Biomedical subjects

G Sandner

Publications and source records attributed to G Sandner.

At least 37 records · Page 2Linked to original sources

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

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

Behavioral analysis of the effects of benzodiazepine receptor ligands in the conditioned burying paradigm.

In the conditioned burying paradigm, 10 mutually exclusive behavioral sequences were encoded in order to characterize the effects of various benzodiazepine receptor ligands. It was found that each ligand produced a specific behavioral pattern, the elements of which were consistent with results obtained in other experimental situations. Whereas anxiolytic (diazepam, Ro 16-6028) and 'anxiogenic' ligands (FG 7142) both decreased the mean duration of burying, these two classes of drugs largely differed when approaches to the prod and escape movements away from the prod were considered. The benzodiazepine receptor antagonist Ro 15-1788 was devoid of effects on all of the behavioral sequences considered. The main characteristics of these behavioral profiles persisted during an extinction test, although the animals were no longer treated. It is proposed that additional behavioral measures, or better, an ethological analysis of the behavior may increase the potency of the conditioned defensive burying paradigm.

Animals↗

PubMed1990

Aversion induced by electrical stimulation of the mesencephalic locomotor region in the intact and freely moving rat.

Electrical stimulation of the so-called "mesencephalic locomotor region" (MLR) in the acute mesencephalic and restrained rat is known to induce locomotion. In the intact and freely moving rat, electrical stimulation of an area coextensive with MLR is reported to elicit an apparently aversive type of behavioral response. Indeed, the description of this behavioral response is very similar to the description of the prototypical escape reaction elicited by electrical stimulation of the periaqueductal gray (PAG), a structure of the so-called "brain aversive system." In this study, we investigated if, as is the case for PAG stimulations, these MLR electrical stimulations are also aversive in nature. To that end, MLR-stimulated rats were subjected to the switch-off test, in which the stimulated rat learns to interrupt the stimulation by pressing a bar. It was found that electrical stimulation of MLR sites, positive for apparently aversive behavior, supports the learning of the switch-off behavior, which demonstrates the aversive nature of such stimulations. Furthermore, the switch-off latency (time elapsed between the onset of the stimulation and its offset by a press of the bar) was shown to decrease when the intensity of the electrical stimulation is increased or when the interpulse interval is decreased, which suggests that the generated aversive state is graded by the strength of the stimulation. It is, hence, proposed to extend the "brain aversive system" to the MLR.

Animals↗

PubMed1990

Differential pharmacological reactivity of aversion induced by stimulation of periaqueductal gray or mesencephalic locomotor region.

Rats were trained to switch-off aversive electrical brain stimulations applied to the periaqueductal gray (PAG) or mesencephalic locomotor region (MLR) by pressing a bar (switch-off behavior). We investigated the effects of IP injections of the benzodiazepine (BZ) receptor inverse agonist FG 7142 (2.5, 5, 10 mg/kg) or BZ receptor agonist chlordiazepoxide (CDP: 5 mg/kg) on the switch-off latency, i.e., the time elapsed between the onset of the stimulation and its offset by a press of the bar. It was found that FG 7142 decreased, whereas CDP increased the mean switch-off latency for electrical stimulation of the PAG, which is interpreted as a potentiating effect of FG 7142 and a reducing effect of CDP on the electrically induced aversive state. By contrast, neither FG 7142 nor CDP were found to affect the mean switch-off latency for MLR stimulations. These results suggest a difference in the pharmacological sensitivity to BZ receptor ligands between aversive states elicited by electrical stimulation of the PAG or MLR.

Animals↗

PubMed1990

Treadmill locomotion and aversive effects induced by electrical stimulation of the mesencephalic locomotor region in the rat.

The effects of electrical stimulation of the "mesencephalic locomotor region" and adjacent dorsolateral tegmentum were assessed and compared in the same rats in freely moving conditions or when lightly anesthetized and suspended over a moving treadmill. In freely moving conditions, electrical brain stimulation (EBS) of this part of the mesencephalon elicited mainly aversive effects (escape reactions: violent running and explosive jumps), but also ipsiversive circling and "gnawing." On the treadmill, EBS induced flexions of hindlimbs followed by locomotion (stepping) or flexions only. In addition, it was found that locomotion and flexions on the treadmill were almost exclusively elicited by EBS of sites positive for escape reactions in freely moving conditions.

Animals↗

PubMed1989

Conditioned place aversion produced by microinjections of semicarbazide into the periaqueductal gray of the rat.

Previous studies have shown that the blockade of GABA-ergic neurotransmission in the periaqueductal gray (PAG) of the rat induce flight reactions. The present study examined whether a negative affective state was produced by such a blockade. Microinjections of semicarbazide, a GABA synthesis inhibitor, into the PAG were found to produce a conditioned place aversion. In a second experiment, it was found that the potent GABA agonist muscimol antagonized the effects of semicarbazide, without producing a conditioned place preference or aversion by itself. These results suggest that the blockade of the tonic inhibition exerted by GABAergic terminals in the PAG results in both an aversive experience and an overt flight reaction.

Animals↗

PubMed1989

Conditioned place aversion produced by FG 7142 is attenuated by haloperidol.

A place conditioning paradigm was used to examine the affective properties of FG 7142, a benzodiazepine receptor inverse agonist. At the highest dose tested (10 mg/kg, IP), FG 7142 produced a significant place aversion to the drug-paired compartment. In a second experiment, haloperidol injections were given before FG 7142. It was found that haloperidol (0.2 mg/kg) significantly reduced the measured conditioned place aversion produced by FG 7142, without exhibiting any aversive or rewarding effects by itself. These results suggest that dopamine receptors are involved in the learning or expression of conditioned place aversion induced by benzodiazepine receptor inverse agonists.

Animals↗

PubMed1989

Effects of unilateral microinjections of GABAergic drugs into the inferior colliculus on auditory evoked potentials and on audiogenic seizure susceptibility.

Alteration of GABAergic neurotransmission within the inferior colliculus (IC) appears to be involved in the generation of the audiogenic seizure (AGS) susceptibility. In the present study, we provide evidence indicating that this susceptibility may result from IC neuronal hyperexcitability to sound induced by a decreased GABAergic inhibition. In a first experiment, a unilateral microinjection of bicuculline, a GABAa antagonist, into the IC of normal rats increased the amplitude of the collicular auditory evoked potential, while the microinjection of THIP, a GABAa agonist, decreased this response. In a second experiment, a unilateral microinjection of bicuculline into the IC induced AGS susceptibility in normal rats.

Acoustic Stimulation↗

PubMed1989

[The extent and quality of intensive therapy measures in psychiatry].

An epidemiological study considered all new admissions that were the subject of intensive therapy in three Leipzig clinics from October 1, 1983 to September 30, 1984, comparing them with a randomly selected control group. From a total of 1,928 admissions, 314 underwent intensive therapy, 46 of these under the intensive therapist (anesthetist, internist, surgeon). Indications arising out of intensive medicine resulted in the transfer of 1.2% of all admissions to other institutions. Extent and quality of the intensive measures was in general judged to be good.

Adolescent↗

PubMed1987

Spike trains in rat periaqueductal gray depend on the stochastic properties of interacting electrical stimulation trains.

Spike trains flowing into the periaqueductal gray (PAG) might be discriminated from one another by PAG neurons on the basis of the distribution or sequence of their respective interspike intervals. The various sequences of interspike intervals characteristic of spontaneous PAG unit activities were assessed in a preliminary experiment. These sequences were then simulated by means of appropriate mathematical functions. These functions allowed the production of stimulation trains that were applied to two PAG sites to induce spike trains with similar sequences in order to reveal the sensitivity of PAG neurons to the stochastic structure of afferent spike trains. We placed emphasis on parameters of the spike train that proved to be altered independently of any alteration of the corresponding parameters in the stimulation train. The mean pulse rate is the simplest example of such a parameter as it was never altered in the stimulation train. Alterations of either the distribution or sequence of pulses in the stimulation train were found to affect the mean discharge rate in a number of cases (30-40% of the cases). Despite their moderate degree (20-30% mean rate alteration) such differential effects could correspond to stimulation-induced differential behavioral effects as was shown in a previous study. Furthermore, a specific dependence of the generated spike trains on the sequential structure of the stimulation train was observed in some cases when appropriate stimulation trains were simultaneously applied to another PAG stimulation site. This fact is worth considering in relation to the integrative function of the PAG neuronal network.

Action Potentials↗

PubMed1987

Mapping of jumping, rearing, squealing and switch-off behaviors elicited by periaqueductal gray stimulation in the rat.

Rats readily learn to escape from a stimulation applied to most mesencephalic periaqueductal gray (PAG) sites. In the present study, we tried to find out to what extent the differential effects induced by such stimulations actually reflect the existence of intraPAG functional subdivisions. To that end, a row of five electrodes was implanted into the PAG of each of 29 rats. Two kinds of effects were analyzed, the stimulation-elicited overt behaviors and the generalization of switch-off responding from one stimulation site to the others. Further, switch-off latency versus interpulse interval (IPI) relationships were established and both the threshold IPIs and the ceiling switch-off latencies were determined. The most commonly elicited behaviors (jumping, rearing and squealing) as well as the threshold IPIs and the ceiling switch-off latencies were mapped within the PAG. Switch-off behavior was elicited from all the stimulation sites studied. However, in the dorsal PAG the switch-off latency was found to decrease more steeply with decreasing IPI than it did in the ventral PAG. Switch-off generalization was less frequently observed between dorsally located stimulation sites. Jumps were most often elicited from dorsally and rostrally located PAG sites while squeals were more frequently elicited from the caudal part of the PAG and rearings from PAG subareas surrounding the aqueduct.

Animals↗

PubMed1986

Unit activity alterations induced in the mesencephalic periaqueductal gray by local electrical stimulation.

In the framework of a series of investigations concerning the neural substrate of aversion, electrophysiological methods were used in order to specify, within the rat's periaqueductal gray (PAG), functional properties, viz. conduction velocity and refractory period, of PAG neurons already assessed in previous studies by means of behavioral methods, and to gather data on their local synaptic relationships. Unit activities were recorded from the periaqueductal gray with the aim of analyzing those alterations that would be induced by locally applying an electrical stimulation with parameters shown to elicit escape behavior. An implanted row of electrodes allowed the application of a stimulation to several sites aligned along a mediolateral or a rostrocaudal axis through the periaqueductal gray. The results indicate that an electrical stimulation applied to the periaqueductal gray may induce its effects through the activation of a number of dendrites and many slow conducting fibers running in a great variety of directions and branching within the periaqueductal gray. Their refractory period was surprisingly low (0.6 ms) for slow conducting fibers (below 1 m/s). The local circuitry appears to include many inhibitory connections. Their organization is assumed to be partly recurrent. Stimulation-induced inhibition becomes predominant when the stimulation is moved away from the recorded neuron along the mediolateral axis, but not along the rostrocaudal axis.

Animals↗