Biomedical subjects

I Léna

Publications and source records attributed to I Léna.

7 recordsLinked to original sources

PubMed2005

Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep--wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats.

We used intracerebral microdialysis coupled with electrophysiologic recordings to determine relative changes in the concentrations of several neurotransmitters in the medial prefrontal cortex and nucleus accumbens of freely moving rats during waking, slow-wave sleep, and rapid eye movement (REM) sleep. The concentrations of noradrenaline, dopamine, glutamate, and aspartate in 2-min dialysate samples were analyzed by capillary electrophoresis combined with laser-induced fluorescence detection. Changes in glutamate and aspartate concentrations were found only in the nucleus accumbens, in which a decrease was obtained during both slow-wave sleep and REM sleep compared to waking. A progressive reduction in the release of noradrenaline was observed from waking to REM sleep in both structures. In contrast, dopamine concentrations were higher during waking and REM sleep compared to that during slow-wave sleep. The latter results demonstrate that contrary to the findings of earlier electrophysiologic studies carried out on ventral tegmental area dopaminergic neurons, changes in the release of dopamine in projection areas occur across the sleep-wake cycle. The elevated levels of dopamine during waking and REM sleep in the medial prefrontal cortex and the nucleus accumbens could result from changes during these two states in afferent modulation at the level of cell bodies or at the level of dopaminergic terminals.

Animals↗

PubMed2001

Involvement of D2 dopamine receptors in the opposing effects of two CCK-B agonists in a spatial recognition memory task: role of the anterior nucleus accumbens.

RATIONALE: A previous study in the rat has shown that systemic injection of two CCK-B agonists, BC264 and BC197, induced opposing effects on the retrieval phase of a spatial recognition memory task. OBJECTIVE: The present study was designed to investigate the mechanisms underlying these effects at the level of the dopaminergic system. METHODS: Rats were injected IPly with BC264 (0.3 microg/kg) or BC197 (30 microg/kg) and with D1 or D2 agonists and antagonists. The cognitive performances of rat were analysed on the retrieval phase of a spatial recognition memory task. The extracellular levels of dopamine were quantified in the anterior nucleus accumbens after injection of BC197 (3, 30 and 300 microg/kg IP), using the microdialysis technique on freely moving rats. Local injection of the D2 antagonist, sulpiride (2.5 ng/microl) was performed in the anterior nucleus accumbens and the cognitive performances analysed following systemic injection of BC264 (0.3 microg/kg). RESULTS: The improvement and the impairment of performance induced respectively by BC264 and BC197 were suppressed by peripheral administration of sulpiride, showing that these opposing effects were both mediated by the stimulation of D2-like receptors. However, different dopaminergic pathways seem to be involved in the effects of the two CCK-B agonists. Indeed, systemic administration of BC197 did not induce the increase of extracellular dopamine levels observed with BC264. Furthermore, local injection of sulpiride, in the anterior nucleus accumbens, completely suppressed the cognitive enhancing effect of BC264. CONCLUSION: These findings suggest that the D2-mediated deficit in the performance induced by BC197 involves brain structures other than the anterior nucleus accumbens. They also demonstrate a critical role of dopaminergic transmission within the anterior nucleus accumbens in the improving effect induced by BC264 in a spatial memory task.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Rat hippocampal neurons are critically involved in physiological improvement of memory processes induced by cholecystokinin-B receptor stimulation.

The involvement in memory processes of the neuropeptide cholecystokinin (CCK) through its interaction with the CCK-B receptors was studied. The two-trial recognition memory task was used. Control animals showed recognition memory after a 2 hr time interval but not after a 6 hr time interval between the two trials. The improving effect of a selective CCK-B agonist, BC 264, intraperitoneally administered (0.3 microgram/kg) in the retrieval phase of the task (6 hr time interval), was also observed after its injection (1 pmol/0.5 microliter) in the dorsal subiculum/CA1 of the hippocampus but not in the caudate/putamen nucleus or in the prefrontal cortex of rats. The CCK-B antagonist L-365,260 injected (10 ng/0.5 microliter) into this region of the hippocampus abolished the improving effect of BC 264 injected intraperitoneally. Furthermore, L-365,260 injected in the hippocampus suppressed the recognition of the novel arm normally found in the controls (2 hr time interval) when it was injected before the acquisition or the retrieval phase of the task. In addition, an increase of the extracellular levels of CCK-like immunoreactivity in the hippocampus of rats during the acquisition and retention phase of the task was observed. Finally, CCK-B receptor-deficient mice have an impairment of performance in the memory task (2 hr time interval). Together, these results support the physiological involvement of the CCKergic system through its interaction with CCK-B receptors in the hippocampus to improve performance of rodents in the spatial recognition memory test.

Animals↗

PubMed1999

Cognitive enhancing effects in young and old rats of pBC264, a selective CCK(B) receptor agonist.

RATIONALE: The implication of CCK(B) receptors in cognitive processes is far from fully understood. OBJECTIVE: The present study investigated the effect of propionyl-BC264, a selective agonist of CCK(B) receptors, in young and old rats. METHODS: Cognitive functions were studied in a two-trial recognition memory task developed in our laboratory. RESULTS: It was shown that propionyl-BC264 enhanced information processing in young as well as in old rats when injected (10 microg/kg; IP) immediately after the acquisition phase and before the retrieval trial but not before the acquisition trial. This cognitive enhancing effect was blocked by prior administration of L 365,260, a selective CCK(B) receptor antagonist. CONCLUSIONS: In view of the fact that BC264 is devoid of anxiogenic effects, it could be of value in the treatment of cognitive impairments associated with both normal and pathological ageing.

Aging↗

PubMed1999

Opposing effects of two CCK(B) agonists on the retrieval phase of a two-trial memory task after systemic injection in the rat.

The effects of two selective CCK(B) agonists, BC 264 and BC 197, on memory processes were investigated in rats using a recently developed two-trial recognition memory task. Control animals showed recognition memory after a 2 but not a 6 h time interval between the two trials, thus allowing a memory impairing (2 h) or improving (6 h) effect of pharmacological treatments to be measured. Drugs were injected i.p. before the second trial (retrieval phase). This experimental procedure was first studied with scopolamine and DL-amphetamine, for which a significant deficit after a 2 h interval or improvement after a 6 h interval of performance was observed, respectively. The CCK(B) agonist, BC 264, was ineffective after a 2 h time interval, whereas the dose of 0.3 microg/kg significantly enhanced performance after a 6 h inter-trial interval. In contrast, BC 197 (30 microg/kg) produced a significant disruption of performance after a 2 h inter-trial interval but was without effect after a 6 h time interval. The effects of the two CCK(B) agonists were abolished by pretreatment with a selective CCK(B) antagonist, L365,260 but not by a selective CCK(A) antagonist, L364,718. The present results suggest that CCK(B) receptors display functional heterogeneity and that CCK(B) agonists like BC 264 could offer a new perspective for the treatment of attentional and/or memory deficits.

Amphetamine↗

PubMed1998

CCK in anxiety and cognitive processes.

Extensive studies were carried out on the involvement of the CCKergic system in anxiety-, panic- and stress-related behaviour. The stimulation of CCK-A or CCK-B receptors is implicated in the physical and psychological responses of CCK to stress. Furthermore, several selective CCK-B agonists produce anxiogenic-like effects, while CCK-B antagonists induce anxiolytic-like responses in several models of anxiety. However, BC264 a highly selective CCK-B agonist, does not produce anxiogenic-like effects but increases attention and/or memory. These effects are dependent on the dopaminergic systems. Together with biochemical data, this led to the hypothesis of the existence of two CCK-B binding sites, CCK-B1 and CCK-B2, which could correspond to different activation states of a single molecular entity. Investigations into CCK-B1 and CCK-B2 systems might be of critical interest, since only one site, CCK-B1, appears to be responsible for the effects of anxiety. Furthermore, the improvement of attention and/or memory processes by CCK, through CCK-B2 receptors, could offer a new perspective in the treatment of attention and/or memory disorders.

Animals↗

PubMed1997

Dual modulation of dopamine release from anterior nucleus accumbens through cholecystokinin-B receptor subsites.

Previous binding studies have suggested the existence of two affinity states for cholecystokinin-B (CCK-B) receptor. One study, using BC 197 and BC 264, two highly selective CCK-B agonists, has shown that BC 197 is selective for one subsite, B1, and that BC 264 has the same affinity for the two subsites, B1 and B2. Therefore, the possible involvement of CCK-B subsites in the modulation of endogenous dopamine (DA) release from slices of the anterior part of the nucleus accumbens was investigated with these two agonists in order to associate a functional response with activation of each subsite. The selective B1 agonist BC 197 produced a dose-dependent increase of 35 mM K(+)-stimulated DA release. In contrast, at a low concentration (20 nM), BC 264 inhibited the K(+)-evoked DA release, whereas at a higher concentration (1 microM), it stimulated the DA release. These two opposing effects were suppressed by the CCK-B antagonist PD-134,308, but not by the CCK-A antagonist L-364,718 and were not prevented by tetrodotoxin, a Na(+)-channel blocker. Moreover, BC 264 at 20 nM, in the presence of PD-134,308 at a concentration that would block the B2 subsites (0.1 nM), increased the evoked DA release. All together, these results support further the existence of distinct CCK-B subsites and suggest that, in the anterior nucleus accumbens, their stimulation mediates opposite effects on K(+)-stimulated DA release via a presynaptic mechanism.

Animals↗