Authors: Syapin P. J. , Stefanovic V. , Mandel P. , Noble E. P.
Published: January 2005

Mg2+ATPase and (Na+K+)ATPase activities were measured in clonal line NN hamster astroblasts and in clonal lines M1 and N1E‐115 mouse neuroblastoma cells after the cells had been subjected to the acute and chronic actions of 100 mM ethanol. Exposure of the astroblasts to ethanol for periods as long as 68 days produced an increase in total cellular Mg2+ ATPase activity, as measured in cell homogenates; however, activity reverted to control levels upon withdrawal of ethanol. Chronic exposure of clonal line N1E‐115 neuroblastoma cells to ethanol produced an increase in Mg2+ATPase and (Na+K+)ATPase activities. In contrast, the activities of both ATPases of clonal line M1 neuroblasts were unaffected by chronic exposure to ethanol. Acute exposure of cell homogenates to 100 mM ethanol inhibited Mg2+ ATPase and (Na+K+)ATPase of astroblasts but not that of neuroblastoma cells. These findings suggest that neural cells in culture may serve as useful models for studying the effects of ethanol on specific cell types.
Production of the weanling rat dorsomedial hypothalamic syndrome by cathodal electrolytic lesion current
Authors: Bernardis Lee L. , Goldman Jack K.
Published: January 2005

Weanling male Sprague‐Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic area by means of a direct cathodal current. Sham‐operated rats served as controls. Ponderal and linear growth, obesity index, food intake, and several indices of intermediary metabolims of adipose tissue and muscle were measured. Cathodal lesions, as did anodal lesions reported on previously, resulted in retardation of body weight, length, and food intake, while the obesity index remained in the normal range. Similarly, the metabolic data in adipose tissue and muscle are comparable to those from experiments in which dorsomedial lesions were placed by anodal current: incorporation of glucose into CO2, lipid, and glycogen of muscle tissue (diaphragm) were similar in DMN‐lesioned rats and controls. The difference between anodal and cathodal lesions in this hypothalamic syndrome is a delay in the onset of hypophagia until about 30 days after the hypothalamic operation. The data support the concept that lesions in the hypothalamus, in general, exert their effect by destruction of neuronal assemblies, i.e., nerve cells and/or fiber tracts passing through the lesioned area.
Comparison of light‐microscopic methods for visualizing horseradish peroxidase granules in stained and unstained tissue
Authors: Anderson Kenneth V. , Rosing Howard S.
Published: January 2005

This study was directed toward a comparison of the effectiveness of three different light‐microscopical methods for identifying and studying the features of cells that contain horseradish peroxidase (HRP) granules. The cells studied were located in the trigeminal ganglia and were labeled after the injection of HRP solutions into single, maxillary, canine teeth. The tissue was examined with light field, dark field, and differential interference optics systems. The results indicated that differential interference optics were especially useful in revealing the presence of intracellular HRP granules in both unstained and stained tissue, particularly when cells only contained small amounts of HRP. It was also noted that a wide variety of quantitative analyses could be performed with differential interference optics, even when using unstained tissue.
Biochemical markers of ethanol effects on brain
Authors: Klemm W. R. , Engen R. L.
Published: January 2005

Because sialic acid is a potential biochemical marker of membrane development or alteration, we compared acute and chronic ethanol effects on sialic acid. Experiments were conducted with 50 adult male Wistar rats (∽400 gm), housed in groups of five. Rats drank ad libitum a vitamin‐fortified diet (Nutrament) that was adulterated with ethanol; ethanol intake averaged for each rat 10–18 gm/kg/day. Controls were fed an equal total volume, made isocaloric with sucrose. Rats were sacrificed weekly for four weeks, and an acute challenge dose of ethanol (2 gm/kg, intraperitoneally) was given 45 minutes before sacrifice of both control and ethanol‐consuming rats. Some controls were challenged only with saline. We replicated our earlier findings of regional differences in sialic acid and in cerebellar deoxyribose (measured as a necessary adjunct in the autoanalyzer modification of the Warren‐Delmotte methods).

In the saline‐challenged controls, levels of both compounds were higher at four weeks than after one week. Similar increases occurred also in the chronic ethanol‐consuming group, but not in the ethanol‐challenged controls, which had significantly lower values. Results in saline‐challenged controls suggest that the chronic treatment either 1) created a tolerance which protected cells from damage by the challenge dose of ethanol, or 2) killed neurons, thus promoting proliferation of glial cells.
Acutely administered ethanol decreases whole‐brain sialic acid and cerebellar 2‐deoxyribose
Authors: Klemm W. R. , Engen R. L.
Published: January 2005

As a follow‐up to a previous study that suggested that acutely administered ethanol could decrease steady‐state brain levels of sialic acid (SA), we evaluated the time course of the ethanol effect and tested the influence of route of administration and sex.

Compared to the control treatments, ethanol (2 gm/kg) significantly decreased brain SA in each of the four brain regions that were tested. The decrease was evident by 30 minutes after ethanol administration, but peak effect was reached at about 1–2 hours. The decrease occurred with either injection or self‐administration, but the greatest decrease occurred in the self‐administration group. The SA‐induced decrease was greatest in females.

An ancillary part of the study included measurement of brain levels of 2‐deoxyribose (DR). Ethanol given by either route of administration caused a preferential decrease in DR levels in the cerebellum.

Lesser, but statistically significant, decreases in SA and DR occurred in controls, suggesting that these chemicals are sensitive to subtle environmental contingencies associated with the experimental procedures.
Glycerol oxidation in rat brain: Subcellular localization and kinetic characteristics
Authors: Tildon J. Tyson , Roeder Lois M.
Published: January 2005

The oxidation of [1,3‐14C]glycerol to 14CO was measured in slices, whole homogenates, and subcellular fractions of rat brain. In all of these tissue preparations, the Lineweaver‐Burk plots of glycerol oxidation were biphasic, yielding two apparent Km and V values. Similar kinetic characteristics were obtained with brain homogenates from guinea pig, mouse, rabbit, monkey, and pig. In other tissues of the rat, including heart, kidney, liver, and skeletal muscle, the Lineweaver‐Burk plots for glycerol oxidation were not biphasic but were linear. Heating the brain homogenates for five minutes at 5°C caused a 50% decrease in the rate of oxidation of glycerol without a change in the biphasic double reciprocal plot. The addition of purified glycerol kinase (EC 2.7.1.30) to the homogenate caused an increase in the rate of oxidation and resulted in a linear Lineweaver‐Burk plot. Brain mitochondria were prepared by two different methods, both of which yielded an enrichment of glycerol oxidation. In contrast, the rate of glucose oxidation was higher in homogenates than in mitochondria, and glucose competed with glycerol as substrate only extramitochondrially. The effects of various metabolic inhibitors suggested the participation of intact, coupled mitochondria, of glycolytic enzymes, and of electron transport in the oxidation of glycerol. The data support the primary localization of glycerol oxidation in nonsynaptic mitochondria in brain and the presence in that organelle of enzymes of the Embden‐Meyerhoff pathway or an as yet unidentified system for oxidizing this compound.
GABA uptake in astrocytes in primary cultures: Coupling with two sodium ions
Authors: Larsson O. M. , Hertz L. , Schousboe A.
Published: January 2005

The influence of sodium ions on GABA uptake into astrocytes in primary cultures has been investigated performing kinetic analysis of GABA uptake at different sodium concentrations in the range 16 to 151 mM. These investigations reveal that sodium affects both the Km and the Vmax of the saturable component of the astroglial GABA uptake. Uptake rates as a function of the sodium concentration at high GABA concentrations (≥ 50 μM) were clearly sigmoid whereas at lower GABA concentrations this sigmoid shape was not obvious. Accordingly, Hill plots of the sodium dependency at high GABA concentrations exhibited straight lines with slopes of 2.0 to 2.5, suggesting that the coupling ratio between sodium and GABA is at least two. Corresponding Hill plots at lower GABA concentrations exhibited slopes of 1.6 to 1.8. Moreover, plots of 1/v versus 1/Na2 gave better fits to straight lines than plots of 1/v versus 1/Na which were curvilinear upward. Again, this curvilinearity was more pronounced at high GABA concentrations than at low GABA concentrations. From these results it is concluded that GABA uptake into astrocytes in primary cultures requires the binding of at least two sodium ions per GABA molecule transported.
A difference in the in vivo cerebral production of [1‐14C] lactate from D‐[3‐14C] glucose in chronic mental patients
Authors: Sacks William , Schechter David C. , Sacks Shirley
Published: January 2005

Data from a study in which 12 chronic mental patients and 12 control subjects were given D‐[3‐14C] glucose intravenously in our arterio‐venous technique for determining cerebral metabolism in vivo were reexamined. Previously unpublished whole‐blood lactate determinations in these experiments indicated a cerebral production of much higher specific activity of [1‐14C]‐lactate from the D‐[3‐14C] glucose by mental patients. Of several possible explanations offered for this difference, the most likely was that involving a small lactate compartments(s) in some specific region(s) in which decarboxylation of the endogenously formed cerebral lactate was partially inhibited. Two other experiments with mental patients (one given [U‐14C] glucose and the other, [1‐14C] glucose) whose extraordinary results were described, in part, in a previous report, were interpreted as more extreme examples of the production of higher specific activity 14C‐lactate from 14C‐glucose by mental patients' brains upon their very unusual whole blood lactate data.
Protective effect of taurine on the light‐induced disruption of isolated frog rod outer segments
Authors: Pasantes‐Morales H. , Ademe R. M. , Quesada O.
Published: January 2005

Isolated frog rod outer segments (ROS) incubated in a Krebs‐bicarbonate medium, and illuminated for 2 h, show a profound alteration in their structure. This is characterized by distention of discs, vesiculation, and a marked swelling. The light‐induced ROS disruption requires the presence of bicarbonate and sodium chloride. Replacement of bicarbonate by TRIS or HEPES protects ROS structure. Also, substitution of sodium chloride by sucrose or choline chloride maintains unaltered the ROS structure. Deletion of calcium, magnesium, or phosphate does not modify the effect produced by illumination. An increased accumulation of labeled bicarbonate and tritiated water is observed in illuminated ROS, as compared with controls in the dark. The presence of taurine, GABA, or glycine, at concentrations of 5–25 mM, effectively counteracts the light‐induced ROS disruption. Taurine (25 mM) reduces labeled bicarbonate and tritiated water levels to those observed in the dark incubated ROS.
Investigations on myelination in vitro. III. Ultrastructural, biochemical, and immunohistochemical studies in cultures of dissociated brain cells from embryonic mice
Authors: Sarliéve L. L. , Delaunoy J. P. , Dierich A. , Ebel A. , Fabre M. , Mandel P. , Rebel G. , Vincendon G. , Wintzerith M. , Yusufi A. N. K.
Published: January 2005

Cerebral hemispheres of 14‐ to 15‐day‐old mouse embryos were dissociated mechanically into single cells and cultured in polylysine‐coated plastic flasks. The succession of changes and the identification of cell populations have been studied by transmission electron microscopy (TEM). Four distinct cell types can be clearly defined. Neuroblasts, oligodendroblasts, and astroblasts were used to denote embryonic states of neurons, oligodendrocytes, and astrocytes. Cell populations were: (1) neuroblasts; (2) astroblasts, either growing on the surface of the flasks and forming a basal layer of epithelioid cells or scattered at the surface of the bed layer; (3) oligodendroblasts, characterized by a high nucleocytoplasmic ratio and resting on top of the bed layer; (4) macrophages. Incorporation of [3H]thymidine into cells at different days in culture (DIC) delineated at least three periods of DNA synthesis (from 1 to 6, from 10 to 20, and from 25 to 60 DIC). High cell RNA/DNA and protein/DNA ratios indicated an increase in the cytoplasmic mass. Guanylate cyclase (EC 4.6.1.2; GC) and adenylate cyclase (EC 4.6.1.1; AC) activities and the ratio AC/GC also agreed with the existence of different periods in culture, but the yin yang hypothesis (postulated by Goldberg et al, 1975) was only partially confirmed. Concerning membrane constituents, the evolution of the pattern of the major gangliosides showed a phase from 1 to 20 DIC which was characterized during the first half of this period by a high percentage of tri‐ and tetra‐sialogangliosides, thereby confirming the presence of well differentiated neurons. Choline acetyltransferase (EC 2.3.1.6; ChAc), acetylcholinesterase (EC 3.1.1.7; AChE), and [3H]muscimol binding (indicative of GABA‐receptors) supported this conclusion. Another phase from 20 to 60 DIC showed a relatively higher content of GM3 and GD3 of the disialogangliosides GD1a and GD1b. These data favor a glial origin of the cells, also demonstrated by TEM and by immunohistochemistry with anti‐glial fibrillary acidic protein (anti‐GFAP) and anti‐carbonic anhydrase isoenzyme II (anti‐CAII; EC 4.2.1.1) sera.

Ultrastructural, biochemical, and immunohistochemical data are in agreement with the existence of successive and different periods of cell proliferation and differentiation which have been defined as: (1) mainly neuronal from 1 to 12 DIC; (2) astroglial and oligodendroglial between 10 and 20 DIC, and (3) possibly microglial from 25 to 40 DIC. This surface‐adhering primary culture system should significantly enhance efforts to examine the roles played by hormones or other effectors in the regulation of myelination.
Uptake of glutamate, GABA, and glutamine into a predominatly GABA‐ergic and a predominantly glutamatergic nerve cell population in culture
Authors: Yu Albert C. H. , Hertz Leif
Published: January 2005

Uptake kinetics for glutamate, GABA, and glutamine were determined in primary cultures of cerebral neurons, a predominatly GABA‐ergic cell population, and of cerebellar granule cells, a predominantly glutamatergic cell population. A specially high Vmax for GABA uptake into the former and for glutamate uptake into the latter cells suggests that considerable amounts of released transmitters may be reaccumulated into appropriate nerve terminals. Nervertheless, the glutamate uptake into the cerebellar granule cells was less intense than that previously observed into corresponding cultures of astrocytes, whereas GABA was accumulated more intensely into neurons than into astrocytes. This suggests that especially glutamatergic neurons may be depleted for their transmitter by accumulation into adjacent astrocytes. If a glutamine flow from astrocytes back to neurons served the purpose of balancing this transfer, it should be expected that glutamine accumulation was more intense in the glutamatergic than in the GABA‐ergic cell population. This was not the case, suggesting that such a glutamate–glutamine cycle may not be operating to a major extent.
Picrotoxin action on the receptive fields of the cat sensorimotor cortex neurons
Authors: Batuev A. S. , Alexandrov A. A. , Scheynikov N. A.
Published: January 2005

The receptive fields of the sensorimotor cortex neurons identified by electrocutaneous stimulation were modified by microelectrophoretically applied picrotoxin which is known to reduce inhibition. A relatively short application of picrotoxin (90 nA during 3–6 min) markedly increased the size of the neuronal receptive fields in the sensorimotor cortex. Control application of glutamate showed that additional depolarization did not affect receptive fields of the spontaneously active units. Our results together with other work in this field further support the hypothesis that inhibitory processes play a major role in forming functional properties of the cerebral cortex neurons.
A neurotrophic factor (NTF) released from primary glial cultures supports survival and fiber outgrowth of cultured hippocampal neurons
Authors: Müller Hans Werner , Seifert Wilfried
Published: January 2005

A nearly pure neuronal culture from embryonic rat brain (hippocampus) has been established in order to observe individual neurons during their in vitro development. This neuronal culture has been used as a test system for a neurotrophic factor (NTF) which is released into a serum‐free defined medium, presumably by astrocytes, the dominant cell type in a primary glial culture from rat brain. NTF is essential for the development of the hippocampal neurons in cell culture. The number of neurons responding to NTF by neurite extension is highly dependent on the concentration of the factor in the culture medium. The amount of factor in serum‐free glial conditioned medium can be estimated in a rapid (20‐hour) bioassay.
Nerve growth factor‐induced stimulation of α‐aminoisobutyric acid uptake in PC 12 cells: Evaluation of its biological significance
Authors: Kedes Dean H. , Gunning Peter W. , Shooter Eric M.
Published: January 2005

In the clonal PC12 pheochromocytoma cell line, the observed effects of nerve growth factor (NGF) on the uptake rates of α‐aminoisobutyric acid (AIB) depend upon the assay conditions employed. In orthodox uptake assays calling for serum removal prior to the addition of AIB, 50 ng/ml NGF causes a stimulation of uptake of 62% after 40 minutes and 46% after 24‐hours exposure. However, serum stimulates AIB uptake to a similar extent and the effects of serum and NGF are not additive. An uptake assay which directly measures the AIB uptake experienced by PC12 cells undergoing NGF‐induced morphological differentiation was therefore employed. When compared with control cells growing in serum‐containing medium, NGF‐induced differentiating PC12 calls experience (1) only a transient and modest increase in AIB uptake, and (2) a significant long‐term decrease in AIB uptake under conditions optimal for differentiation. It is concluded that NGF‐directed neurite outgrowth is not mediated by NGF effects on amino acid uptake via the A‐system.
Nerve growth factor effects and receptors in cultured human neuroblastoma cell lines
Authors: Sonnenfeld Kenneth H. , Ishii Douglas N.
Published: January 2005

We studied the effects of nerve growth factor (NGF) to determine whether neuroblastoma (NB) cells share the pattern of altered response to growth regulatory factors shown by various malignant transformed cells. NGF induces neurite outgrowth, arrests growth, and enhances survival in normal neurons and in the rat pheochromocytoma, a tumor cell closely related to NB. With respect to neurite outgrowth, lines SK‐N‐SH, SH‐SY5Y, LA‐N‐5, and CHP‐126 were sensitive, IMR‐32 was resistant, and SH‐EP1, SK‐N‐MC, MC‐IXC, CHP‐100, and CHP‐134 were unresponsive. Conditioned media from unresponsive cells did not inhibit response in sensitive cells. Unexpectedly, NGF neither reduced the growth rate nor enhanced survival in any NB cell line. Conditioned medium from all NB cell lines enhanced 125I‐NGF binding in embryonic sensory cells. Regulation of growth rate and neurite outgrowth, then, are separable. A fundamental defect in NB may be the acquisition of a capacity for growth and survival independent of NGF. 125I‐NGF was bound to both Fast and Slow receptors in MC‐IXC cells, but only to Slow receptors in NGF‐responsive SH‐SY5Y and LA‐N‐5 cells, showing Fast receptors are not required for neurite outgrowth. Independence from NGF‐regulated growth and survival is unexplainable by an absence of NGF receptors.
Modification of membrane‐bound proteins of the hippocampus and entorhinal cortex by change in behavior in rats
Authors: Hydén Holger , Lange Paul W.
Published: January 2005

Rats were trained in an instrumental task for 2 × 25 min during 1 day and 4 days and compared with active controls with respect to membrane‐bound proteins solubilized by chloral hydrate and fractionated on polyacrylamide gels. Then 30‐μg samples of the hippocampus and entorhinal cortex were labeled by 14C‐and 3H‐valine. The distribution of the stained electrophoretogram was recorded by microdensitometry. The results show that the 1‐day training induced an increased synthesis of a membrane protein fraction of 50,000 mol wt already present in the brain membrane proteins of active controls. Training for 4 days resulted in an overall stimulation of the hippocampal membrane protein fractions, especially in the higher‐molecular‐weight range. The entorhinal cortex showed two stimulated membrane protein fractions, 50,000 and 120,000 mol wt. Together with previous studies, this study makes it probable that training to establish a new behavior induces a modulation of both soluble and membrane‐bound protein patterns in the hippocampus and the entorhinal cortex with a time phase retardation for the latter.
Dose effects of morphine on the spontaneous unit activity recorded from the thalamus, hypothalamus, septum, hippocampus, reticular formation, central gray, and caudate nucleus
Authors: Dafny N. , Burks T. F. , Bergmann F.
Published: January 2005

Spontaneous activity was recorded from 652 units in 8 subcortical structures of unanesthetized rats. Recordings were obtained in central gray, mesencephalic reticular formation, parafasciculus thalami, caudate nucleus, anterior and ventro‐ medial hypothalamus, lateral septum, and dorsal hippocampus. Eighty recordings were obtained from untreated animals and 80 from saline‐injected controls, none of which showed any significant changes of unit activity during the 4‐ 5‐hr observation period. The effect of morphine, given in 5 incremental doses from 0.5 to 30.0 mg/kg ip, was followed in 492 units.

Morphine enhanced or depressed spontaneous discharge rates, or caused biphasic effects, ie enhancement alternating with depression and vice versa. Naloxone induced increase in firing after either effect of morphine, or reduced spontaneous activity after morphineinduced increases. However, when morphine reduced neuronal discharges, naloxone never caused further depression.

In 86 units, morphine at any dosage failed to alter neuronal activity, but in 54 of these units naloxone nevertheless induced alterations in firing rates.

The pattern of responses to morphine differed between all 8 brain regions examined and was characteristic for each individual structure. This is the first systematic study describing the dose‐response characteristics of morphine in 8 brain sites recorded simultaneously. Furthermore, it utilized freely behaving animals without the interference of anesthetics, which are themselves known to interact with opiates. The variety of response patterns seen supports the neuro pharmacological evidence for multiple opiate receptors or multiple sites of opiate action.
Studies on acetylcholinesterase and gamma‐glutamyltranspeptidase in mouse brain in ammonia toxicity
Authors: Sadasivudu B. , Murthy C. R. K. , Rao G. N. , Swamy M.
Published: January 2005

Short‐ and long‐term ammonia toxicity was induced in mice by intraperitoneal injection, respectively, of single and six doses of 0.6 mM ammonium acetate per 100 g of body weight. The animals were sacrificed half an hour after either the single injection or after the last injection of six doses. Under these experimental conditions the ammonia levels were found to be elevated twofold in cerebral cortex, brain stem, and basal ganglia after the administration of a single dose of ammonium acetate. A fourfold increase in the content of ammonia was observed in cerebral cortex, brain stem, and basal ganglia after six injections. An elevation in the activity of pseudocholinesterase (enzyme localized in brain capillaries and dial cells) in all the above four regions resulted as a short‐term effect of ammonia toxicity. True acetylcholinesterase was found to be elevated in all the four regions in short‐term and in long‐term ammonia toxicity. Gamma‐glutamyltranspeptidase (GGTP), another enzyme localized in cerebral capillaries and glial cells, was found to be depressed in all the regions of the brain in both short‐ and long‐term ammonia toxicity. The implications of these results are discussed in relation to glial cell function.