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Guy Sandner

Publications and source records attributed to Guy Sandner.

11 recordsLinked to original sources

Adrenergic drugs modify the level of noradrenaline in the insular cortex and alter extinction of conditioned taste aversion in rats.

We compared the effect of conditioned taste aversion in rats by measuring the amount of sucrose that they drunk after conditioning, which differed according to whether rats had drunk the sucrose freely (SD: self drinking) during the conditioning session, or had been forced to drink it (IO: intra-oral administration through a chronically implanted cannula). The SD procedure delayed the extinction of conditioned taste aversion. Enhanced arousal, alertness, awareness or attention in the SD condition may have strengthened the memory of the taste. Brain noradrenergic networks are involved in such processes. We administered two noradrenergic drugs that produce opposite effects on noradrenaline release in the brain, methoxy-idazoxan, RX821002 (1mg/kg, i.p.), and guanfacine (0.12mg/kg, i.p.). We evaluated their effect (i) on the level of noradrenaline in the gustatory cortex using microdialysis, (ii) on glycaemia that is an essential factor of taste learning and (iii) on the comparative SD versus IO conditioned taste aversion protocol mentioned above. Injecting RX821001 increased the level of noradrenaline in the gustatory cortex up to two-fold of the baseline. This effect lasted 1h. The same dose of RX821002 did not elicit any alteration of glycaemia. It enhanced extinction of conditioned taste aversion in the SD group of rats. Injecting 0.12mg/kg of guanfacine produced the opposite effect. The noradrenaline level of the gustatory cortex decreased, but only down to 20% of the baseline. This decrease lasted 2h. Guanfacine increased glycaemia. Extinction of conditioned taste aversion was only marginally decreased by guanfacine in the SD group of rats. These results fit with Aston-Jones' point of view that the role of the noradrenergic coeruleo-cortical system may be to enhance arousal, alertness, awareness or attention to an event by a transient increase of cortical noradrenaline.

Adrenergic Agents↗

[Experimental models of schizophrenia--a review].

OBJECTIVE: Diagnostic and therapy of somatic diseases like diabetes and hypertension have improved notably with the use of experimental models. For schizophrenia the proposal of a model has made little impact and even scepticism. Nevertheless the most recent studies indicate that "Cognitive Sciences" applied to specific models may help us to find out mechanisms of the disease. This article reviews the models presently under investigation for schizophrenia. RESULTS AND DISCUSSION: The difficulty to model schizophrenia results from the subjectivity of its symptoms, the difficult to reproduce them in animals and the disease complexity. Research on such a complex phenotype can only proceed by separating its components (endophenotypes) from each other and by the respective manipulation of its experimental counterparts, made by specific interventions (e.g. pharmacological, surgical, genetic), in the search of a common mechanism leading to these endophenotypes. For integrating these findings with symptoms a global explanatory theory is required. So far, the disease seems to result from a diffuse neuronal disconnection as a consequence of minor brain abnormalities with a genetic and/or environmental cause. CONCLUSIONS: An integrative approach of the diversity of models presently used may improve our understanding of schizophrenia.

Animals↗

Aversive effects elicited by electrical stimulation of the inferior colliculus in normal and audiogenic seizure susceptible rats.

Trains of electrical stimulations were applied to the dorsal or ventral part of the inferior colliculus (IC) of audiogenic seizure susceptible rats from the AGSR strain. Threshold and duration of wild running (WR), were evaluated in the first experiment. All stimulation sites elicited WR, even in normal control rats. Stimulation of the IC of AGSR rats required a lower quantity of current, i.e., such brain sites were more sensitive to the current, than normal controls. The duration of post-stimulus WR was shorter in AGSR rats. Lower quantities of current applied to the ventral IC were needed to elicit WR than to the dorsal IC in AGSR rats. In a second experiment, using the same stimulations sites in the same rats, the emotional effect of the stimulation was tested through an instrumental learning procedure (switch-off paradigm) in which the rat was trained to press a bar to put an end to the stimulation. Both dorsal and ventral IC stimulation sites sustained switch-off behavior in AGSR rats, but only ventral IC stimulation sites sustained switch-off learning in control rats.

Acoustic Stimulation↗

Prenatal exposure of Long-Evans rats to 17alpha-ethinylestradiol modifies neither latent inhibition nor prepulse inhibition of the startle reflex but elicits minor deficits in exploratory behavior.

Prenatal administration of synthetic estrogens in humans as well as lower mammals was reported to alter behavior in adulthood. The alterations remain to be characterized according to specific pathophysiological hypotheses. In this study, three common behavioral models of schizophrenia were tested, i.e., latent inhibition (LI), prepulse inhibition of the startle response (PPI) and hyperlocomotion under amphetamine. Female Long-Evans rats were injected i.p. with a solution of 17alpha-ethinylestradiol (15 microg kg(-1)) everyday from day 9 to 14 of pregnancy, and behavioral characteristics of their offspring, raised by Wistar foster mothers, were compared to those of rats born from dams injected with the vehicle only, over the same gestation period. LI was tested in a conditioned taste aversion and a conditioned passive avoidance paradigm followed by a parametric study of PPI and an evaluation of locomotion in an open field under saline or amphetamine (1.5 mg kg(-1)). Histological brain measurements were also carried out in a subset of the same rats. Neither LI nor PPI was altered using methods that had proven sensitive in previous pharmacological studies. Treated rats' locomotion was impaired, but amphetamine did not elicit a differential enhancement. A thinner Amon's horn layer was observed in their hippocampus. This indicates that standard models of schizophrenia did not fit to the behavioral abnormalities found by others and confirmed in this study. They were not due to the abnormal maternal care to pups elicited by the treatment.

Amphetamine↗

Insular cortex lesions alter conditioned taste avoidance in rats differentially when using two methods of sucrose delivery.

The insular gustatory cortex may be essential for the evaluation of saliency and representation of the incentive values of tastes. Gustatory cortex lesions should interfere with conditioned taste avoidance according to these factors, which depend on the conditioned taste avoidance protocol used. The present study was aimed at investigating the effects of bilateral lesions of the gustatory cortex-focusing on electrolytic and excitotoxic lesions. Lesioned and sham-operated male Long-Evans rats were intoxicated using LiCl after drinking sucrose from a tube (SD) or having the same amount of sucrose fed directly into their mouths through a chronically implanted intra-oral (IO) cannula. Every aspect of the experiment was carefully counterbalanced between the experimental groups. In the control groups, the acquired avoidance towards sucrose was strongly preserved over eight extinction test days in SD rats but not in IO rats, in which a progressive decline was recorded. Electrolytic gustatory cortex lesions impaired but did not suppress conditioned taste avoidance in both protocols. Excitotoxic lesions tend to impair CTA also, but differentially according to the SD or IO protocols. Extinction of CTA was selectively impaired in the SD protocol by small lesions destroying the anterior insular cortex.

Animals↗

Frontal lesions do not alter the differential extinction of taste aversion conditioning in rats, when using two methods of sucrose delivery.

The frontal cortex is involved in the planning of behavioural responses and in the processing of their outcomes. Thus it contributes to several learning mechanisms, including those of conditioned taste aversion (CTA). A solution of sucrose drunk freely by a rat from a drinking tube-self-drinking protocol (SD)-was used as a conditioned stimulus in CTA. The intake of this solution was followed by gastric malaise. It produced an aversion to sucrose that withstood extinction over a week of repetitive tests. But, when the sucrose was perfused intra-orally (IO), i.e. not depending on any specific action by the rat, the extinction of aversion was much faster. Several factors may explain this differential extinction including the contribution of contextual factors linked to the achievement of an action and/or the enhancement of the attention towards the outcome of the action (the taste). The processing of such factors is usually believed to require the prefrontal cortex or the cingulate cortex (CgC). In our first experiment, the frontal cortex was totally transected. In the second experiment, the CgC was removed by aspiration. None of these lesions elicited any change in CTA, either in IO or in SD conditions, meaning that the differential extinction remained. The surprising absence of a frontal lesion effect was thought to indicate the low attentional demand required in both CTA protocols.

Animals↗

Enhancement of acoustic evoked potentials and impairment of startle reflex induced by reduction of GABAergic control of the neural substrates of aversion in the inferior colliculus.

The neural network of the inferior colliculus (IC), implicated in the generation of defensive behavior to aversive acoustic stimuli, is under tonic GABAergic control. Dopamine also seems to have a modulatory role in these neural circuits. It is still unclear how such changes in transmission of acoustic information influence the motor expression of the defensive behavior. Startle reaction to a sudden noise has been used as an effective way to measure the motor reactivity of rats to fearful acoustic stimuli. In this work we examined the processing of sensorial information--assessed by the recording of auditory evoked potentials (AEP)--and the behavioral effects--evaluated by the freezing and startle responses--during the reduction of GABA levels caused by microinjections of semicarbazide (SMC, 6 microg/0.2 microl), a glutamic acid decarboxylase inhibitor, into the IC. These data were compared to the effects of the overall arousal elicited by apomorphine (APO, 0.5 mg/kg, i.p.). The results obtained show that IC microinjections of SMC induced freezing behavior, enhanced the AEP and impaired the startle reaction to a loud sound. On the other hand, APO changed neither the AEP nor the startle in the same experimental conditions. These results suggest that the release of GABAergic control of the neural substrates of aversion in the IC results in an increased processing of auditory information along with an inhibitory influence on the motor pathways responsible for the startle response.

Acoustic Stimulation↗

Enhancement of latent inhibition by chronic mild stress in rats submitted to emotional response conditioning.

This work evaluated the influence of chronic mild stress on latent inhibition (LI) in rats, using a conditioned emotional response (CER) procedure. Rats were assigned to four groups: a non pre-exposed control group (NPC), a non pre-exposed stressed group (NPS), a pre-exposed control group (PC), and a pre-exposed stressed group (PS). Stressed animals were submitted to a chronic mild stress (CMS) regimen for three weeks. The off-baseline conditioned emotional response procedure had four phases: licking response training, tone-shock conditioning, retraining, and testing. Conditioning consisted of 2 tone (30 s) and shock (0.5 s) associations. Tone-shock conditioning evidenced by NPS and NPC groups suggests that stress did not interfere with the expression of a conditioned emotional response. Pre-exposure was carried out using 6 tones (30 s) during 2 sessions before conditioning. Prior exposure to the tone resulted in a decrease in learning that was greater in stressed animals. The results indicate an increase in latent inhibition induced by chronic mild stress. Such LI potentiation after CMS may be related to dopamine (DA) neurotransmission reduction in the central nervous system.

Acoustic Stimulation↗

Effects of ketamine and apomorphine on inferior colliculus and caudal pontine reticular nucleus evoked potentials during prepulse inhibition of the startle reflex in rats.

Prepulse inhibition (PPI) of the startle reaction to a strong sound is the reduction of this reaction elicited by a weak stimulus, a tone for example, when it precedes the startling sound. Its pharmacological sensitivity has been used to characterize antipsychotic drugs. Not much is known about the level of action of such drugs in the neuronal network involved in PPI. In the present study, evoked potentials from two key structures, the inferior colliculus (IC) and the caudal pontine reticular nucleus (PnC), were obtained in freely moving rats during standard startle and PPI tests, under ketamine (5 mg/kg) or apomorphine (0.5 mg/kg). In the IC, the potential evoked by the noise did not vary whether tested in basic or PPI conditions. Only minor changes were elicited by the drugs. In the PnC, the noise elicited an evoked potential that was reduced under PPI conditions. This alteration of the evoked potential was reversed by ketamine. The results obtained with apomorphine were not homogeneous either when considering the behavioral or the electrophysiological results.

Acoustic Stimulation↗

Conditioned taste aversion using four different means to deliver sucrose to rats.

A solution of sucrose either to be drunk from a drinking tube-self-drinking procedure (SD)-or perfused intraorally as a consequence of nose-pokes-self-administration procedure (SA)-or perfused as a consequence of licking an empty tube (LA)-was paired with an LiCl-induced malaise in rats. The effects were compared to those of a procedure consisting of intraoral administration (IO) of sucrose not contingent to any specific action of the rat. Similar levels of conditioned taste aversion (CTA) were obtained but extinction in the IO procedure was quicker than in the SA procedure, which was itself quicker than in the SD procedure. Extinctions in the IO and LA procedures resembled one another and were quicker than in the SD procedure. A step towards deciding between several explanatory hypotheses of these differences was made by conducting two more experiments. The third experiment was based on reinstatement, or not, of the conditioning procedure for the test after standard IO extinction. CTA was produced only when SD was used both at conditioning and test. A fourth experiment was based on latent inhibition where the procedure was changed, or not, between preexposure and conditioning. Latent inhibition was absent only when the rats had been preexposed to sucrose with the SA procedure and conditioned with the SD procedure.

Animals↗