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Biomedical subjects

C Sandi

Publications and source records attributed to C Sandi.

At least 37 records · Page 2Linked to original sources
PubMed1997

The corticosteroid synthesis inhibitors metyrapone and aminoglutethimide impair long-term memory for a passive avoidance task in day-old chicks.

Long-term memory for a passive avoidance task in day-old chicks has proved to depend upon an action of the adrenal steroid corticosterone through specific receptors in a brain region, the intermediate medial hyperstriatum ventrale (IMHV), involved in learning the task. In this study, we questioned whether pretraining peripheral administration of drugs described to inhibit either basal levels of corticosterone - aminoglutethimide - or treatment-induced stimulated corticosterone secretion - metyrapone - might interfere with retention for the task at 24 h post-training. The results showed a dose-dependent effect of the inhibitors, with the highest doses tested for both drugs (10 and 50 mg/kg for metyrapone, and 50 mg/kg for aminoglutethimide) being amnestic for the task. Additional experiments, in which we studied possible effects of the inhibitors on concomitant aspects of learning (i.e., reactivity to novelty, and pecking pattern), show that the drugs did not affect general behavioural reactivity. The present results thus support the idea that training-induced corticosterone release plays a key role in the neurobiological processes that determine the establishment of a persistent memory for the aversively motivated avoidance response. In addition, they point to corticosteroid inhibitor drugs as potential tools for the study of the interactions between steroid hormones and cognition-enhancing compounds in this learning task.

Adrenal Cortex Hormones↗
PubMed1997

Interactions of corticosterone and embryonic light deprivation on memory retention in day-old chicks.

Corticosterone, injected embryonically into eggs hatched in the dark, improved retention for a weak passive avoidance task in day-old chicks, the optimal time points for injection were days E19 to E20, resembling those found previously for light exposure, suggesting possible interactions between light and corticosterone during late embryonic development with consequent effects on post-hatch behaviour.

Animals↗
PubMed1997

Training-dependent biphasic effects of corticosterone in memory formation for a passive avoidance task in chicks.

This study investigates the functional role of corticosterone in memory formation for a passive avoidance task in the day-old chick. Whereas training chicks with a strong aversant results in an enduring memory, memory for a weak aversant which is only retained for a few hours (< 9 h) is facilitated by intracerebral corticosterone administration. We now report that only chicks trained on the strong task, a learning situation that results in a high percentage of chicks (around 80%) forming a long-term memory, showed increased post-training plasma corticosterone levels, whereas chicks trained on the weak task showed corticosterone values comparable to untrained chicks. We also questioned whether the effects of corticosterone on retention might be concentration dependent. In the weak task, intracerebral administration of 1 microgram corticosterone facilitated retention, but a higher dose failed to induce this effect. However, in the strong task, corticosterone administration at doses of 1 and 5 micrograms produced an impairment in long-term retention for the avoidance response. These results support a crucial role of corticosterone release following training on the physiological mechanisms ensuring the transition from short- to long-term memory, and provide an animal learning model for the study of the mechanisms of action of a biphasic modulation of memory formation by acute corticosterone administration.

Animals↗
PubMed1997

Protein synthesis- and fucosylation-dependent mechanisms in corticosterone facilitation of long-term memory in the chick.

Long-term memory formation for a passive avoidance task in day-old chicks, which requires a late phase of glycoprotein fucosylation (5-8 hr posttraining), is dependent on a corticosterone action in the brain. In addition, corticosterone enhances late-phase fucosylation. In this study, the authors explored (a) to what extent the memory-facilitating action of corticosterone is dependent on protein fucosylation and (b) whether a protein synthesis mechanism might be involved in the steroid effects on memory and late-phase fucosylation. A combination of psychopharmacological and biochemical experiments, including the fucosylation inhibitor 2-deoxygalactose (2-DG), the protein synthesis inhibitor anisomycin (ANI), and radiolabeled fucose, indicated that the late phase of glycoprotein synthesis involved in the memory-facilitating effect of corticosterone occurs on newly synthesized proteins.

Animals↗
PubMed1997

Effects of NMDA and AMPA receptor antagonists on corticosterone facilitation of long-term memory in the chick.

Long-term memory formation for a weak passive avoidance task in day-old chicks is facilitated by corticosterone administration. Since (i) glutamatergic systems, through different receptor types, play a key role in learning and memory processes, and (ii) glucocorticoids increase glutamate concentrations in learning-related regions of the mammalian brain, we reasoned that glutamatergic activation might be a mechanism by which corticosterone facilitates the formation of an enduring memory. To assess this hypothesis, long-term retention was evaluated in chicks trained on a weak passive avoidance task and intracerebrally injected with NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) with regard to training and corticosterone injection respectively. The results indicated that either of the antagonists prevented the facilitating effect of corticosterone when administered before the training trial, but failed to interfere with the steroid effect when injected before corticosterone administration in the post-training period, suggesting that their early effectiveness was not related to corticosterone-induced actions but to training-triggered mechanisms. In addition, administration of the AMPA antagonist, 5.5 h after training, was also effective in impairing the long-term memory-potentiating effect of corticosterone. These results support the view that corticosterone facilitates the formation of an enduring memory in this learning model, through the modulation of late events during the consolidation period, including the activation of the AMPA receptor type.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Experience-dependent facilitating effect of corticosterone on spatial memory formation in the water maze.

Stress-related adrenal steroid hormones modulate brain and cognitive function. Electrophysiological studies, including primed burst potentiation and long-term potentiation, have indicated concentration-dependent inverted U-shape effects of corticosterone in hippocampal function and plasticity. Here, we explored the role of corticosterone in the consolidation and long-term retrieval of spatial learning in the Morris water maze task in rats. We postulated that corticosterone actions might be experience-dependent with regard to stimulus intensity, such as differential water temperatures. Indeed, rats trained at 19 degrees C showed a quicker rate of acquisition and better long-term retention than rats trained at 25 degrees C water. In addition, post-training corticosterone levels, on the first training day, were significantly higher in rats in the 19 degrees C group than in the 25 degrees C group. Performance of rats trained at 25 degrees C, but not at 19 degrees C, water was improved by injecting them i.p. with corticosterone immediately after each training session. Thus, the effect of exogenously administered corticosterone appears to be experience-dependent, with the experience-induced corticosterone concentrations as a critical factor determining the cognitive consequences of steroid treatment. Therefore, this work indicates a facilitating corticosterone action, during the post-training period, on the neural mechanisms determining the strength of information storage under acute, physiological conditions.

Analysis of Variance↗
PubMed1996

Regional and temporal modulation of brain glycoprotein synthesis by corticosterone.

Corticosterone has a biphasic effect on memory formation, short-term effects being facilitating and long-term effects resulting in cognitive impairments. The effects of different patterns of temporal exposure to corticosterone-previously shown to biphasically modulate water maze performance-on glycoprotein synthesis were evaluated in four rat brain regions: hippocampus, striatum, frontal cortex and hypothalamus. Acute corticosterone administration resulted in decreased glycoprotein synthesis in hippocampus and striatum, which might be related to the memory facilitating effects of the steroid. However, sustained exposure to corticosterone in a subchronic (7 days) or chronic (21 days) regimen indicated the hypothalamus as the only region displaying reduced fucosylation after chronic treatment. These findings suggest that detrimental effects of chronic corticosterone treatment on hippocampal neurones and memory might be not related to an initial steroid action on fucosyl-glycoprotein expression.

Animals↗
PubMed1996

Fibroblast growth factor decreases locomotor activity in rats.

The spontaneous locomotor behavior of rats receiving subcutaneous administration of either acidic or basic fibroblast growth factors was recorded in an activity cage. We report that doses between 1 and 100 micrograms/kg significantly decreased the horizontal and vertical activity, as well as the exploratory and stereotypy behavior of the rats. These effects of fibroblast growth factors seem to be specific since (i) they were cancelled by protein hydrolysis and anti-fibroblast growth factor antibodies, (ii) they were unrelated to their hypotensive activity and (iii) they were not attributable to their high structural similarity with the cytokine interleukin-1. Thus fibroblast growth factors did not show any thermogenic activity, did not affect the hypothalamic output of corticotropin-releasing factor and did not change the plasma levels of corticosterone. Pretreatment of the rats with a specific inhibitor of brain nitric oxide synthase prevented the effects of fibroblast growth factors, suggesting the involvement of nitric oxide in these behavioral modifications. Our results contribute to the accumulating evidence describing non-mitogenic activities of fibroblast growth factors.

Animals↗
PubMed1996

Novelty-related rapid locomotor effects of corticosterone in rats.

Glucocorticoids modulate brain function and behaviour through different mechanisms. Although classical effects are mediated through intracellular receptors that modulate gene transcription, recent evidence supports the existence of rapid, nongenomic steroid effects through the neuronal membrane. In this study, we explored possible rapid behavioural effects of corticosterone in the rat, which could provide a model to characterize further the mechanisms involved in rapid corticosteroid nongenomic actions. We found that a corticosterone injection, at doses (2.5 or 5 mg/kg) that mimic plasma concentrations produced by substantial stress, rapidly increases (within 7.5 min of its systemic administration) the locomotor response displayed by rats in a novel environment (activity cage). A lower dose of 1 mg/kg failed to induce this effect. In addition, corticosterone failed to increase locomotion when administered to rats that had been previously exposed to the activity cage. Corticosterone-induced increased locomotion in a novelty situation was not counteracted by either the intracerebroventricular administration of the protein synthesis inhibitor cycloheximide, or by the intracerebroventricular administration of specific antagonists for each type of intracellular corticosteroid receptor, i.e. RU28318, a mineralocorticoid receptor antagonist and RU38486, a glucocorticoid receptor antagonist. Further studies supported the viability of the receptor antagonists to display an anti-corticosteroid action interfering, as previously reported, with the behavioural &winning test. Therefore, the rapid actions of corticosterone in locomotor activity described here, which appear to be nongenomic, might provide a model for future research on the elucidation of the mechanisms involved in steroid-membrane interactions.

Animals↗
PubMed1996

Nitric oxide synthesis inhibitors prevent rapid behavioral effects of corticosterone in rats.

Corticosteroid actions at the brain can modulate neural function and behavioral processes. Classic corticosteroid effects are mediated through intracellular receptors which act primarily by regulation of DNA transcription. However, an alternative nongenomic mechanism mediating rapid corticosteroid actions by effecting the neuronal membrane has also been proposed. We have recently described a behavioral model of rapid corticosterone effects fulfilling criteria for considering nongenomic steroid actions, such as resistance to protein synthesis inhibition and to blockage of intracellular receptors through the use of specific receptor antagonists. The model consists of a rapid increase induced by a corticosterone injection (within 7.5 min of a systemic injection) on the locomotor response displayed by rats in a novel environment. In the present study, we aimed to study whether the gas molecule nitric oxide might be included among the effector systems involved in such rapid corticosterone effect. The administration of nitric oxide synthase inhibitors, given either systemically [NG-nitro-L-arginine methyl ester (L-NAME), 30 mg/kg body weight, i.p.] or centrally [N-nitro-L-arginine (N-Arg), 10 microliters of a 10-mM solution i.c.v.], prevented the increase in locomotion induced by corticosterone (Cort, 5 mg/kg body weight i.p.). Specificity of this effect was supported by the ability of the nitric oxide precursor L-arginine (L-Arg, 350 mg/kg body weight i.p.) to inhibit L-NAME action. This effect of nitric oxide synthase inhibition on steroid effects was shown to be task-specific, since L-NAME failed to influence another rapid behavioral effect of corticosterone, the suppression of the acoustic startle response. Under our experimental conditions, corticosterone failed to affect peripheral blood pressure, discarding that the antagonistic effect of nitric oxide synthase inhibition on the corticosterone-induced effect in locomotion were related to a peripheral action at the cardiovascular level. Therefore, these data suggest a role for nitric oxide on the neurochemical mechanisms elicited by corticosterone to rapidly enhance locomotion in a novel situation.

Acoustic Stimulation↗
PubMed1995

Decreased spontaneous motor activity and startle response in nitric oxide synthase inhibitor-treated rats.

In the central nervous system, nitric oxide has been proposed to be a retrograde messenger mediating learning and synaptic plasticity. Since only pretraining injections of nitric oxide synthesis inhibitors were shown to impair learning, we examined the possibility that systemic administration of these inhibitors might influence some non-specific aspects related to the organism's general psychophysiological status. Intraperitoneal administration of NG-nitro-L-arginine methyl ester (30 or 100 mg/kg) 60 min pre-test to adult rats resulted in: (i) altered exploratory pattern and reduced locomotion in a novel environment; (ii) reduced startle response to either acoustic or electric stimuli; and (iii) cardiovascular alterations. In addition, intracerebroventricular administration of N-nitro-L-arginine (10 microliters of a 10 mM solution) diminished the acoustic startle response. Specificity of these effects through nitric oxide was supported by the ability of the nitric oxide precursor, L-arginine, to prevent the inhibitors actions. These findings indicate that nitric oxide inhibitors interfere with the general psychophysiological status of the organism.

Acoustic Stimulation↗
PubMed1995

Evidence for a role of nitric oxide in the corticotropin-releasing factor release induced by interleukin-1 beta.

Interleukin-1 beta stimulates corticotropin-releasing factor (CRF) secretion from the hypothalamus involving the activation of prostaglandins. This study investigated the possibility that nitric oxide (NO) acts as a mediator of interleukin-1-induced CRF release. An in vitro rat hypothalami continuous perifusion system was used. Pre- and co-incubation of hypothalami with either the NO synthase inhibitor, NG-nitro-L-arginine (1 mM), or the NO scavenger, hemoglobin (10 microM), induced a marked reduction in the effect of interleukin-1 (3 pM) on CRF secretion. The effect of NG-nitro-L-arginine was prevented by pre-exposure of hypothalami to L-arginine (1 mM). We also studied whether the involvement of NO in this interleukin-1 effect could involve a prostaglandin action. The concurrent treatment with NG-nitro-L-arginine and indomethacin (14 microM)--an inhibitor of prostaglandin production--reduced interleukin-1-induced CRF release to the same level as NG-nitro-L-arginine alone, suggesting that prostaglandins might interact with NO on this interleukin-1 effect. These results suggest that NO plays a role in the in vitro stimulatory action of interleukin-1 on hypothalamic CRF secretion.

Analysis of Variance↗
PubMed1995

Corticosterone facilitates long-term memory formation via enhanced glycoprotein synthesis.

Long-term memory formation for a passive avoidance task in one-day-old chicks requires a late phase of synaptic glycoprotein synthesis (including the neural cell adhesion molecule), commencing 5.5 h post-training. This phase occurred in chicks trained with a strong, but not a weak aversant, which only retained this memory for a few hours (< 10). In addition, previous work has shown that a corticosteroid action through central corticosteroid receptors is also required for long-term passive avoidance memory. Here, we tested the hypothesis that the corticosteroid action on memory formation might be exerted via modulation of the late phase of neural glycoprotein synthesis. One-day-old chicks were used as experimental subjects. Incorporation of the radiolabelled glycoprotein precursor [3H]fucose into synaptic membranes of the chick forebrain was used as an index of glycoprotein fucosylation. Bilateral intracerebral injections of a corticosterone dose (0.5 micrograms/hemisphere) that facilitates long-term retention of weak learning were able to induce the late phase of glycoprotein synthesis in undisturbed chicks. A further experiment examined the effect of antibodies against the neural cell adhesion molecule on the facilitatory action of corticosterone on long-term memory for the weak passive avoidance training. Chicks trained on a weak aversant were injected with corticosterone (0.5 micrograms/hemisphere) 30 min post-training and testing occurred 24 h post-training. Administration of the neural cell adhesion molecule antibodies during the late phase (5.5 h post-training) blocked the facilitatory action of corticosterone on long-term memory. These findings further support the view that corticosteroids have a role in memory consolidation. In addition to previously proposed effects on gene transcription, these data suggest a post-translational glycosylation mechanism for the modulatory effect of corticosteroids on long-term memory formation.

Animals↗
PubMed1994

Corticosteroid receptor antagonists are amnestic for passive avoidance learning in day-old chicks.

Glucocorticoids can modulate behavioural processes and neural plasticity. They are released during learning situations and can trigger neural actions through binding to brain receptors. We hypothesized that a glucocorticoid action could play a critical role in the mechanisms involved in long-term memory formation. In order to test this hypothesis, chicks were trained on a passive avoidance learning task and given bilateral intracerebral injections of selective mineralocorticoid (RU-28318) or glucocorticoid (RU-38486) receptor antagonists. The results showed that both antagonists alter information processing when injected prior to the training session. Possible state-dependent effects were discharged. Further experiments evaluating possible effects of the antagonists on concomitant aspects of the learning situation (such as novelty reaction and pecking pattern) indicated that, as opposed to the glucocorticoid receptor antagonist, the mineralocorticoid antagonist altered the birds' reactivity to non-specific aspects of the training task. These results suggest that the two types of intracellular corticosteroid receptors could be mediating different aspects of the information processing and storage involved in avoidance learning. In addition, this study points out that passive avoidance learning in the chick could be a good model to investigate the biochemical mechanisms involved in corticosteroid actions on learning-induced neural plasticity.

Amnesia↗
PubMed1994

Corticosterone enhances long-term retention in one-day-old chicks trained in a weak passive avoidance learning paradigm.

Glucocorticoids are released during learning situations and can trigger neural actions through binding to receptors in different brain areas. The possible role of a glucocorticoid action in long-term memory formation was studied, in day-old chicks, by using a passive avoidance task which chicks otherwise only retain for a few hours (< 10) after training. Thus, we examined the effects of intracerebral corticosterone administration on retention 24 h posttraining. The results showed that chicks injected with corticosterone (1 microgram) at either 15 min pretraining or at 5, 30, 60 min (but not 120, 180, or 360 min) posttraining retained the passive avoidance response when tested 24 h posttraining. Studies with specific mineralocorticoid or glucocorticoid receptor antagonists (RU 28318 or RU 38486, respectively) indicated that this increase in retention by corticosterone might be mediated through glucocorticoid receptors. In order to assess whether the facilitatory effect of corticosterone was mediated through an effect on protein synthesis mechanisms, the protein synthesis inhibitor anisomycin was administered prior to corticosterone. However, this treatment only partially attenuated the effect of the steroid, suggesting that corticosterone may influence other cellular processes involved in the formation of long-term memory for the avoidance behaviour.

Animals↗
PubMed1993

Visual input and lateralization of brain function in learning in the chick.

Several lines of evidence (biochemical, neuroanatomical, electrophysiological, and behavioural) have indicated a critical role for the intermediate medial hyperstriatum ventrale of the chick forebrain in the acquisition of a passive avoidance response. Previous lesion studies indicated that bilateral or left, but not right, pretraining intermediate medial hyperstriatum ventrale lesions interfere with the acquisition of this task. We have further analysed this asymmetrical involvement of the intermediate medial hyperstriatum ventrale by use of a monocular learning protocol and intermediate medial hyperstriatum ventrale lesions (sham, bilateral, or unilateral). The results indicated that there is interocular transfer of information of passive avoidance learning between the two eye systems, with a tendency to be more successful from the right eye system to the left than in the opposite direction. As in binocular conditions, bilateral pretraining intermediate medial hyperstriatum ventrale lesions impair learning in monocularly trained animals. Unilateral lesions to either left or right monocularly trained experimental animals resulted in amnesia when they were made to the right intermediate medial hyperstriatum ventrale and the chicks were trained/tested with the left eye open. These results indicate that, although right intermediate medial hyperstriatum ventrale lesions do not result in amnesia in binocular animals, this region is capable of participating in memory acquisition processes. They also suggest a connection between lateralization of intermediate medial hyperstriatum ventrale function in passive avoidance learning and the behavioural and structural visual asymmetries known to occur in chicks.

Animals↗
PubMed1992

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness.

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.

Adrenocorticotropic Hormone↗