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J C Bizot

Publications and source records attributed to J C Bizot.

15 recordsLinked to original sources

Hippocampal theta rhythm in anesthetized rats: role of AMPA glutamate receptors.

The present study describes the effects of intraseptal infusions of 1 nmol AMPA and 12 nmol NBQX on both frequency and amplitude of physostigmine-induced theta rhythm in urethane-anesthetized rats. Infusion of AMPA increased the theta frequency. This effect was blocked by a prior infusion of NBQX. Infusion of NBQX decreased the theta amplitude, and this effect was not altered by AMPA. These results suggest that the septal AMPA/glutamate receptors exert subtle modulatory influences on septohippocampal cells involved in theta rhythm generation.

Animals↗

Nicotine improves memory in an object recognition task in rats.

Nicotine was investigated for its mnemonic effect in a two trials object recognition task. In the first trial, two copies of the same object were presented. In the second trial (24 h after), one of the familiar object and a new object were presented. The time spent exploring the new object by control rats was not significantly different from the exploration time of the familiar object, indicating that they did not remember the familiar object. Rats injected with nicotine before the first trial, after the first trial or before the second trial spent more time in exploring the new object than the familiar one at the second trial. These results suggest that, in normal rats, acute nicotine enhances acquisition, consolidation and restitution of the information in an object recognition task.

Animals↗

Intraseptal infusions of a low dose of AP5, a NMDA receptor antagonist, improves memory in an object recognition task in rats.

The present study describes the effects of intraseptal microinjections of 2 nmol of AP5 upon memory of rats subjected to a two trial object recognition task. This task allows us to detect either a disruption or an improvement of memory according to the duration of the interval between the sample trial (T1) and the choice trial (T2). AP5 injected before T1 did not disrupt memory in a schedule able to detect an amnesia. In a schedule able to detect an improvement of memory, AP5 injected either 10 min before or just after T1, or 10 min before T2, improved retention. These results suggest that microinjection of a low dose of AP5 in the septum improves the acquisition, the consolidation and the restitution of the information in a working memory task.

2-Amino-5-phosphonovalerate↗

Effects of intraseptal infusions of N-methyl-D-aspartate receptor ligands on memory in an object recognition task in rats.

The present study describes the effects of intraseptal microinjections of N-methyl-D-aspartate (NMDA) or AP5, an agonist and an antagonist of the NMDA receptors, respectively, upon memory of rats. Animals were injected with the drug or vehicle immediately after the first exposure to two identical objects, and the duration of exploration of the familiar and a new object were evaluated 45 min or 24 h later. Vehicle-treated rats explored the new object longer than the familiar object when the intertrial time was 45 min, indicating that they remembered the familiar object, but not when the intertrial time was 24 h. The difference of exploration time between the objects was increased by NMDA, but not by AP5, when the intertrial time was 24 h, and decreased by AP5 when the intertrial interval was 45 min. These results suggest that NMDA and AP5 improves and disrupts, respectively, the consolidation in a working memory task.

2-Amino-5-phosphonovalerate↗

Pharmacological profile of CEB-1957 and atropine toward brain muscarinic receptors and comparative study of their efficacy against sarin poisoning.

This study consists of two parts, first to compare the pharmacological profile of atropine and CEB-1957 substance toward muscarinic receptor subtypes. In various rat brain structures, binding properties were determined by competition experiments of [3H]pirenzepine, [3H]AF-DX 384, and [3H]4-DAMP in quantitative autoradiography of M1, M2, and M3 muscarinic receptor subtypes, respectively. Competition curves have shown that atropine presents similar nanomolar inhibition constants toward each subtype, while CEB-1957 has distinct affinities (Ki from 0.26 to 73 nM) with the following range order: M3 > or = M2 > M1. The second part is to compare atropine and CEB-1957 (in combination with pralidoxime) for their ability to protect against the lethality induced by 2 x LD50 of the acetylcholinesterase inhibitor sarin. CEB-1957 reduced the mortality at doses 10 times lower than atropine. Finally, from these results, it is proposed that a selective blockade of M2 and M3 receptor subtypes could play a pivotal role in the protective effect against sarin poisoning.

Animals↗

Brain neurotoxicity of Penitrem A: electrophysiological, behavioral and histopathological study.

The neurotoxicity of Penitrem A (PA) in rats was assessed against neurophysiological, behavioral and histopathological parameters. Animals were acutely given intracerebroventricular (22-45 mg) or intraperitoneal injections (0.5-1.5 mg/kg) of PA. A typical trembling syndrome associated with PA was always noted. Depending on the dose administered, animals may convulse and eventually die (1-1.5 mg/kg). PA-induced transient alterations of the EEG involving an increase in the frequency and voltage of electrical activity recorded from the cerebral cortex. Hippocampal activity was not modified and some pathologic activities may be recorded at the thalamus. Generally these EEG alterations disappeared at d 3 after the injection and the animals progressively recovered. However in the most severe cases, neuromotor disturbances were maintained at d 7 (rotarod test). Coronal sections of the brain at the striatal, thalamic, hippocampal and pons levels mainly revealed that PA was able to induce dose related injuries in the cerebellum with massive degeneration of Purkinje cells and a significant vacuolization within the molecular layer. The neurotoxic mechanism remains unclear. Action of the mycotoxin on the cerebello-thalamo-cortical tract is discussed.

Animals↗

Effects of various drugs including organophosphorus compounds (OPC) and therapeutic compounds against OPC on DRL responding.

The effects of various drugs were assessed in rats responding under a Differential-Reinforcement-of-Low-Rate 30-s (DRL 30-s) schedule. Atropine, scopolamine, and CEB-1957 (a new muscarinic blocker) increased response rate and decreased reinforcement rate, while methylatropine only decreased reinforcement rate. Physostigmine decreased response and reinforcement rates, when pyridostigmine had few effect on DRL responding. The irreversible acetylcholinesterase (AChE) inhibitors organophosphorus compounds (OPC) soman and sarin, injected at one-third of the LD50 did not consistently alter DRL performance, suggesting that they produce few behavioral effects in the rat when administered at subtoxic doses. Three oximes--pralidoxime, pyrimidoxime, and HI-6--decreased both response and reinforcement rates. Mecamylamine had few consistent effects on performance, and nicotine, d-amphetamine, diazepam, and the wakening drug modafinil increased response rate and decreased reinforcement rate. These two latter drugs also increased the number of very premature responses. These results, taken together, indicate that a DRL schedule is a useful tool to bring to light the existence of psychotropic effects of a drug. The explanation of drug-induced alterations of DRL performance, in terms of effects on cognition or on mood, is also discussed.

Animals↗

Effect of apamin, a selective blocker of Ca2+-activated K+-channel, on habituation and passive avoidance responses in rats.

The effects of apamin, a selective blocker of the small conductance K(Ca) channels were examined in both passive avoidance and habituation of exploratory activity in rats. In the two experiments, animals were subjected to two trials separated by a 24 h interval. Apamin was administered either before or after the first session (acquisition) or before the second session (restitution). In the passive avoidance test, apamin did not alter performance whenever the time of administration. In the habituation task, apamin (0.4 mg/kg) decreased activity (distance travelled, rearing) on the two sessions only when it was injected before acquisition but not when injection took place just after the acquisition session or before the restitution session. Taken together, these findings support the view that the blockade of apamin sensitive K(Ca) channels improved the acquisition in non-stressful task, but not in a stressful situation.

Analysis of Variance↗

Apamin improves learning in an object recognition task in rats.

Object recognition was investigated in rats in a two trial unrewarded task. In the first trial, two copies of the same object were presented. In the second trial, one of the familiar object and a new object were presented. Rats explored the new object longer than the familiar object when the intertrial time was 1 h, indicating that they remembered the familiar object, but not when the intertrial time was 24 h. Rats injected with apamin (a toxin which blocks specifically Ca(2+)-activated K(+)-channels) before the first trial spent more time in exploring the new object than the familiar object at the second trial, when it took place 24 h after the first trial. Injection of apamin just after the first trial or before the second trial did not modify the difference in exploration time between the new and the familiar object. These results suggest that the blockade of Ca(2+)-activated K(+)-channels could improve learning, but not consolidation nor restitution of the information, in an object recognition task.

Analysis of Variance↗

Effects of penitrem A on rat's performances in passive avoidance and Morris water maze tests.

Intraperitoneal administration of the mycotoxin penitrem A 30 min before a training session in passive avoidance task, impaired performance of rats subjected to a test-session 24 h after. This effect was not antagonised by pretraining administration of physostigmine or bicuculline. Administration of penitrem A 20 min before a training session or 30 min before a test-session did not impair performance. In the Morris water maze, doses of penitrem A that induces slight to moderate tremors, but not a lower dose, disrupted place learning. These results suggest that penitrem A disrupts the processes that take place at the time of acquisition, but not those just after acquisition, and does not alter the restitution of information. This effect would not be related to a decrease of cholinergic neurotransmission nor to a stimulation of GABA A receptors. Nevertheless, it could not be totally excluded that the performance impairments induced by penitrem A would be secondary to a motor disruption.

Animals↗

Effects of psychoactive drugs on temporal discrimination in rats.

Male Wistar rats were trained, in two-lever operant chambers, to press one lever (L5) after the presentation of a conditioned stimulus (a light) for 5 s (CS5) or the other lever (L20) after a conditioned stimulus for 20 s (CS20). Various drugs were administered before experimental sessions, during which CS5, CS20 and a stimulus of the intermediate duration of 12 s (CS12) were randomly presented. Rats pretreated with vehicle made approximately 50% of presses on L5 after the presentation of CS12. Atropine, diazepam, desipramine, clomipramine and moderate doses of haloperidol or of scopolamine increased the percentage of responses made on L5 after the presentation of CS20 and/or CS12. These effects could be due to a reduction of the speed of an internal clock. High doses of either haloperidol or scopolamine decreased the percentage of correct responses, an effect that was interpreted as a disruption of temporal discrimination. Nicotine and d-amphetamine decreased the percentage of responses made on L5 after the presentation of CS5 and/or CS12, an effect that could reflect an acceleration in the speed of the internal clock. Physostigmine, buspirone, mianserin and piracetam did not consistently alter performance, suggesting that these drugs do not affect timing processes.

Animals↗

Impulsivity as a confounding factor in certain animal tests of cognitive function.

Performance in cognitive tasks which require the subject to wait and/or to process a large amount of information can be disrupted by an increase in impulsive-like behaviour. Accordingly, a decrease in impulsive-like behaviour can improve performance in such tasks. Conversely, impulsive-like behaviour may improve performance in cognitive tasks where simple and fast responses and/or only little information processing is required. Thus, impulsivity constitutes a confounding factor in studies of cognitive function. Impulsive-like behaviour may be modified by serotonergic (5-HT) activity, with underactivity in 5-HT neurotransmission increasing impulsivity and vice versa. Drug- or lesion-induced alteration in 5-HT neurotransmission may, therefore, constitute suitable tools to investigate the role of impulsivity in animal tests of cognitive function. Benzodiazepines also increase impulsive-like behaviour, possibly by decreasing 5-HT neurotransmission. Hence, the effects of modulation of 5-HT systems and of the benzodiazepine-binding site on performance in animals tests of cognitive function will be discussed. It is predicted that the effects of manipulations of serotonergic activity or of benzodiazepine administration depend upon the nature of the response required, and that these effects may be mediated through changes in impulse control.

Animals↗

Opposite effects of cholinergic agents and benzodiazepine receptor ligands in a passive avoidance task in rats.

Benzodiazepine (Bzd) agonist, diazepam (Dzp) and inverse agonist methyl beta-carboline-3-carboxylate (beta-CCM); acetylcholinesterase inhibitor, physostigmine (Physo) and muscarinic antagonist, scopolamine (Scopo), were investigated for their mnesic effect in a passive avoidance (PA) task in rats. Impairments were observed after Dzp- and/or Scopo-pretraining treatments. Physo was without effect but antagonized the Dzp-induced impairments. beta-CCM enhanced acquisition and antagonized the Scopo-induced impairing effect. All these drugs had no effect in posttraining administration.

Animals↗

Effects of imipramine-like drugs and serotonin uptake blockers on delay of reward in rats. Possible implication in the behavioral mechanism of action of antidepressants.

This study investigated in rats the action of a variety of antidepressants in two behavioral models. In model 1, animals trained in a T-maze were allowed to choose between 2 magnitudes of reward: immediate but small reward (2 pellets) vs. a 25-sec delayed but large reward (10 pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reward in less than 40% of the trials. Desipramine 8 mg/kg, clomipramine 8 mg/kg, maprotiline 8 mg/kg, indalpine 2 to 4 mg/kg, zimelidine 8 to 16 mg/kg, nialamide 16 to 32 mg/kg and clenbuterol 0.03 to 0.06 mg/kg significantly increased the number of choices of the large-but-delayed reward. In model 2, rats were subjected to a fixed ratio 48 schedule of food reinforcement; after completion of a series of exactly 48 presses a food pellet was delivered, and if no further press occurred, a sequence of free pellets was initiated according to fixed, increasing intervals (from 5-80 sec). Pressing during the sequence stopped it and required the rat to complete again the fixed ratio 48 to be reinforced and to reintiate the sequence. Waiting for free reward was significantly lengthened by desipramine 8, clomipramine 16, indalpine 8, zimelidine 8 to 16, nialamide 32 and clenbuterol 0.007 to 0.06 mg/kg. These results suggest that, possibly through noradrenergic and serotonergic mechanisms, antidepressants markedly enhanced rats' ability to wait for food reward, an affect which might reflect the ability of these drugs to improve impulse control. The relevance of such a property in the therapeutic action of antidepressants remains to be delineated.

Animals↗

Acute exposure to a low or mild dose of soman: biochemical, behavioral and histopathological effects.

Effects of low to mild doses of soman on central and blood cholinesterase (ChE) activities and anxiety behavior were studied in mice 30 min, 24 h and 7 days after poisoning. At these two latter time points, histopathological consequences of soman intoxication were also studied. The 30-microg/kg dose of soman produced 30 min after intoxication, about 35% of central ChE inhibition, and an anxiolytic effect without toxic signs or histopathological changes. The 50-microg/kg dose of soman produced at the same time, about 56% of central ChE inhibition, slight clinical signs of poisoning without convulsions, an anxiogenic effect with a slight hypolocomotion but no brain damage. A mild dose of soman (90 microg/kg) produced at this same time point about 80% of central ChE inhibition, and led to ataxia and tremors in every mouse and to convulsions in some of them. Thirty minutes and 24 h after poisoning, the behavioral tests revealed neither anxiolytic nor anxiogenic responses despite a clear hypolocomotion. Only mice that experienced long-lasting convulsions developed neuropathological changes. The functional implication of our results, as well as the biological relevance of blood vs. brain ChE levels, as an index of intoxication severity are discussed.

Amygdala↗