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R Jaffard

Publications and source records attributed to R Jaffard.

At least 37 records · Page 2Linked to original sources
PubMed1998

The specific dopamine uptake inhibitor GBR 12783 improves learning of inhibitory avoidance and increases hippocampal acetylcholine release.

The specific dopamine uptake inhibitor, GBR 12783 was tested on the retention performance of a one-trial passive avoidance test. For a moderate electric shock intensity, GBR 12783 (10 mg/kg), injected before acquisition session, improved retention performance. Scopolamine (0.125-0.5 mg/kg) completely blocked the promnesic effect of GBR 12783. Moreover, GBR 12783 increased hippocampal acetylcholine release in vivo. These data suggest that the promnesic effect of GBR 12783 is mediated by an increase in the septo-hippocampal cholinergic transmission.

Acetylcholine↗
PubMed1998

Opposite effects of lateral septal LTP and lateral septal lesions on contextual fear conditioning in mice.

The effect of fimbrial high-frequency stimulation (HFS)-induced long-term potentiation (LTP) in the lateral septum (LS) on contextual fear conditioning was studied in mice. Mice were conditioned for fear toward a novel context through the use of footshocks. The 1st experiment showed that pretraining HFS reduced significantly conditional freezing to contextual stimuli. The 2nd experiment was designed to determine whether the reduction of freezing produced by fimbrial HFS resulted from LTP in the LS rather than from LTP in other brain structures. Accordingly, mice with lesions of the LS were used and submitted to the same protocol as in the 1st experiment. Results showed that LS lesions completely abolished the impairing effect of fimbrial HFS and, as a whole, potentiated the freezing response. These data suggest that contextual fear conditioning is strongly modulated by the level of hippocampal-LS synaptic neurotransmission.

Analysis of Variance↗
PubMed1998

The opposite effects of cysteamine on the acquisition of two different tasks in mice are associated with bidirectional testing-induced changes in hippocampal adenylyl cyclase activity.

The hypothesis of a role for hippocampal somatostatin (SS-14) in learning and memory processes was further examined by means of 2 selective learning tasks that were previously shown to be either impaired (spatial discrimination task) or facilitated (barpressing task) by hippocampal lesions. Results showed that subcutaneous injections of cysteamine (160 mg/kg) (a) impaired acquisition of the spatial task while producing an opposite (i.e., facilitative) effect on acquisition of the barpressing task and (b) produced an up regulation of hippocampal adenylyl cyclase (AC) activity, which was antagonized by spatial discrimination training but enhanced by training in the barpressing task. Moreover, opposite task-dependent training-induced changes in hippocampal AC activity was observed in saline-treated mice. These results suggest that bidirectional regulatory mechanisms of hippocampal function involving both SS-14 and ACs may occur as a function of the type of learning.

Adenylyl Cyclases↗
PubMed1998

Footshock stress but not contextual fear conditioning induces long-term enhancement of auditory-evoked potentials in the basolateral amygdala of the freely behaving rat.

In this study, rats were bilaterally implanted with electrodes in the amygdala for chronic recording. Auditory click stimulation evoked in the basolateral nucleus a field potential characterized by three positive components: P1, P2 and P3 (peak latencies around: 10, 20 and 30 ms, respectively) which were each followed by three negative components: N1, N2 and N3 (peak latencies around: 13, 30 and 50 ms, respectively). Animals were divided into three groups (context-same, context-different and control). Following footshock administration, animals were either re-exposed to the same conditioning chamber (context-same group) or placed in a different context (context-different group) for electrophysiological and behavioural (evaluation of freezing response) recordings. The two early positive-negative complexes (P1-N1 and P2-N2) increased in amplitude from 2 min to 24 h following footshock in both context-same and context-different groups. No significant difference was observed between these two groups. The demonstration of significantly larger freezing responses in context-same subjects on exposure to the aversive conditioned environment indicated that this similarity of effects was not due to lack of conditioning of context under the experimental conditions chosen. We conclude that footshock stress produces general long-lasting changes in amygdala auditory field potentials that are not significantly affected by contextual fear conditioning.

Acoustic Stimulation↗
PubMed1998

Effects of chronic alcohol consumption or Diazepam administration on item recognition and temporal ordering in a spatial working memory task in mice.

This study was aimed at determining the effects of either Diazepam administration or chronic alcohol consumption (CAC) on spatial memory measured by concurrent discriminations in an eight arm radial maze using mice as subjects. Two different protocols involving a non-matching rule were used to evaluate either temporal order (recurrent items) or item recognition (non-recurrent items). Results showed that both Diazepam administration and CAC produced a memory deficit which was primarily observed in the temporal task, whereas item recognition was spared. These data show that Diazepam and CAC produced similar memory impairments. Thus, our study stressed the potential importance of the GABA/BDZ dysfunction in the production of organic amnesia of alcoholic origin. The overall analysis of the data suggests that both CAC and Diazepam injections would impair forms of memory sustained by automatic or incidental learning.

Aging↗
PubMed1997

Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids.

Aging is accompanied by troubles resulting from changes in hormonal and nutritional status. Therefore, the abundance of mRNA coding for triiodothyronine (TR) and retinoic acid (RA) nuclear receptors was studied in the brain of young, adult and aged (2.5, 6 and 24 months, respectively) rats. In the brain of aged rats, there was a lower abundance of TR and RAR mRNA and a lower activity of tissue transglutaminase (tTG), an enzyme the gene of which is a target for retinoids. Administration of RA in these rats restored TR and RAR mRNA and the activity of tTG in the brain. The importance of these observations to the function of the aged brain is discussed.

Age Factors↗
PubMed1997

Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment.

Ageing is accompanied by certain problems resulting from changes of hormonal status, in particular thyroid hormone (T3) status and vitamin A status. Since retinoic acid (RA), the active metabolite of vitamin A, and T3 play physiological roles in the adult brain, the effect of ageing on the amounts of mRNA for retinoic acid (RAR and RXR) and triiodothyronine (TR) nuclear receptors were studied. Also, the expression of RA and T3 target genes, tissue transglutaminase (tTG) and neurogranin (RC3), was measured in the whole brain and in the hippocampus of mice. Relative to young (3 months) mice, aged (22 months) mice exhibited lower amounts of RAR, RXR and TR mRNA concomitantly with a lower expression of tTG and RC3. RA administration to old mice (24 h before sacrifice) was able to restore the amount of mRNA of nuclear receptors and of RC3. It is hypothesized that a decrease in the cellular action of RA and T3 could play a role, via a decrease in the expression of RC3, in the alteration of synaptic plasticity occurring in aged mice.

Aging↗
PubMed1997

Contextual conditioned fear blocks the induction but not the maintenance of lateral septal LTP in behaving mice.

High-frequency stimulation (HFS) of the fimbria induces long-term potentiation (LTP) in the lateral septum. This study was aimed at investigating the effect of contextual fear conditioning on septal LTP with the use of behaving C57 BL/6 mice as subjects. For the acquisition of contextual fear conditioning, animals were placed in a conditioning chamber, where they were subjected to footshocks (FSs, 0.6 mA); the following day (retention), animals were reexposed to the chamber. Animals from the first group received HFS in their home cages before being submitted to conditioning; animals from the second group were first submitted to conditioning before receiving HFS during reexposure to the conditioning chamber; animals from the third group were submitted to the same regimen as those from the second group, except that no FS was delivered in the conditioning chamber; and animals from the fourth group received FS in the conditioning chamber but were maintained in their home cages the day after for LTP induction. Before conditioning, animals from the first group, placed in a familiar context (home cage), displayed an LTP of the N3 wave of septal field potential. After conditioning, reexposure of these animals to the conditioning chamber produced a transient decrease in the amplitude of N3 but did not interfere with the duration of maintenance of LTP. Conversely, in animals from the second group, when HFS was applied during reexposure to the conditioning chamber the induction of LTP was totally blocked. However, mice from the two other groups (3rd and 4th) displayed normal levels of LTP. Taken together with previous findings, these data suggest that contextual conditioned fear may interfere with certain forms of learning via blockade of hippocampal-septal LTP.

Animals↗
PubMed1997

S 15535, a novel benzodioxopiperazine ligand of serotonin (5-HT)1A receptors: II. Modulation of hippocampal serotonin release in relation to potential anxiolytic properties.

In these studies, we characterized the influence of the novel benzodioxopiperazine serotonin (5-HT)1A ligand, S 15535, on the release of 5-HT in rat hippocampus and compared its potential anxiolytic properties with those of the 5-HT1A receptor partial agonist, buspirone, the 5-HT1A antagonist, WAY 100,635 and the benzodiazepine, diazepam (DZM). (Doses are in milligrams per kilogram s.c., unless otherwise specified.) S 15535 dose-dependently (0.3-3.0) reduced dialysate concentrations of 5-HT in the hippocampus of anesthetized rats. This action of S 15535 (3.0) was blocked by WAY 100,635 (0.3), (-)-penbutolol (2.0) and (-)-tertatolol (8.0), antagonists at 5-HT1A autoreceptors. In rats, fear-induced ultrasonic vocalizations (USVs) were dose-dependently abolished by S 15535 (0.16-2.5 s.c. and 0.63-10.0 p.o.), an action mimicked by buspirone (0.02-2.5) and DZM (0.16-10.0). Further, the action of S 15535 (0.63) was abolished by WAY 100,635 (0.16) and (-)-penbutolol (10.0), which were inactive alone. S 15535 dose-dependently (0.63-10.0 s.c. and 2.5-40.0 p.o.) blocked aggressive encounters in isolated mice; buspirone (0.16-10.0) and, at high doses, DZM (2.5-40.0) were also effective. WAY 100,635 (0.16), which was inactive alone, fully antagonized the antiaggressive actions of S 15535 (2.5). In an elevated plus-maze, neither S 15535 (0.0025-10.0), buspirone (0.0025-10.0) nor WAY 100,635 (0.00063-0.63) significantly increased open-arm entries, whereas they were increased by DZM (0.16-0.63). In the pigeon conflict test, S 15535 (0.04-0.16 i.m.) markedly increased punished responses and only slightly decreased unpunished responses, even at a 64-fold higher dose. In contrast, buspirone (0.16-2.5 i.m.) and DZM (0.04-2.5 i.m.) showed no or a less marked (4-fold) separation between doses increasing punished and decreasing unpunished responses. In the presence of the 5-HT1A antagonist, (-)-alprenolol (10.0 mg/kg i.m.), S 15535 did not increase punished responses. In a Geller conflict paradigm in rats, S 15535 dose dependently (0.3-3.0) increased punished responses, and its action (1.0) was blocked by (-)-penbutolol (8.0). S 15535 (0.63-40.0 s.c. and 2.5-40.0 p.o.) exerted little influence on motor behavior. In conclusion, in line with its net inhibition of serotoninergic transmission by activation of 5-HT1A autoreceptors and blockade of postsynaptic 5-HT1A receptors, S 15535 expresses anxiolytic activity. In addition, it displays antiaggressive (and antidepressant, accompanying paper) properties. Further, S 15535 does not compromise motor behavior at doses over which it expresses its anxiolytic properties. Thus, S 15535 represents a promising candidate for the treatment of anxious states in man.

Aggression↗
PubMed1996

Chronic ethanol consumption increases the amount of mRNA for retinoic acid and triiodothyronine receptors in mouse brain.

It is known that alcohol induces disorders in the metabolism of retinoids and particularly in the biosynthetic pathways of retinoic acid (RA). Since RA has, along with other hormones and particularly triiodothyronine (T3), a physiological role in the adult brain, the effect of chronic exposure to alcohol on RA and T3 status was investigated. The amounts of RA receptor (RAR) and T3 receptor (TR) mRNAs were quantified and the activity of the 'tissue' transglutaminase (tTG; an RA-dependent enzyme) was assayed in the brain of mice following chronic ethanol consumption (CEC; 12% v/v for 6-10 months). Compared to controls, ethanol-treated mice exhibited increased amounts of RAR and TR mRNAs together with an increase in tTG activity. It is hypothesized that the enhanced cellular action of RA and T3 could play a role in the previously described brain damages induced by CEC.

Alcoholism↗
PubMed1996

Investigations on the role of hippocampal protein kinase C on memory processes: pharmacological approach.

We report here investigations on the functional involvement of hippocampal protein kinase C (PKC) in learning and long-term retention of spatial discrimination in a radial maze. A pharmacological approach was employed to test the behavioural effects of intrahippocampal injections of drugs that either activate or inhibit PKC activity. Mice with intrahippocampal guide cannula were trained in a mixed spatial reference-working memory task during 7 daily sessions. Sixteen days later, the animals were submitted to a retention session. In the first experiment, the animals were treated before each learning session with polymyxin B (PMB, a PKC inhibitor) and their scores were compared to those of an appropriate control group. In the second experiment, a group received the injection of 1-oleoyl-2-acetyl glycerol (OAG, a PKC activator) before and after the 7th learning session in order to test the effect of activation of PKC on long-term retention. The results showed that: (1) PMB administration delayed the acquisition of the reference memory component of the task, whereas long-term retention appeared to be improved; and (2) administration of OAG at the end of the acquisition phase improved long-term retention. Neither PMB nor OAG appeared to affect working memory. Taken together, the results point to an involvement of hippocampal PKC in the acquisition of information destined for long-term storage.

Animals↗
PubMed1996

Reduction of regional brain glucose metabolism following different durations of chronic ethanol consumption in mice: a selective effect on diencephalic structures.

The effects of chronic alcohol consumption on regional brain glucose metabolism were examined in Balb/c mice using the [14C]2-deoxyglucose autoradiographic technique. Animals were given a solution of 12% v/v ethanol as their only source of fluid for either 6, 12 or 18 months and compared to control groups receiving either an isocaloric solution or saccharose or tap water. Alterations of cerebral brain glucose metabolism were assessed in mice who were returned to a non-alcoholic diet and allowed to freely explore a T-maze. The results showed that chronic ethanol consumption induced reductions of regional metabolic activity which were functions both of the duration of alcohol treatment and of the structure studied. Whereas a six month period of alcoholization did not induce any significant effects on metabolic activity, 12 months of treatment were necessary to induce the first observable and significant reductions in [14C]2-deoxyglucose labelling. These effects were mainly limited to diencephalic structures such as the lateral mammillary nuclei and the anterodorsal thalamic nuclei. The cerebellum was also affected but to a lesser degree. After 18 months of alcoholization, a generalized spread of the metabolic reduction to the entire mammillary complex (lateral, medial and posterior nuclei) and to the thalamic nuclei was observed. This same duration of treatment was necessary to induce the first detectable decrease of metabolic activity in the hippocampus. In agreement with data from human neuropathology, these findings confirm the particular vulnerability of diencephalic structures to ethanol and suggest that damage limited to diencephalic regions rather than to hippocampal or cortical areas could be primarily responsible for the memory disorders observed in Korsakoff's syndrome.

Alcohol Drinking↗
PubMed1996

Effects of methyl beta-carboline-3-carboxylate on memory impairments induced by chronic alcohol consumption in mice.

1. The effects of systemic administration of beta CCMon the memory impairments induced by chronic alcohol consumption in a delayed alternation task were studied. 2. For this purpose, Balb/c mice were submitted to chronic alcohol treatment during 12 months and were subsequently withdrawn from the alcoholic diet at least four weeks before behavioral testing began. 3. Results showed that alcohol-treated animals exhibited a delayed alternation deficit that was totally reversed by the administration of beta CCM administered before the retention trial only. 4. These findings show that the memory deficits observed in alcohol-treated animals are due to an impairment of the retrieval phase of memory processes, and that retrieval memory processes are sensitive to benzodiazepine receptor ligands.

Animals↗
PubMed1996

Differential temporal evolution of post-training changes in regional brain glucose metabolism induced by repeated spatial discrimination training in mice: visualization of the memory consolidation process?

The present study analyses the effects of the stage of learning on the spatial patterns and time-course of [14C]glucose uptake in BALB/c mice brain regions produced by spatial discrimination training in an eight-arm radial maze. Our particular approach was designed to follow, during the post-training period, the level of functional activity in individual brain areas which may underlie the memory consolidation process. Regional mapping of relative [14C]glucose uptake was assessed at three post-training time intervals (5 min, 1 and 3 h) after either the first (Day 1), the fourth (Day 4) or the last (Day 9) daily training session of the discrimination task and compared with sham-conditioned animals placed in the same experimental environment. The results indicated that numerous subcortical and cortical brain regions exhibit metabolic alterations following the acquisition of the spatial discrimination task. These alterations, which were specifically related to learning since they did not appear in sham-conditioned animals, were functions both of the post-training interval studied and of the degree of mastery of the task. On Day 1, a progressive, time-dependent and sequential increase in labelling was found from subcortical (5 min post-training) to cortical regions (3 h post-training). On Day 4, a peak of cortical metabolic activation was identified at 1 h post-training. In contrast, on Day 9, maximum labelling was found 5 min post-training in all subcortical and cortical regions followed by a general monotonic decline at 1 and 3 h post-training. These findings, which show widely distributed changes of metabolic activity in the brain, are consistent with the hypothesis that learning involves distributed neural networks. The sequential activation from subcortical to cortical regions seems to indicate a general mechanism whose function would ultimately be to store cortical memory representations. The acquisition-dependent shifts in the patterns of post-training metabolic labelling observed as a function of task mastery may be taken to represent a visualization of the spatio-temporal evolution of the networks of brain structures actively engaged in the memory consolidation process. In particular, the present data suggest that the duration of post-acquisition memory processing is a function of the quantity of new information which has to be dealt with by the central nervous system.

Animals↗
PubMed1996

Changes in synaptic excitability in the lateral septum associated with contextual and auditory fear conditioning in mice.

Synaptic excitability in the lateral septum (LS) was assessed electrophysiologically in freely moving mice either submitted to a painful stimulus (shock) or tested on two forms of conditioned fear: contextual conditioning and auditory cue conditioning. Only the amplitude of the N3 component of the two negative waves (N2 and N3) evoked by fimbrial stimulation displayed significant changes in these tests. Experiment 1 showed that both the painful stimulus and subsequent re-exposure (24 h later) to the conditioning foreground context induced significant and context specific decrease in the N3 amplitude. In Experiment 2, a phasic tone (conditioned stimulus: CS) was paired (paired group) with the footshock (unconditioned stimulus: US) or not (unpaired group) and, 24 h later, animals were re-exposed successively to the auditory cue and to the context. During the auditory cue test, only the paired group displayed significant freezing and this occurred only during presentation of the CS. In this group, however, a significant reduction in the N3 amplitude was only observed immediately after the cessation of the CS. During the context test, the percentage and time-course of freezing across the 10 mm session were similar in each group. However, in the unpaired group the N3 amplitude reduction was significant and outlasted the duration of the freezing behaviour itself. These results show that alterations in LS synaptic excitability may be dissociated from fear-induced freezing behaviour. We suggest that LS synapses are part of a brain circuit that predict if and when the US is going to occur.

Acoustic Stimulation↗
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

Alteration of cortical and hippocampal cholinergic activities following lesion of the mammillary bodies in mice.

The effects of ibotenic acid lesions of the mammillary bodies (MM) on the sodium-dependent high affinity choline uptake (SDHACU) velocity into both the hippocampus and the frontal cortex were investigated in this study in either a quiet or an active (exploration of a T-maze) condition. Results showed that MM lesion globally produced a significant decrease of both hippocampal and cortical SDHACU. However, the magnitude of this decrease was not significantly different in the active as compared to the quiet condition. These findings suggest that MM lesion alters the tonically but not phasically active transynaptic control of cortical and hippocampal cholinergic activities.

Acetylcholine↗