Biomedical subjects

C Messier

Publications and source records attributed to C Messier.

At least 37 records · Page 2Linked to original sources

PubMed1997

Object recognition in mice: improvement of memory by glucose.

In most of the demonstrations of the memory-improving action of glucose in animals, training conditions have included electric shocks, food deprivation, or food rewards, all of which produce changes in blood glucose. In these experiments, training conditions may interact with the exogenous injection of glucose and make it more difficult to interpret results. To circumvent this problem, the ability of glucose to improve memory in an object-recognition task was examined. Animals were first habituated to an open field. The next day, they were placed in the same open field together with two identical objects and the time spent observing and exploring the objects was recorded. The animals were then given either a saline or an immediate or delayed (1 and 5 h) glucose (500 mg/kg) injection or no treatment. On the final day, animals were placed in the open field with a previously observed object and a new object. Exploration time was recorded. Results showed that the animals that received the immediate glucose injection spent significantly more time exploring the new object, suggesting that glucose retroactively and noncontingently improved the memory for the previously observed object.

Animals↗

PubMed1997

An automatic food delivery system for operant training of mice.

We describe an adjustable food delivery system that cuts and delivers calibrated pieces of spaghetti to be used as reinforcers to train mice in an appetitive bar-pressing task. The food delivery is computer-controlled. Uneaten reinforcers are detected and removed automatically. One main advantage of this system is the ability to adjust reinforcer size to as small as 3 mg. A second advantage is that small reinforcers effectively prevent the rapid satiation usually observed with commercial products designed for rats, and allow for the expression of high behavioral output. Finally, the use of these dustless reinforcers drastically reduces the incidence of blockage, a common occurrence with commercial products using pellets.

Animals↗

PubMed1997

Blockade of spontaneous posttraining performance improvement in mice by NMDA antagonists.

We investigated the effects of immediate post-training systemic administration of gamma-L-glutamyl-L-aspartate (gamma-LGLA) and 3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (CPP), antagonists at the N-methyl-D-aspartate receptor, in a lever-press task in two inbred strains of mice. When retention performance was tested in control animals 24 h after partial acquisition of the task. BALB/c mice exhibited a spontaneous performance improvement whereas C57BL/6J mice did not gamma-LGLA at doses of 2.5 and 25 mumol/kg and CPP at doses ranging between 0.025 and 2.5 mumol/kg blocked the spontaneous performance improvement found in BALB/c mice but had no apparent effects on the retention performance of C57BL/6J mice. These data suggest that retention impairment induced by CPP and gamma-LGLA in BALB/c mice results from an interference with posttraining memory processes.

Animals↗

PubMed1996

Glucose regulation and cognitive functions: relation to Alzheimer's disease and diabetes.

Glucose has been found to improve memory in animals and humans. Animal research has revealed that glucose may improve memory through a facilitation of acetylcholine (ACh) synthesis and release in the brain. This glucose-related memory improvement has prompted research in elderly humans. These studies have shown that the memory-improving action of glucose depends on each individuals' blood glucose regulation. Based on these data, researchers have evaluated the effect of glucose on memory in patients with Alzheimer's disease (AD). Results demonstrated that glucose could improve memory in a subset of patients that had abnormalities in their blood glucose regulation. Interestingly, these alterations in blood glucose regulation were believed to depend on the severity of the disease process. Another line of investigation has focused on alterations in brain glucose metabolism. Both animal models and studies with Type II diabetic elderly patients have shown that altered glucose regulation impairs learning and memory processes. It is possible that in AD patients, hyperglycemia exerts a deleterious effect by potentiating the neuronal death produced by other pathological processes taking place such as amyloid deposition. Based on these data, it appears important to find the prevalence of altered glucoregulation at various stages of AD. Secondly, it may be of interest to determine prospectively whether altered glucoregulation is linked to a faster progression of the disease. Finally, if such a relationship is observed, the next logical step would be to determine whether AD patients could benefit from treatments aimed at normalizing blood glucose regulation and improving insulin sensitivity.

Alzheimer Disease↗

PubMed1995

Glucose enhancement of scopolamine-induced increase of hippocampal high-affinity choline uptake in mice: relation to plasma glucose levels.

The administration of glucose has been shown to improve memory for various learning tasks in rodents. In humans, glucose also increases declarative memory performance in elderly people and in some patients with mild Alzheimer's disease. One of the possible physiological bases for the effect of glucose on memory processes is a facilitation of cholinergic function through increased synthesis. In support of this hypothesis, glucose was shown to attenuate the amnesia induced by scopolamine and, in similar conditions, glucose increased extracellular levels of acetylcholine following a scopolamine injection. To further examine the interaction between glucose and cholinergic function, the present experiment measured the effects of combined injections of glucose and scopolamine on hippocampal sodium-dependent high-affinity choline uptake, an indirect index of cholinergic activity. Results showed that the injection of 3 g/kg glucose enhanced the increase in high affinity choline uptake in hippocampal synaptosomes produced by scopolamine. A regression analysis revealed the existence of a positive correlation between plasma blood glucose level and hippocampal choline uptake particularly in the animals receiving a combined injection of scopolamine and glucose. These data further support the hypothesis that glucose administration can facilitate acetylcholine synthesis under certain conditions and that this action could explain how glucose attenuates scopolamine-induced amnesia.

Analysis of Variance↗

PubMed1995

Repeated blood glucose measures using a novel portable glucose meter.

We describe the use of a novel portable blood glucose meter to repetitively and rapidly measure blood glucose levels in mice. We used this apparatus to replicate in the mouse, an insulin tolerance test (ITT) developed for humans. This test involves repeated glucose sampling (0, 1, 3, 5, 7, 10, 15, and 20 min) after an IV bolus of 0.4 IU/Kg of insulin. We first ran comparative tests with a conventional automated glucose analyser to assess the precision and reliability of the blood glucose meter for use in the mouse. High correlation were found between the two measures using either capillary or trunk whole blood. The variability of measurement over five consecutive determinations was about 3%. It was possible to take repetitive measures at about 70 s intervals.

Adult↗

PubMed1993

Memory processing and apamin induce immediate early gene expression in mouse brain.

The present study analyses the effects of learning on the spatial pattern and the time-course of changes of immediate early gene messenger RNA's (c-fos and c-jun) in mouse brain produced by training in an appetitive bar-pressing task. Activation of c-fos and c-jun after training is strictly located in the hippocampal formation and is learning-dependent. Levels of both proto-oncogene mRNAs in the trained group were 4 to 5 times higher than in the sham-conditioned group. Injections of apamin, a bee venom neurotoxin that selectively blocks a class of Ca(2+)-activated K+ channels and improves learning and memory retention, produced as compared to untrained animals a 3- to 5-fold increase of expression of c-fos and c-jun with the same pattern as that observed in the trained animals. Post-training injection of 0.2 mg/kg apamin enhanced 1.4-fold the expression of both immediate early genes in CA1, CA3 and dentate gyrus as compared to trained saline-injected mice. All these results suggest that apamin-induced increase of immediate early gene expression might be related to the apamin-induced facilitation of learning.

Animals↗

PubMed1992

Raised glucose levels enhance scopolamine-induced acetylcholine overflow from the hippocampus: an in vivo microdialysis study in the rat.

Behavioural studies in both humans and animals have shown that an acute rise in circulating glucose levels at or around the time of training enhances subsequent retention performance and can also afford protection from the amnesia produced by posttraining injections of scopolamine. In an attempt to directly investigate the neurochemical basis for these effects of glucose we have tested the hypothesis that raised glucose levels may enhance acetylcholine (ACh) synthesis and release in the brain during conditions of increased neuronal activity, induced either by training or pharmacological challenge, via a microdialysis study using rats. Microdialysate concentrations of ACh overflow from the hippocampus of fasted rats induced by i.p. injections of scopolamine (1 mg/kg) combined with concurrent s.c. injections of either glucose (2 g/kg) or saline were compared in successive 15-min samples using an on-line HPLC system. Scopolamine injections resulted in an immediate 10-20-fold increase in hippocampal ACh overflow which subsequently progressively declined over a 4-h period to pretreatment baseline levels. The combined injection of glucose with scopolamine resulted in a highly significant enhancement (19.4%; P less than 0.01) in ACh content of the first two samples as compared to saline-injected controls. These results provide the first direct experimental evidence that raised glucose levels, via increased availability of acetyl-coenzyme A (acetyl-coA), transiently facilitates ACh synthesis and release during conditions of increased neuronal activity. This enhancement of ACh availability during states of cholinergic neuronal activation may underlie the previously observed facilitatory effects of glucose on memory performance and its protection from scopolamine-induced amnesia.

Acetylcholine↗

PubMed1992

Locomotor bias produced by intra-accumbens injection of dopamine agonists and antagonists.

Several experiments have shown that the dopamine (DA) receptors in the nucleus accumbens control the intensity of locomotor activity; however, there are several contradictory results concerning the role of the accumbens in the regulation of the direction of locomotion. To further evaluate the contribution of dopaminergic function in the accumbens to the direction of locomotion, we first compared the effect on the direction of locomotor activity of unilateral intra-accumbens injections of the nonspecific DA antagonist haloperidol, the specific D-1 antagonist SCH-23390, the specific D-2 antagonist metoclopramide. In the second part of the experiment, we examined the effect on the direction of locomotor activity of unilateral intra-accumbens injections of the non-specific DA agonist apomorphine, the specific D-1 agonist SKF-38393, the specific D-2 agonist LY-171555, and the combination of SKF-38393 and LY-171555. Haloperidol, metoclopramide and to a lesser extent, SCH-23393 together with peripheral amphetamine injections produced a locomotor bias that resulted in ipsilateral turning. Apomorphine, LY-171555 or the combination of SKF-38393 and LY-171555 (but not SKF-38393 alone) produced a locomotor bias that resulted in contralateral turning. No significant locomotor bias was produced by intra-accumbens injection of the various vehicles. These results suggest that the bilateral DA organization thought to exist in the nigro-striatal pathway for the control of locomotion may also be true for the mesolimbic dopamine system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1991

Effect of apamin, a toxin that inhibits Ca(2+)-dependent K+ channels, on learning and memory processes.

Apamin, a neurotoxin extracted from bee venom, specifically binds to a particular class of Ca(2+)-activated K+ channels which are involved in the slow afterhyperpolarization (S-AHP) that follows action potentials in many excitable cells. We tested in mice the effects of apamin on learning and memory processes. The results showed that pre-training injection of apamin accelerated the acquisition of a bar-pressing response but also increased the bar-pressing rates of the animals. This latter result suggests that apamin accelerated acquisition because it increased behavioral activity in general and the number of bar-presses in particular. Post-training apamin injection retroactively and non-contingently facilitated memory processes taking place shortly after training in a bar-pressing task. The lack of an effect of the delayed apamin injection showed that apamin did not act proactively on memory retrieval processes. These results suggest that apamin-sensitive KCa channels may contribute to memory processes.

Animals↗

PubMed1991

Bidirectional potentiation between D1 and D2 dopamine agonists: effects of unilateral intra-accumbens injections on locomotor activity in mice.

We tested the effect of a single unilateral injection of a specific D1 agonist into the nucleus accumbens on the behavioral response to a subsequent unilateral intra-accumbens injection of a selective D2 agonist ten days later. The effect of the inverse order of presentation (D2 agonist followed ten days later by a D1 agonist) was also tested. No significant differences between the locomotor effects of the intra-accumbens injection of either SKF-38393 (3.5 micrograms) or LY-171555 (10 micrograms) were observed during the first test. Ten days later, during the second test, intra-accumbens injection of either the LY-171555 and SKF-38393 increased the percentage of contralateral rotations relative to the first test while LY-171555 also increased the total number of rotations. Control injections showed that these effects of LY-171555 and SKF-38393 were not due to a conditioning process. Rather, the results suggested that the locomotor changes observed during the second test were the result of behavioral sensitization due to the initial acute injection of the agonists.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1991

Time-dependent sequential increases in [14C]2-deoxyglucose uptake in subcortical and cortical structures during memory consolidation of an operant training in mice.

Previous results have suggested that memory processing may involve the sequential activation of subcortical and cortical structures. To study this phenomenon, we have examined the immediate (15 min) and delayed (220 min) metabolic changes produced in BALB/c mice by a partial training session in a bar-pressing appetitive task, using the [14C]-2-deoxyglucose (2-DG) relative glucose uptake method. These relative metabolic changes were compared to the ones produced in several control groups: untrained animals, sham-conditioned animals, overtrained animals, and animals forced to walk on a moving belt (immediate and delayed condition). Animals were given a single intrajugular injection (5 microCi) of 2-DG either 5 min before or 3 h (delayed condition) after the second training session. Forty minutes after the 2-DG injection, the animals were sacrificed and their brains processed for autoradiography. At the 15-min delay, a large 2-DG labeling increase was found in partially trained animals for various subcortical areas (septum, diagonal band, hippocampus, thalamus, and mammillary bodies) while a much smaller increase was found in four cortical areas (frontal, cingulate, parietal, and sensory motor cortices). At the 220-min delay, we observed a large 2-DG labeling increase in cortical (frontal, pyriform, and cingulate cortices) and subicular areas while a moderate 2-DG labeling increase was observed in entorhinal cortex and the diagonal band. These results show that, shortly after training, subcortical structures are preferentially activated while cortical structures are much less activated. Three hours later, at a time when retention performances have been shown to improve spontaneously in the same strain of mice and in the same task, cortical structures are highly activated.

Animals↗

PubMed1991

Polyclonal anti-idiotypic antibodies as internal images of dopamine. Applications for biochemical and morphological studies of DA receptors in the rat brain.

Polyclonal anti-idiotypic antiserum raised against both rabbit and monoclonal anti-dopamine (DA) antibodies was produced in rabbits. It was characterized for its specificity and was shown to (1) inhibit the binding of both polyclonal and monoclonal idiotypic anti-DA antibodies directed to immobilized DA conjugates; (2) inhibit the binding of (3H) DA to rat brain membranes; (3) to cross-react with a peptide extracted from a neuroblastoma cell line (NCB-20), known to express functional DA receptors. Finally, immunocytochemical studies were performed on paraformaldehyde-fixed rat brain. Anti-idiotypic antibodies were used to visualize the cellular and subcellular distribution of DA receptor binding sites in the striatum, a region that contains both D1 and D2 receptors subtypes. Under the electron microscope, the immune reaction product was observed to be concentrated in postsynaptic sites belonging mainly to dendritic spines, while presynaptic structures were sparsely labeled.

Animals↗

PubMed1991

Locomotor bias produced by intra-accumbens and intracaudate injection of polyclonal dopamine anti-idiotypic antibodies.

The preceding article described anti-idiotypic antibodies to conjugated dopamine (AIDA); results were consistent with the hypothesis that these antibodies contained the internal image of conjugated dopamine (DA-G-BSA) and binded to dopamine (DA) receptors. We further tested these anti-idiotypic antibodies to conjugated dopamine by examining the functional changes produced by unilateral injection of AIDA (or DA-G-BSA) into the nucleus accumbens or into the medio-dorsal caudate in mice. Our results showed that unilateral injection of AIDA (or DA-G-BSA) into the nucleus accumbens or into the medio-dorsal caudate produced an ipsilateral locomotor asymmetry in amphetamine-treated animals which was similar to the one produced by unilateral intra-caudate injection of haloperidol (a non-specific DA antagonist). The asymmetry was site specific: injection of AIDA around the nucleus accumbens or into the anterior caudate was not effective. The asymmetry was also shown not to depend on the peripheral injection of amphetamine. Taken together, the present results and those in the preceding article suggest that the AIDA contains the internal image of DA-G-BSA and that these two substances bind to DA receptors to produce behavioral changes.

Animals↗

PubMed1990

Memory-improving action of glucose: indirect evidence for a facilitation of hippocampal acetylcholine synthesis.

The effect of a 3 g/kg glucose injection on the velocity of the sodium-dependent high-affinity choline uptake mechanism in the hippocampus was both measured in quiet control mice and in mice immediately after training in an operant bar pressing task. Glucose did not significantly change high-affinity choline uptake in resting animals. High-affinity choline uptake in the hippocampus was increased by training in the operant bar pressing task. Glucose significantly reduced the amplitude of the increase in high-affinity choline uptake observed in the trained animals. Similarly, a 3 g/kg glucose injection also attenuated the increase in high-affinity choline uptake observed in animals injected with 1 mg/kg scopolamine. Finally, a 3 g/kg glucose injection significantly attenuated the amnesia produced by a post-training 1 mg/kg scopolamine injection in mice trained for an operant bar pressing task. These results provide additional evidence for an action of glucose on hippocampal cholinergic activity under conditions of high acetylcholine demand. This action may be mediated via an increase in acetyl coenzyme A availability, one of the precursors of acetylcholine. This facilitative effect of glucose on hippocampal acetylcholine synthesis may constitute the physiological basis for its facilitative action on memory and its attenuation of scopolamine amnesia.

Acetylcholine↗

PubMed1989

Quantitative [14C]2-deoxyglucose study of a functional dissociation between anterior and posterior cingulate cortices in mice.

We have previously shown that lesion of the posterior cingulate cortex (CCP) but not of the anterior cingulate cortex (CCA), produced learning and memory deficits. As a first evaluation of the functional anatomical basis of this dissociation, we used the quantitative [14C]2-deoxyglucose method and electrical brain stimulation to determine the functional connections of the CCA and CCP in mice. CCP stimulation (but not CCA stimulation) produced significant metabolic increases in the hippocampal formation and in the subicular complex. This result is consistent with the hypothesis that learning and memory deficits following CCP lesion may be due to the disruption of functional neural pathways between the CCP and hippocampal structures.

Animals↗

PubMed1989

[Circling behavior produced by the unilateral intra-accumbens injection of dopaminergic agonist and two dopaminergic antagonists in mice].

Unilateral intra-accumbens injection of apomorphine, a dopaminergic agonist, produced circling contralateral to the site of injection in Balb/c mice. Unilateral intra-accumbens injection of haloperidol and metoclopramide, two dopaminergic antagonists, produced ipsilateral circling. These results support the hypothesis that the dopaminergic receptors in the nucleus accumbens also contribute to the direction of locomotor activity.

Animals↗

PubMed1988

Improvement of memory for an operant response by post-training glucose in mice.

Previous experiments have shown that a post-training glucose injection can retroactively and non-contingently improve the retention of a previously learned association. To date, the memory-improving action of glucose has only been demonstrated in rats for negatively-motivated tasks. The present experiment sought to generalize these previous results by examining the effects in mice of post-training glucose injections on the retention of an operant bar-pressing response. The results show that post-training glucose can retroactively and non-contingently improve the retention of an appetitively motivated task in mice. There was a U-shaped relationship between the dose of glucose and the effect on memory similar to the ones already observed in rats using negatively motivated training. The implications of these results for an endogenous memory modulation mechanism are discussed.

Animals↗