Enhanced dopamine D2 receptor function in hypothalamus and corpus striatum: their role in liver, plasma and in vitro hepatocyte ALDH regulation in ethahol treated rats

Dopamine D2 receptors are involved in ethanol self- administration behavior and also suggested to mediate the onset and offset of ethanol drinking. In the present study, we investigated dopamine (DA) content and Dopamine D2 (DA D2) receptors in the hypothalamus and corpus striatum of ethanol treated rats and aldehyde dehydrogenase (ALDH) activity in the liver and plasma of ethanol treated rats and in vitro hepatocyte cultures. Hypothalamic and corpus striatal DA content decreased significantly (P\0.05, P\0.001 respectively) and homovanillic acid/ dopamine (HVA/DA) ratio increased significantly (P\0.001) in ethanol treated rats when compared to control. Scatchard analysis of [3H] YM-09151-2 binding to DA D2 receptors in hypothalamus showed a significant increase (P\0.001) in Bmax without any change in Kd in ethanol treated rats compared to control. The Kd of DA D2 receptors significantly decreased (P\0.05) in the corpus striatum of ethanol treated rats when compared to control. DA D2 receptor affinity in the hypothalamus and corpus striatum of control and ethanol treated rats fitted to a single site model with unity as Hill slope value. The in vitro studies on hepatocyte cultures showed that 10-5 M and 10-7 M DA can reverse the increased ALDH activity in 10% ethanol treated cells to near control level. Sulpiride, an antagonist of DA D2, reversed the effect of dopamine on 10% ethanol induced ALDH activity in hepatocytes. Our results showed a decreased dopamine concentration with enhanced DA D2 receptors in the hypothalamus and corpus striatum of ethanol treated rats. Also, increased ALDH was observed in the plasma and liver of ethanol treated rats and in vitro hepatocyte cultures with 10% ethanol as a compensatory mechanism for increased aldehyde production due to increased dopamine metabolism. A decrease in dopamine concentration in major brain regions is coupled with an increase in ALDH activity in liver and plasma, which contributes to the tendency for alcoholism. Since the administration of 10-5 M and 10-7 M DA can reverse the increased ALDH activity in ethanol treated cells to near control level, this has therapeutic application to correct ethanol addicts from addiction due to allergic reaction observed in aldehyde accumulation.

Characterization of the molecular clockwork in the cockroach Rhyparobia maderae

Der Wechsel von Tag und Nacht erzeugt einen regelmäßigen Rhythmus von verschiedenen Umweltreizen, allen voran Licht und Temperatur. Fast jedes bis zum heutigen Tage untersuchte Lebewesen besitzt einen endogenen Mechanismus zur Zeitwahrnehmung, und diese "innere Uhr" befähigt Lebewesen dazu, sich vorausschauend an rhythmische Umwelt-Änderungen anzupassen. Circadiane Rhythmen bestehen auch ohne jegliche äußere Reize und basieren auf einem molekularen Rückkopplungs-Mechanismus, der Rhythmen in Genexpression und Proteinkonzentration von etwa 24 Stunden erzeugt. Obwohl sich die grundsätzlichen Mechanismen und Komponenten dieses molekularen Uhrwerks in allen Insekten ähneln, zeigte sich jedoch immer mehr, dass es im Detail doch wesentliche Unterschiede zwischen verschiedenen Insektengruppen gibt. Während das molekulare Uhrwerk der Fruchtfliege Drosophila melanogaster inzwischen sehr gut untersucht ist, fehlen bei den meisten Insektengruppen immernoch eingehende Untersuchungen. Fast nichts ist über die molekulare Basis von circadianen Rhythmen bei der Schabe Rhyparobia maderae bekannt, obwohl diese Art bereits seit Langem als Modellorganismus in der Chronobiologie dient. Um mit der Forschung am molekularen, circadianen System von R. maderae zu beginnen, wurde die Struktur und das Expressionsprofil der core feedback loop Gene per, tim1 und cry2 analysiert. Mittels degenerierten Primern und RACE konnte das vollständige offene Leseraster (OLR) von rmPer und rmCry2, und ein Teil des rmTim1 OLR kloniert werden. Eine phylogenetische Analyse gruppierte rmPER und rmCRY2 gemeinsam mit den Orthologa hemimetaboler Insekten. Viele bei D. melanogaster funktionell charakterisierte Domänen sind bei diesen Proteinen konserviert, was auf eine ähnliche Funktion in der inneren Uhr von R. maderae hinweist. Mittels quantitativer PCR konnte gezeigt werden, dass die mRNA von rmPer, rmTim1 und rmCry2 in verschiedenen Lichtregimen in der gleichen Phasenlage Tageszeit-abhängig schwankt. Die Phasenlage stellte sich bei unterschiedlichen Photoperioden jeweils relativ zum Beginn der Skotophase ein, mit Maxima in der ersten Hälfte der Nacht. Auch im Dauerdunkel zeigen sich Rhythmen in der rmTim1 und rmCry2 Expression. Die Amplitude der rmPer Expressionsrhythmen war jedoch so gering, dass keine signifikanten Unterschiede zwischen den einzelnen Zeitgeberzeiten (ZT) festgestellt werden konnten. Mittels Laufrad-Assays wurde untersucht wie Kurz- und Langtag Lichtregime die Verhaltensrhythmen beeinflussen. Es konnten nur Unterschiede in der Periodenlänge unter freilaufenden Bedingungen festgestellt werden, wenn höhere Lichtintensitäten (1000lx) zur Synchronisation (entrainment) genutzt wurden. Die Periode des freilaufenden Rhythmus war bei Tieren aus dem Kurztag länger. Die photoperiodische Plastizität zeigte sich also auch auf Verhaltensebene, obwohl höhere Lichtintensitäten notwendig waren um einen Effekt zu beobachten. Basierend auf den Sequenzen der zuvor klonierten OLR wurden gegen rmPER, rmTIM1 und rmCRY2 gerichtete Antikörper hergestellt. Die Antikörper gegen rmPER und rmTIM1 erkannten in western blots sehr wahrscheinlich spezifisch das jeweilige Protein. Zeitreihen von Gehirngewebe-Homogenisaten zeigten keinen offensichtlichen circadianen Rhythmus in der Proteinkonzentration, wahrscheinlich auf Grund einer Oszillation mit niedriger Amplitude. In Immunhistochemischen Färbungen konnte nur mit dem gegen rmPER gerichteten Antikörper aus Kaninchen ein Signal beobachtet werden. Beinahe jede Zelle des Zentralnervensystems war rmPER-immunreaktiv im Zellkern. Es konnten keine Unterschiede zwischen den untersuchten ZTs festgestellt werden, ähnlich wie bei den western blot Zeitreihen. In dieser Studie konnten erstmals molekulare Daten der circadianen Uhr von R. maderae erfasst und dargestellt werden. Die Uhrgene per, tim1 und cry2 werden in dieser Schabenart exprimiert und ihre Domänenstruktur sowie das circadiane Expressionsmuster ähneln dem hypothetischen ursprünglichen Insektenuhrwerk, welches der circadianen Uhr von Vertebraten nahesteht. Das molekulare Uhrwerk von R. maderae kann sich an unterschiedliche Photoperioden anpassen, und diese Anpassungen manifestieren sich im Expressionsprofil der untersuchten Uhrgene ebenso wie im Verhalten.

Signaling of Pigment-Dispersing Factor (PDF) in the Madeira Cockroach Rhyparobia maderae

The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca2+ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca2+ baseline concentration and frequency of oscillating Ca2+ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca2+ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1–4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca2+ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K+ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K+ and Na+ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance.

The function of SIFamide, PDF, and further neuropeptides in the circadian system of Rhyparobia maderae

Der täglich Wechsel von Hell- und Dunkelphasen führte während der Evolution zur Entwicklung innerer Uhren in nahezu allen Organismen. In der Schabe Rhyparobia maderae lokalisierten Läsions- und Transplantationsexperimente die innere Uhr in der akzessorischen Medulla (AME). Dieses kleine birnenförmige Neuropil am ventromedianen Rand der Medulla ist mit etwa 240 Neuronen assoziiert, die eine hohe Anzahl an zum Teil kolokalisierten Neuropeptiden und Neurotransmittern exprimieren. Diese Signalstoffe scheinen essentiell zu sein für die Synchronisation der inneren Uhr mit der Umwelt, der Kopplung der beiden bilateralen AME, der Aufrechterhaltung des circadianen Rhythmus sowie der zeitlichen Steuerung bestimmter Verhaltensweisen. Während die Funktion einiger dieser neuronalen Botenstoffe bereits gut untersucht ist, fehlt sie für andere. Zudem ist noch ungeklärt, wann einzelne Botenstoffe im circadianen Netzwerk agieren. Im Fokus dieser Studie lag daher die Erforschung der Funktion von SIFamide und Corazonin im circadianen Netzwerk sowie die weitere Untersuchung der Funktionen der Neuropeptide MIP und PDF. Es konnte gezeigt werden, dass SIFamide auch in R. maderae in vier großen neurosekretorischen Zellen in der pars intercerebralis exprimiert wird. Varikosenreiche SIFamide-immureaktive (-ir) Fasern innervieren eine Vielzahl an Neuropilen und finden sich auch in der Hüllregion der AME. Injektionsexperimente resultierten in einer monophasischen Phasen-Antwort-Kurve (PRC) mit einer Verzögerung zur frühen subjektiven Nacht. SIFamide ist also ein Eingangssignal für das circadiane Netzwerk und könnte in der Kontrolle der Schalf/Wach-Homöostase involviert sein. Auch Corazonin fungiert als Eingangssignal. Da die Injektionsexperimente in einer monophasischen PRC mit einem Phasenvorschub zur späten subjektiven Nacht resultierten, ist davon auszugehen, dass die Corazonin-ir AME-Zelle Bestandteil des Morning-Oszillator-Netzwerkes in R. maderae ist. Darüber hinaus zeigten Backfill-Experimente, dass MIP an der Kopplung beider AMAE beteiligt ist. ELISA-Quantifizierungen der PDF-Level im Tagesverlauf ergaben Schwankungen in der Konzentration, die auf eine Ausschüttung des Peptids während des Tages hindeuten – ähnlich wie es in Drosophila melanogaster der Fall ist. Dies spiegelt sich in der vervollständigten bimodalen PDF-PRC wieder. Hier führen Injektionen zu einem Phasenvorschub, bevor maximale Peptidlevel erreicht werden, sowie zu einer Phasenverzögerung, sobald die Peptidlevel wieder zu sinken beginnen. Die PRCs erlauben somit Rückschlüsse auf den Zeitpunkt der maximalen Peptidfreisetzung. PDF-ir Neuriten findet sich zudem in sämtlichen Ganglien des ventralen Strickleiternervensystems, was eine Funktion in der Kontrolle der Prozesse impliziert, die durch die Mustergeneratoren in Thorakal- und Abdominalganglien gesteuert werden.

16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus

Background: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naive mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intracerebra-ventricularly (ICV) with the 16/6-Id antibody. Methods: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes. Results: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control. Conclusions: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.

Developmental changes in presynaptic muscarinic modulation of excitatory and inhibitory neurotransmission in rat piriform cortex in vitro: relevance to epileptiform bursting susceptibility

Suppression of depolarizing postsynaptic potentials and isolated GABA-A receptor-mediated fast inhibitory postsynaptic potentials by the muscarinic acetylcholine receptor agonist, oxotremorine-M (10 microM), was investigated in adult and immature (P14-P30) rat piriform cortical (PC) slices using intracellular recording. Depolarizing postsynaptic potentials evoked by layers II-III stimulation underwent concentration-dependent inhibition in oxotremorine-M that was most likely presynaptic and M2 muscarinic acetylcholine receptor-mediated in immature, but M1-mediated in adult (P40-P80) slices; percentage inhibition was smaller in immature than in adult piriform cortex. In contrast, compared with adults, layer Ia-evoked depolarizing postsynaptic potentials in immature piriform cortex slices in oxotremorine-M, showed a prolonged multiphasic depolarization with superimposed fast transients and spikes, and an increased 'all-or-nothing' character. Isolated N-methyl-d-aspartate receptor-mediated layer Ia depolarizing postsynaptic potentials (although significantly larger in immature slices) were however, unaffected by oxotremorine-M, but blocked by dl-2-amino-5-phosphonovaleric acid. Fast inhibitory postsynaptic potentials evoked by layer Ib or layers II-III-fiber stimulation in immature slices were significantly smaller than in adults, despite similar estimated mean reversal potentials ( approximately -69 and -70 mV respectively). In oxotremorine-M, only layer Ib-fast inhibitory postsynaptic potentials were suppressed; suppression was again most likely presynaptic M2-mediated in immature slices, but M1-mediated in adults. The degree of fast inhibitory postsynaptic potential suppression was however, greater in immature than in adult piriform cortex. Our results demonstrate some important physiological and pharmacological differences between excitatory and inhibitory synaptic systems in adult and immature piriform cortex that could contribute toward the increased susceptibility of this region to muscarinic agonist-induced epileptiform activity in immature brain slices.

Understanding the effects of anesthetic agents on the EEG through neural field theory

Anesthetic and analgesic agents act through a diverse range of pharmacological mechanisms. Existing empirical data clearly shows that such "microscopic" pharmacological diversity is reflected in their "macroscopic" effects on the human electroencephalogram (EEG). Based on a detailed mesoscopic neural field model we theoretically posit that anesthetic induced EEG activity is due to selective parametric changes in synaptic efficacy and dynamics. Specifically, on the basis of physiologically constrained modeling, it is speculated that the selective modification of inhibitory or excitatory synaptic activity may differentially effect the EEG spectrum. Such results emphasize the importance of neural field theories of brain electrical activity for elucidating the principles whereby pharmacological agents effect the EEG. Such insights will contribute to improved methods for monitoring depth of anesthesia using the EEG.

Beyond arousal and valence: the importance of the biological versus social relevance of emotional stimuli

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention, memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images’ subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in the visual cortex and greater functional connectivity between the amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.

Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour

Several recent studies have shown that reducing gamma-aminobutyric acid (GABA)-mediated neurotransmission retards extinction of aversive conditioning. However, relatively little is known about the effect of GABA on extinction of appetitively motivated tasks. We examined the effect of chlordiazepoxide (CDP), a classical benzodiazepine (BZ) and two novel subtype-selective BZs when administered to male C57Bl/6 mice during extinction following training on a discrete-trial fixed-ratio 5 (FR5) food reinforced lever-press procedure. Initially CDP had no effect, but after several extinction sessions CDP significantly facilitated extinction, i.e. slowed responding, compared with vehicle-treated mice. This effect was not due to drug accumulation because mice switched from vehicle treatment to CDP late in extinction showed facilitation immediately. Likewise, this effect could not be attributed to sedation because the dose of CDP used (15 mg/kg i.p.) did not suppress locomotor activity. The two novel subtype-selective BZ partial agonists, L-838417 and TP13, selectively facilitated extinction in similar fashion to CDP. The non-GABAergic anxiolytic buspirone was also tested and found to have similar effects when administered at a non-sedating dose. These studies demonstrate that GABA-mediated processes are important during extinction of an appetitively motivated task, but only after the animals have experienced several extinction sessions.

Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice

The GPR30, a former orphan GPCR, is a putative membrane estrogen receptor that can activate rapid signaling pathways such as extracellular regulated kinase (ERK) in a variety of cells and may contribute to estrogen's effects in the central nervous system. The distribution of GPR30 in the limbic system predicts a role for this receptor in the regulation of learning and memory and anxiety by estrogens. Though acute G-1 treatment is reported to be anxiogenic in ovariectomised female mice and in gonadally intact male mice, the effect of GPR30 activation is unknown in gonadectomised male mice. In this study, we show that an acute administration of G-1 to gonadectomised male mice, but not female mice, was anxiolytic on an elevated plus maze task, without affecting locomotor activity. In addition, though G-1 treatment did not regulate ERK, it was associated with increased estrogen receptor (ER)alpha phosphorylation in the ventral, but not dorsal, hippocampus of males. In the female, G-1 increased the ERK activation solely in the dorsal hippocampus, independent of state anxiety. This is the first study to report an anxiolytic effect of GPR30 activation in male mice, in a rapid time frame that is commensurate with non-genomic signaling by estrogen.

Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses

This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 mu g/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.

Cardiovascular and autonomic phenotype of db/db diabetic mice

The db/db mice serve as a good model for type 2 diabetes characterized by hyperinsulinaemia and progressive hyperglycaemia. There are limited and conflicting data on the cardiovascular changes in this model. The aim of the present study was to characterize the cardiovascular and autonomic phenotype of male db/db mice and evaluate the role of angiotensin II AT(1) receptors. Radiotelemetry was used to monitor 24 h blood pressure (BP) in mice for 8 weeks. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and their variabilities. In 8-week-old db/db mice, the MAP and BP circadian rhythms were not different from age-matched control mice, while HR and locomotor activity were decreased. With ageing, MAP gradually increased in db/db mice, and the 12 h light values did not dip significantly from the 12 h dark periods. In 14-week-old mice, MAP was increased during light (101 +/- 1 versus 117 +/- 2 mmHg, P < 0.01; control versus db/db mice) and dark phases (110 +/- 1.7 versus 121 +/- 3.1 mmHg, P < 0.01; control versus db/db mice). This increase in MAP was associated with a significant increase in plasma angiotensin-converting enzyme activity and angiotensin II levels. Chronic treatment with losartan (10 mg kg(-1) day(-1)) blocked the increase in MAP in db/db mice, with no effect in control animals. Spectral analysis was used to monitor autonomic cardiovascular function. The circadian rhythm observed in systolic arterial pressure variance and its low-frequency component in control mice was absent in db/db mice. There were no changes in HR variability and spontaneous baroreflex sensitivity between control and db/db mice. The results document an age-related increase in MAP in db/db mice, which can be reduced by antagonism of angiotensin II AT(1) receptors, and alterations in autonomic balance and components of the renin-angiotensin system.

Circadian phase and intertrial interval interfere with social recognition memory

A modified version of the social habituation/dis-habituation paradigm was employed to examine social recognition memory in Wistar rats during two opposing (active and inactive) circadian phases, using different intertrial intervals (30 and 60 min). Wheel-running activity was monitored continuously to identify circadian phase. To avoid possible masking effects of the light-dark cycle, the rats were synchronized to a skeleton photoperiod, which allowed testing during different circadian phases under identical lighting conditions. In each trial, an infantile intruder was introduced into an adult`s home-cage for a 5-minute interaction session, and social behaviors were registered. Rats were exposed to 5 trials per day for 4 consecutive days: oil days I and 2, each resident was exposed to the same intruder; on days 3 and 4, each resident was exposed to a different intruder in each trial. I he resident`s social investigatory behavior was more intense when different intruders were presented compared to repeated presentation of the same intruder, suggesting social recognition memory. This effect was stronger when the rats were tested during the inactive phase and when the intertrial interval was 60 min, These findings Suggest that social recognition memory, as evaluated in this modified habituation/dis-habituation paradigm, is influenced by the circadian rhythm phase during which testing is performed, and by intertrial interval. (C) 2008 Elsevier Inc. All rights reserved.

Increase in Hippocampal Theta Oscillations during Spatial Decision Making

The processing of spatial and mnemonic information is believed to depend on hippocampal theta oscillations (5–12 Hz). However, in rats both the power and the frequency of the theta rhythm are modulated by locomotor activity, which is a major confounding factor when estimating its cognitive correlates. Previous studies have suggested that hippocampal theta oscillations support decision-making processes. In this study, we investigated to what extent spatial decision making modulates hippocampal theta oscillations when controlling for variations in locomotion speed. We recorded local field potentials from the CA1 region of rats while animals had to choose one arm to enter for reward (goal) in a four-arm radial maze. We observed prominent theta oscillations during the decision-making period of the task, which occurred in the center of the maze before animals deliberately ran through an arm toward goal location. In speed-controlled analyses, theta power and frequency were higher during the decision period when compared to either an intertrial delay period (also at the maze center), or to the period of running toward goal location. In addition, theta activity was higher during decision periods preceding correct choices than during decision periods preceding incorrect choices. Altogether, our data support a cognitive function for the hippocampal theta rhythm in spatial decision making

Effects of elevated calcium on motor and exploratory activities of rats

The effects of serum and brain calcium concentration on rat behavior were tested by maintaining animals on either distilled water (N = 60) or water containing 1% calcium gluconate (N = 60) for 3 days. Animals that were maintained on high calcium drinking water presented increased serum calcium levels (control = 10.12 ± 0.46 vs calcium treated = 11.62 ± 0.51 µg/dl). Increase of brain calcium levels was not statistically significant. In the behavioral experiments each rat was used for only one test. Rats that were maintained on high calcium drinking water showed increased open-field behavior of ambulation (20.68%) and rearing (64.57%). on the hole-board, calcium-supplemented animals showed increased head-dip (67%) and head-dipping (126%), suggesting increased ambulatory and exploratory behavior. The time of social interaction was normal in animals maintained on drinking water containing added calcium. Rats supplemented with calcium and submitted to elevated plus-maze tests showed a normal status of anxiety and elevated locomotor activity. We conclude that elevated levels of calcium enhance motor and exploratory behavior of rats without inducing other behavioral alterations. These data suggest the need for a more detailed analysis of several current proposals for the use of calcium therapy in humans, for example in altered blood pressure states, bone mineral metabolism disorders in the elderly, hypocalcemic states, and athletic activities.