Biomedical subjects

G Di Scala

Publications and source records attributed to G Di Scala.

At least 37 records · Page 2Linked to original sources

PubMed1996

Effect of propofol on affective state as assessed by place conditioning paradigm in rats.

BACKGROUND: Whether propofol produces a pleasant affective state remains unclear from clinical studies. In the current study, the effect on affective state of subanesthetic and anesthetic doses of propofol was assessed at a preclinical level with rats in a place conditioning paradigm. Propofol was compared with methohexital. METHODS: In the place conditioning paradigm, propofol-induced effect was repeatedly paired with one of two distinguishable compartments of the apparatus, whereas the vehicle-induced effect was repeatedly paired with the other compartment. During a subsequent free-choice test, a preference for the drug-paired compartment over the vehicle-paired compartment would be indicative of pleasant state induced by the drug. For all experiments, the conditioning session lasted 8 days and consisted of four pairings of the drug with one compartment and four pairings of the equivalent volume of vehicle with the other compartment. In experiment 1A, four groups of rats were designated according to the dose of propofol that they received intraperitoneally: 0,30,60, or 90 mg/kg. In experiment 1B, the same procedure was used with subanesthetic doses of intraperitoneal methohexital: 0,10,20, or 30 mg/kg. In experiment 2, the rats were conditioned during the recovery period from short-term anesthesia. For one group, anesthesia was induced by propofol (100 mg/kg) whereas for the other group, anesthesia was induced by an equivalent anesthetic dose of methohexital (40 mg/kg). RESULTS: In experiment 1A, the 30-mg/kg, 60-mg/kg, and 90-mg/kg groups showed a place preference for the drug-paired compartment, but only the group conditioned with 60 mg/kg propofol significantly differed from the 0-mg/kg group. In experiment 1B, the groups conditioned with methohexital showed no place preference for the drug-paired compartment. In experiment 2, the rats showed a place preference for the compartment in which they recovered from propofol-induced anesthesia but no place preference for the compartment in which they recovered from methohexital-induced anesthesia. CONCLUSIONS: Propofol, but not methohexital, induced a pleasant affective state in rats at subanesthetic doses as well as during recovery from an anesthetic dose.

Affect↗

PubMed1996

[New antipsychotic agents: new paths of research on the notion of atypical agents].

The synthesis of new compounds called atypical neuroleptics such as amisulpride, clozapine, risperidone and now olanzapine has roused interest in the psychopharmacology of atypical antipsychotics. Since the synthesis of chlorpromazine in the early 1950s, subsequent therapeutic research has had two main goals: to define the mechanism of action of atypical neuroleptics and to search new compounds with both clinical efficacy and fewer side effects. The first one has widely been achieved, as it is clear that classical neuroleptics exert their effects by blockade of dopamine D2 receptors located in the ventral striatum. As a matter of fact, non specific blockade of dopaminergic receptors in the dorsal striatum also predicts extrapyramidal side effects. Moreover, classical neuroleptics have poor effects on negative and cognitive symptoms. That is why the search for new compounds has focused on two main goals: first, understanding the interactions of the neurotransmitters involved by the new drugs, second, characterizing their brain site of action. Achieving these two goals might enable us to precise the notion of atypicity as well as the classification of these new drugs.

Antipsychotic Agents↗

PubMed1995

Effects of GABAB receptor antagonists on two models of focal epileptogenesis.

The acute effects of two GABAB receptor antagonists (phaclofen and CGP-35348) were studied in two types of epileptogenic activity: that produced by intracortical injections of baclofen and that appearing after withdrawal of chronic intracerebral GABA infusion (the GABA-withdrawal syndrome, GWS). Intracortical baclofen induced two types of electrographic paroxysmal discharges: one consisting of single spike-and-wave (pattern I) and another of polyspike-and-wave patterns (pattern II). Both patterns showed similar latencies and temporal evolution of spike frequency discharges. Phaclofen, applied directly into the baclofen-induced epileptogenic focus, suppressed pattern II but was ineffective in modifying both pattern I and the GWS. CGP-35348, administered systemically, inhibited both patterns I and II. Intracortical microinjection of baclofen or phaclofen in rats showing a GWS had no effect, nor the systematically given CGP 35348. These results indicate a differential participation of GABAB receptors in GABA-related epileptic syndromes of cortical origin.

Animals↗

PubMed1995

c-fos immunoreactivity in the brain following electrical or chemical stimulation of the medial hypothalamus of freely moving rats.

c-fos immunoreactivity was used to map brain areas in which neurons reacted either to electrical stimulation or to microinjection of the excitatory amino acid kainate and of the GABAA antagonist, SR-95531, applied to the medial hypothalamus of freely moving rats. All these stimulations induced flight behavior of moderate intensity. Immunoreactive cells were found within a radius of 0.5 mm around the stimulated area. Distally, clusters of labeled cells were found ipsilaterally in the piriform and entorhinal cortices, in several amygdaloid nuclei, in the bed nucleus of the stria terminalis, in the septo-hypothalamic nucleus, in the paraventricular, anterior and dorsomedial hypothalamic nuclei, the the paraventricular thalamic nucleus, in the dorsal periaqueductal gray extending to the cuneiform nucleus, and bilaterally in the supramammillary decussation and the locus coeruleus. The specificity of the brain areas thus labeled was indicated by the unilateral pattern of activation as well as by the different pattern obtained after control microinjection of saline. Therefore, these results are likely to provide sound information about the brain structures involved in defensive-aversive behavior evoked from the medial hypothalamus.

Animals↗

PubMed1995

Neuroanatomical and functional specificity of the basolateral amygdaloid nucleus in taste-potentiated odor aversion.

The present study aimed at documenting the neurobiological substrate of taste-potentiated odor aversion (TPOA) in the rat. The role of several temporal lobe structures in discriminative TPOA learning was questioned. The effects of excitotoxic lesions (ibotenate) of the basolateral amygdaloid nucleus, the central amygdaloid nucleus, the caudate putamen nucleus, and aspirative lesion of the entorhinal cortex were studied. The results show that only basolateral amygdaloid nucleus (ABL) damage impaired TPOA. This effect was selective of TPOA, since it spared conditioned taste aversion (CTA) and olfactory perception. In order to find out which process in TPOA requires normal functioning of the ABL, the effects of microinjections of a GABAA agonist (muscimol) into the ABL at various stages of the experiment were examined. The results show that application of muscimol during the acquisition, before or after the presentation of the odor-taste stimulus, impaired TPOA without affecting CTA. Contrastingly, application of muscimol before the test impaired neither TPOA nor CTA. These results suggest that ABL is involved in the acquisition but not in the retrieval of TPOA. The efficacy of muscimol microinjected after the presentation of the odor-taste stimulus further suggests that the deficit is not due to a sensory impairment but rather to the disruption of a memory process, critical for TPOA.

Amygdala↗

PubMed1994

Chronic mianserin or eltoprazine treatment in rats: effects on the elevated plus-maze test and on limbic 5-HT2C receptor levels.

Rats were chronically treated with mianserin (10 mg/kg i.p.) or eltoprazine (1 mg/kg i.p.) and were tested in the elevated plus-maze test for anxiety. 5-HT2C (previously 5-HT1C, see Humphrey et al., 1993, Trends Pharmacol. Sci. 14, 223) binding sites and their mRNA were evaluated in limbic structures (i.e., amygdala, hippocampus, septum) of a sample of these rats by autoradiographic binding studies and in situ hybridization histochemistry. Mianserin and eltoprazine displayed opposite effects in the elevated plus-maze: mianserin induced anxiolytic-like effects, while eltoprazine showed anxiogenic-like ones. Within the amygdala, but not in other structures, the quantitative autoradiographic analysis of the 5-HT2C binding sites showed a differential effect: mianserin treatment induced a decrease in the number of these sites, while eltoprazine treatment resulted in an increase. In spite of this, neither mianserin- nor eltoprazine-treated rats displayed an alteration in the 5-HT2C receptor mRNA levels in the brain regions examined. Our results are suggestive of a relation between anxiolytic/anxiogenic-like effects and the level of 5-HT2C binding sites in the amygdala.

Acetylcholinesterase↗

PubMed1994

Distribution of lithium in the rat brain after a single administration known to elicit aversive effects.

In order to get insight into the brain areas involved in the initial unpleasant effects resulting from the administration of lithium (Li+), its distribution was mapped in the rat brain using the 6Li(n,alpha)3H nuclear reaction after a single injection of 6Li2SO4 at doses and latencies corresponding to the elicitation of such unpleasant effects. An improved method for visualization and measurement of local Li+ concentrations was used consisting in diffracting light along the tracks left by alpha particles in a dielectric detector. The distribution of Li+ was found less homogeneous than when Li+ was administered chronically. Periaqueductal and periventricular structures were the brain areas containing the highest concentrations of Li+.

Animals↗

PubMed1993

What brain structures are active during emotions? Effects of brain stimulation elicited aversion on c-fos immunoreactivity and behavior.

Aversive behavior is produced by stimulating some brain structures, such as the dorsal periaqueductal gray and the medial hypothalamus. We have used c-fos immunoreactivity to map brain areas which are influenced by stimulation of these two structures. Stimulation was produced in freely moving rats by electrical stimulation or by microinjections of either excitatory amino acids or GABA blocking drugs. Behavior was monitored to detect emotional changes. The effects on labeling induced by the stimulation of either structure were then compared. Structures labeled include the amygdala, the stria terminalis, the supramamillary area, the hypothalamus, the periaqueductal gray, the superior colliculus, the nucleus cuneiformis, and the locus coeruleus. Regardless whether chemical or electrical stimulation was used or the structure stimulated, there was a large overlap among the brain areas labeled. We then compared our results with data from the literature where other methods of inducing aversion have been used, including pain and stress. There was remarkable similarity in the patterning of labeling irrespective of the type of stimulation (central-peripheral, chemical-electrical). There was, however, one interesting difference produced by central vs. peripheral stimulation. Labeling was unilateral in the former case and bilateral in the latter case. Our results suggest that there is a neural substrate that mediates aversive behavior, no matter how it is produced. Nevertheless, that peripheral stimulation produces mainly bilateral activation of this substrate whereas central stimulation produces mainly unilateral activation suggests that natural peripheral stimuli are also integrated at a higher functional level. Future work could be directed toward explicit comparisons of central versus peripheral stimulation to identify the structures involved in higher level integration of aversive behavior.

Animals↗

PubMed1993

Evidence for state-dependent retrieval in conditioned place aversion.

State-dependent retrieval (SDR) in conditioned place aversion (CPA) was observed using Long-Evans male rats, with three different aversive drugs injected ip: lithium chloride (31.8 mg/kg), FG 7142 (10 mg/kg), and naloxone (5 mg/kg). Experiment 1 showed that state-dependent dissociation was complete with lithium chloride following two conditioning trials, but disappeared when the number of learning sessions was increased. Experiment 2 showed that following two conditioning trials, such complete state-dependent dissociations were also observed when FG 7142 or naloxone were used during conditioning. The results of this study showed that the expression of SDR is not monotonic in CPA paradigm but depends on the stage of learning. In addition, SDR can be observed following administration of a variety of drugs known to produce CPA, but differing in their neurochemical targets and the nature of the aversive effects they induce. Finally, these results are discussed with regard to what is known about SDR in other paradigms.

Animals↗

PubMed1993

Effect of 5,7-dihydroxytryptamine lesion on mianserin-induced conditioned place aversion and on 5-hydroxytryptamine1C receptors in the rat brain.

The lesion of serotonergic neurons (by an intraventricular injection of 5,7-dihydroxytryptamine) potentiated the conditioned place aversion induced by the 5-hydroxytryptamine1C/5-hydroxytryptamine2 antagonist mianserin in rats. This effect was selective for mianserin as the same lesion suppressed the conditioned place aversion induced by the benzodiazepine inverse agonist FG-7142. Previous results had shown the involvement of the 5-hydroxytryptamine1C receptors in the conditioned place aversion induced by mianserin [Rocha et al. (1993) Behav. Pharmac. 4, 101-106]. It was thus of interest to investigate the effect of the lesion on these receptor binding sites. Autoradiographic binding studies showed that the lesion significantly increased the concentration of the 5-hydroxytryptamine1C binding sites in various brain regions, including the amygdala, the hippocampus and the nucleus accumbens. Contrastingly, in these same brain regions, in situ hybridization histochemistry did not reveal an alteration of the level of messenger RNA coding for these receptors. On the one hand, correlating potentiation of the aversive effects of mianserin and increase of 5-hydroxytryptamine1C binding sites in the limbic system represent an interesting step in the comprehension of the molecular and motivational effects of serotonergic drugs. On the other hand, showing a dissociation between the expression of 5-hydroxytryptamine1C receptors and their corresponding messenger RNA, suggest that post-transcriptional mechanisms are involved in the regulation of these receptors.

5,7-Dihydroxytryptamine↗

PubMed1992

C-fos immunoreactivity in the brain following unilateral electrical stimulation of the dorsal periaqueductal gray in freely moving rats.

C-fos immunoreactivity was used to reveal brain areas in which neurons were influenced by electrical stimulations applied to the dorsal periaqueductal gray. These stimulations were applied in freely moving rats so that the resulting behaviors could be observed. Shortly afterwards, the brains of the rats were processed for C-fos immunoreactivity. In order to determine the specificity of the brain areas thus labeled, control stimulations were applied to the ventral tegmental area of other rats. Immunoreactive cells were found surrounding the tip of the stimulation electrode within a radius of 0.5 mm. This labeled area extended further along the rostro-caudal axis than along the medio-lateral or dorso-ventral axis in the periaqueductal gray. Distally, clusters of labeled cells were found ipsilaterally in the caudal periaqueductal gray extending to the nucleus cuneiformis, and bilaterally in the locus coeruleus and supramamillary decussation. More widespread labeling was found in most hypothalamic subareas and in the lateral habenula. The labeled brain areas following ventral tegmental area stimulations were totally distinct, and comprised the medial forebrain bundle, the nucleus accumbens, the vertical limb of the diagonal band and the medial septum. The pattern of labeling produced by periaqueductal gray stimulations was therefore specific, and provided information about brain structures involved in the motivational and behavioral effects of such stimulations.

Animals↗

PubMed1992

Wild running elicited by microinjections of bicuculline or morphine into the inferior colliculus of rats: lack of effect of periaqueductal gray lesions.

Bicuculline methiodide, a GABAA receptor antagonist, or a high dose of morphine was injected at the same site within the inferior colliculus (IC) of rats. Both drugs elicited the same behavioral activity (wild running). However, the time course and magnitude of the effects of the two drugs differed. Since the behavioral activation elicited was reminiscent of what was found with microinjections of bicuculline methiodide or morphine into the periaqueductal gray (PAG), we lesioned the PAG in another group of rats. It was found that extensive lesions of the PAG including those extending to the medial part of the superior colliculus did not significantly reduce the wild running.

Animals↗

PubMed1992

Conditioned place preference induced by Ro 16-6028, a benzodiazepine receptor partial agonist.

A place conditioning situation was used to assess the putative affective properties of benzodiazepine receptor ligands in the rat. The benzodiazepine receptor partial agonist Ro 16-6028 induced a conditioned place preference, suggesting that this compound has rewarding properties. The benzodiazepine receptor antagonist Ro 15-1788 induced neither place preference nor aversion, but prevented the place preference induced by Ro 16-6028, suggesting that the rewarding effects of Ro 16-6028 are due to its action on the benzodiazepine receptor. The benzodiazepine receptor full agonist diazepam did not induce a conditioned place preference in our hands, in contrast with previous studies. The sensitivity of place conditioning with benzodiazepine ligands to situational factors, such as the existence of a preconditioning preference, is discussed.

Animals↗

PubMed1991

Behavioural, pharmacological and biochemical effects of acute and chronic administration of ketamine in the rat.

The effects of N-methyl-D-aspartate (NMDA) antagonist ketamine given acutely or chronically were investigated on dopamine-related motor functions. Acute administration (15, 22.5, 30 mg/kg, i.p.) reversed the catalepsy induced by a dopamine (DA) antagonist (haloperidol, 0.25 mg/kg, i.p.) in the rat. When given orally and chronically (15 mg/kg per day) during at least 60 days, no alteration of spontaneous motor behaviour was observed, but the responsiveness to a DA agonist (apomorphine, 0.125 or 0.25 mg/kg s.c.) and to haloperidol was enhanced, suggesting an hypersensitivity of the DA receptors following the chronic blockade of NMDA receptors. However, following prolonged administration of ketamine there were no alteration of DA levels and turnover. Taken together these results suggest that the mechanisms involved in this DA receptor hypersensitivity should be postsynaptic.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Periaqueductal gray spike trains recorded in frontal or horizontal mesencephalic brain slices from the rat.

Spontaneous spike trains were recorded from the periaqueductal gray matter (PAG) in frontal and horizontal mesencephalic slices in order to compare spontaneous activity of the slice preparation to previous in vivo records. The firing rates resembled those recorded in vivo. They were low notwithstanding the fact that the slicing procedure removed tonic inhibitory input to the PAG. The firing rates increased caudo-rostrally, a fact that had not been reported in vivo, and were lower in frontal sections. Several different spike trains were found, described and classified according to their temporal firing patterns. The spike sequences were usually simple stochastic processes, distributed as a Gaussian function with or without stochastic deletion of spikes.

Animals↗

PubMed1991

Discriminative properties of aversive electrical stimulations of the so-called "mesencephalic locomotor region": a parametric study.

The classical 2-lever food-reward-reinforced discrimination paradigm, although already successfully applied to study discriminative properties of positively reinforcing electrical brain stimulations (EBS), has not yet been used for negatively reinforcing (aversive) EBS. This study was aimed at assessing if such a discrimination paradigm could be used to demonstrate discriminative properties of aversive EBS of the so-called "mesencephalic locomotor region" (MLR). Fourteen rats were trained for food reward to press one lever in the presence of EBS of the MLR and the other lever in the absence of EBS. Discriminative control by EBS of the MLR was obtained in 11 rats, which were subsequently subjected to a parametric study. It was found that the discriminative properties of EBS of the MLR covaried with changes in the intensity, frequency and pulse duration of the EBS. Our data also suggest that the aversive dimension of the stimulation might constitute a component of the discriminative cue induced by these EBS.

Animals↗

PubMed1991

Wild running and switch-off behavior elicited by electrical stimulation of the inferior colliculus: effect of anticonvulsant drugs.

The behavioral and motivational effects of electrical stimulation of the inferior colliculus (IC) were investigated. Electrical stimulations of either the dorsal part or ventral part of the IC both elicited wild running (WR). Nevertheless, the ventral part was found more sensitive than the dorsal part, as lower intensities were needed to elicit WR. Moreover, WR differed depending on the part of the IC stimulated. It stopped as soon as the stimulation was switched off when the ventral IC was stimulated, whereas it further persisted in a poststimulus WR when the dorsal IC was stimulated. This poststimulus WR was abolished by anticonvulsant drugs such as diazepam, phenytoin or sodium valproate. In an operant escape conditioning paradigm (switch-off test), only stimulation of the ventral IC readily sustained switch-off learning. Dorsal IC stimulations did not, possibly because of the poststimulus enduring effects of the stimulation, as evidenced by poststimulus WR. Indeed, the anticonvulsant drugs which abolished this poststimulus WR also permitted switch-off of dorsal IC stimulations. It is concluded that electrical stimulations of the IC (dorsal or ventral) elicit aversive effects and that WR elicited either by ventral or dorsal stimulation may represent the overt expression of these aversive effects.

Animals↗

PubMed1990

Chronic infusions of GABA into the medial frontal cortex of the rat induce a reversible delayed spatial alternation deficit.

The effects of bilateral infusions of GABA into the medial frontal cortex of the rat were studied in a delayed spatial alternation task. It was found that GABA (500 mM, 1 microliter/h during 7 days) impaired the performance of the rats in the previously learned task. Upon interruption of the treatment, the animals rapidly recovered normal performance scores. The results show that GABA infusions produce functional deficits similar to those produced by lesions of the frontal cortex. Moreover, the deficits are reversible upon interruption of the treatment. This technique may therefore be a useful tool for studying frontal lobe functions and the involvement of GABAergic mechanisms in cognitive processes.

Animals↗