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B W Peeters

Publications and source records attributed to B W Peeters.

At least 19 recordsLinked to original sources
PubMed1997

Control conditions in the fear-potentiated startle response paradigm.

In the present study, the fear-potentiated startle response paradigm was modified in order to investigate the decrease in control startle levels often observed after administration of anxiolytic drugs. The within-animal comparison of control startle amplitudes and fear-potentiated startle amplitudes normally used was replaced by a between-animal comparison. Moreover, the experimental design was extended with an additional control group, a no-shock group. The anxiolytics diazepam and chlordiazepoxide were used as pharmacological tools. The main findings were that both benzodiazepines dose-dependently reduced control startle amplitudes and no-shock startle amplitudes equally, suggesting that shock-associated contextual cues are not responsible for the drug-induced decrease in control startle amplitudes in the fear-potentiated startle response paradigm.

Animals↗
PubMed1996

Modulation of 5-HT receptor subtype-mediated behaviours by corticosterone.

Malfunction of the serotonergic system and dysregulation of the hypothalamo-pituitary-adrenocortical axis have been implicated in the pathophysiology of depression. Several studies provide evidence for reciprocal influences between glucocorticoids and 5-HT receptors. The effect of repeated treatment with a high dose of corticosterone (50 mg/kg s.c. twice daily for 4 days) on 5-HT receptor subtype-mediated behaviours was studied. It was found that in rats that were repeatedly treated with corticosterone the number of 2-chloro-6-(1-piperazinyl)pyrazine HCl (MK 212)-induced, 5-HT2C receptor-mediated penile erections were reduced, whereas both MK 212 and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced 5-HT2A receptor-mediated head shakes were increased. The (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced lower lip retraction mediated by presynaptic 5-HT1A receptors was unchanged, whereas the open field activity induced by 8-OH-DPAT was enhanced in corticosterone pretreated rats. These changes in 5-HT receptor subtype-mediated behaviours were not seen after a single injection with corticosterone given 24 h or 5 days before. The results suggest that 5-HT2A, 5-HT2C and postsynaptic 5-HT1A receptor-mediated behaviour can be modulated by repeated treatment with a high dose of corticosterone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Fear-potentiated startle response is remarkably similar in two laboratories.

The fear-potentiated startle response paradigm is used to investigate anxiolytic properties of drugs. The first objective of the present study was to further investigate the predictive validity of this paradigm. The anxiolytics chlordiazepoxide (2.5-10 mg/ kg IP) and oxazepam (1-10 mg/kg PO) and the putative anxiolytic flesinoxan (1-10 mg/kg PO) decreased startle potentiation dose-dependently, indicating an anxiolytic effect. The antidepressant fluvoxamine (5-20 mg/kg PO) did not affect startle potentiation. Ideally, anxiolytic drugs attenuate startle potentiation without affecting control startle levels, although some studies report altered control startle amplitudes. The second objective was to investigate whether different effects on control startle amplitudes are related to different startle devices. Therefore, the drugs were tested in two laboratories. Results showed no significant differences between laboratories, indicating that equipment is not a critical factor in the drug-induced alteration of control startle levels. In an additional experiment, it was shown that flesinoxan (10 mg/kg PO) did not affect strychnine-induced startle potentiation, supporting the idea that the attenuating effect of flesinoxan on the fear-potentiated startle response is due to its anxiolytic properties. Thus, the fear-potentiated startle response paradigm appears a valid and reliable model for anxiolytic properties of drugs.

Animals↗
PubMed1995

Changes in prepulse inhibition after local administration of NMDA receptor ligands in the core region of the rat nucleus accumbens.

The dopamine and glutamate hypotheses are two pharmacological models for schizophrenia. In the present investigations, the prepulse inhibition paradigm was used to evaluate the role of the nucleus accumbens core region in both models. Prepulse inhibition is known to be decreased in schizophrenics, when compared with control patients, and in rats after systemic injection of dopamine receptor agonists and non-competitive antagonists of the NMDA receptor. In the present study injection of dopamine in the rat nucleus accumbens core region also decreased prepulse inhibition. Injections of NMDA decreased, whereas a low dose of the competitive NMDA receptor antagonist (+/-)-2-amino-5-phosphonopentanoic acid (AP-5) and the non-competitive NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydroxy-5H-dibenzo[a,d]cyclohepten-5 ,10-imine hydrogen maleate (MK-801) increased prepulse inhibition. The results indicate an involvement of the accumbens core in mediating the systemic effects on prepulse inhibition of dopamine receptor agonists but not of non-competitive NMDA receptor antagonists.

2-Amino-5-phosphonovalerate↗
PubMed1994

Effects of acoustic prepulses on the startle reflex in rats: a parametric analysis.

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can either inhibit or facilitate the startle reaction. To investigate this apparent discrepancy, a number of characteristics of the acoustic prepulse were varied and the effects on the startle reaction were studied. The results showed that increasing the intensity of the prepulse (81-85 dB) resulted in an increased inhibition and could even turn facilitation into inhibition (at 3-13 ms prepulse-startle interval). Varying prepulse lengths (1-45 ms) did not change the observed startle modification. Only when the prepulse offset was close to the startle onset, changes could be observed. Confronting the animal with the same test session for several days resulted in increased inhibition and a change from facilitation to inhibition (at 3-13 ms prepulse-startle interval). The results demonstrate that the characteristics of the prepulse determine its effect on the startle reaction. An hypothetical model is proposed which might explain the observed data.

Acoustic Stimulation↗
PubMed1994

Effects of acoustic prepulses on the startle reflex in rats: a parametric analysis.

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can either inhibit or facilitate the startle reaction. To investigate this apparent discrepancy, a number of characteristics of the acoustic prepulse were varied and the effects on the startle reaction were studied. The results showed that increasing the intensity of the prepulse (81-85 dB) resulted in an increased inhibition and could even turn facilitation into inhibition (at 3-13 ms prepulse-startle interval). Varying prepulse lengths (1-45 ms) did not change the observed startle modification. Only when the prepulse offset was close to the startle onset, changes could be observed. Confronting the animal with the same test session for several days resulted in increased inhibition and a change from facilitation to inhibition (at 3-13 ms prepulse-startle interval). The results demonstrate that the characteristics of the prepulse determine its effect on the startle reaction. An hypothetical model is proposed which might explain the observed data.

Acoustic Stimulation↗
PubMed1994

Acoustic prepulses can facilitate the startle reflex in rats: discrepancy between rat and human data resolved.

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can inhibit or facilitate the startle reaction. Previous studies reported that at large intervals between prepulse and startle stimulus the prepulse facilitates the startle reaction, possibly by means of an orienting response. This was, however, only observed in humans and not in rats, and was consequently proposed to measure unique brain functions. In the present study with rats, the prepulse intensity was decreased from 85 to 81 dB, which resulted in decreased prepulse inhibition. Prepulse facilitation was now observed at large intervals (> 800 ms), which suggests that this facilitation was masked by inhibition in previous studies. These results solve the discrepancy between rat and human data and indicate that similar mechanisms are involved.

Acoustic Stimulation↗
PubMed1994

The WAG/Rij rat model for nonconvulsive absence epilepsy: involvement of nonNMDA receptors.

The involvement of AMPA and kainate receptors in nonconvulsive epilepsy was studied by intracerebroventricular injections of AMPA, GDEE, kainic acid and kynurenic acid in WAG/Rij rats. The WAG/Rij rat strain is recognized as an animal model for human absence epilepsy. EEG registrations showed that AMPA (0.1 pmol/5 microliters; 1 pmol/5 microliters; 10 pmol/5 microliters) dose-dependently increased the nonconvulsive absence epilepsy while GDEE (0.2 mumol/5 microliters; 1 mumol/5 microliters; 5 umol/5 microliters) caused a dose-dependent decrease. All effects of GDEE could be blocked by an inactive AMPA dosage. Kainic acid (0.01 nmol/5 microliters; 0.1 nmol/5 microliters; 0.15 nmol/5 microliters) had no effects on the nonconvulsive epilepsy but induced convulsions in the two highest dosages. Kynurenic acid (50 nmol/5 microliters; 100 nmol/5 microliters; 500 nmol/5 microliters) decreased dose-dependently the incidence of nonconvulsive epilepsy. The effect of kynurenic acid could be blocked by a nonconvulsive dosage of kainic acid. These results show that the AMPA and kainate receptor appear to be involved in nonconvulsive epilepsy. Furthermore, blockage of these two receptor subtypes led to an antiepileptic effect without inducing behavioural alterations. Therefore, selective AMPA and kainate receptor antagonists might be potent anti-epileptics.

Animals↗
PubMed1994

Interactions between NMDA and nonNMDA receptors in nonconvulsive epilepsy in the WAG/Rij inbred strain.

The interaction between NMDA and nonNMDA receptors was studied in nonconvulsive epilepsy in WAG/Rij rats. Compounds acting on NMDA (NMDA, APH) and nonNMDA (AMPA, GDEE, kainic acid, kynurenic acid) receptors were coinjected intracerebroventricularly. The WAG/Rij rat strain may be an animal model for human nonconvulsive absence epilepsy. The effects on the epilepsy, EEG and behaviour were measured. It appeared that the epilepsy increase, induced by the nonNMDA receptor agonist AMPA, and in a less obvious way, kainic acid, was blocked by the NMDA receptor antagonist APH. The effects of NMDA were completely blocked by the nonNMDA receptor antagonists GDEE and kynurenic acid. These results suggest that there is an interaction between NMDA and nonNMDA receptors. It might be that nonNMDAergic compounds act via activation or inactivation of NMDA receptors and that this latter receptor subtype is the trigger for an epileptic seizure.

Animals↗
PubMed1994

Involvement of corticosteroids in the processing of stressful life-events. A possible implication for the development of depression.

In a sub-population of endogenously depressed patients, disturbances of the hypothalamic-pituitary-adrenal axis can be observed. Increased cortisol and CRH levels combined with normal ACTH concentrations have often been reported. Corticosteroids appear to play a role in the mood changes, in depressed subjects. However, their mechanism of action is unknown. In animal experiments, the involvement of corticosteroids in stressor-induced learning was investigated. Three paradigms were used. In the Porsolt swimtest an animal had to learn to adapt to an inescapable situation. In the lithium chloride conditioned taste aversion an animal learned to avoid sugar water. In the amphetamine sensitization a second injection of amphetamine caused a potentiated response, because of conditioning. All three conditions appeared to be stressful because they induced a corticosterone release. When adrenalectomized (ADX) mice were compared to control animals it appeared that, in all three paradigms, their memory function was disturbed. The data indicated that this was a specific glucocorticoid-mediated effect since corticosterone and dexamethasone injections were able to reverse the ADX-induced deficit. The ADX-induced disturbances were only observable at moderate stress levels. More severe stressors (lower water temperature in the Porsolt swimtest, higher lithium chloride and amphetamine doses) also made ADX mice remember their previous experiences. The results suggest that corticosteroids are involved in the consolidation of stressful events and the corresponding coping responses. They play, however, only a role in the case of moderate stressors. In ADX animals no stressor-induced corticosterone increase can occur and therefore these animals only remember severe stressors. In a depressed patient basal steroid levels are increased and consequently very mild stressors, which induce only a small extra steroid release, will be remembered. The remembering of all these negative experiences might be of importance for the development and maintenance of the depression.

Adrenal Cortex Hormones↗
PubMed1993

Stimulus characterization of estradiol applying a crossfamiliarization taste aversion procedure in female mice.

In female mice (n = 240), the estradiol stimulus was characterized by studying preexposure effects of sex steroids and sickness-inducing drugs on estradiol-induced (50 micrograms/kg SC) conditioned taste aversion (CTA). It was established that preexposure to estradiol itself (2-50 micrograms/kg SC) attenuates the development of CTA produced by the hormone. Only partial crossfamiliarization effects were found with progesterone (50-200 micrograms/kg SC) and testosterone (250-1000 micrograms/kg SC), steroids that induce CTA themselves. Preexposure to the sickness-inducing drugs lithium chloride (22 mg/kg SC) and apomorphine (0.1-0.2 mg/kg SC) prevented or substantially reduced the development of estradiol-induced CTA, respectively. It was concluded that only a low degree of stimulus resemblance exists between estradiol and the other principal sex steroids, progesterone and testosterone. In addition, it was concluded that the estradiol stimulus resembles the stimuli produced by sickness-inducing drugs.

Animals↗
PubMed1992

Enhancement of regeneration by Org 2766 after nerve crush depends on the type of neural injury.

The neurotrophic effects of the adrenocorticotropin (ACTH)-(4-9) analog Org 2766 (Met(O2)-Glu-His-Phe-D-Lys-Phe) were studied in rats recovering from a sciatic nerve crush. Org 2766 (10 micrograms/rat s.c., every 48 h) increased the number of myelinated axons reinnervating a previously denervated sciatic nerve by 32% (P less than 0.01), as assessed 13 days after crush lesioning, and facilitated recovery of sensorimotor functioning by 14% (P = 0.05), as measured by foot withdrawal after stimulation of the footsole with hot air. However, these facilitating effects were only seen if the nerve was lesioned using forceps with grooved jaws and not if forceps were used with cross-hatched jaws. Endoneural tubes and Schwann cells of the sciatic nerve appeared to be better preserved after crushing with grooved rather than cross-hatched jaws. Our data indicate that the regeneration-enhancing effects of Org 2766 are dependent on the type of injury applied to the endoneurium and endoneural tubes of the sciatic nerve and suggest that endoneural tissue may mediate the neurotrophic properties of Org 2766.

Adrenocorticotropic Hormone↗
PubMed1992

Differences in spike-wave discharges in two rat selection lines characterized by opposite dopaminergic activities.

In the present study, 48 h electroencephalographic recordings were made in order to examine the incidence and duration of spike-wave discharges in apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) lines of an outbred strain of Wistar rats. In comparison with APO-UNSUS rats APO-SUS rats showed significantly more spike-wave discharges, especially during the dark period: both the mesor and the amplitude of the optimal cosine fitted to the data were significantly increased, whereas neither the acrophase nor the period length (24 h) differed. It is suggested that both the relatively low dopaminergic activity of the nigrostriatal fibres and the relatively high dopaminergic activity of the mesolimbic fibres, i.e. two well characterized features of the APO-SUS rats, significantly contribute to the high incidence of spike-wave discharges in these APO-SUS rats.

Animals↗
PubMed1992

Genetics of spike-wave discharges in the electroencephalogram (EEG) of the WAG/Rij inbred rat strain: a classical mendelian crossbreeding study.

The WAG inbred strain might be an animal model for human absence epilepsy. To study the inheritance pattern of absence epilepsy, WAG rats were crossbred, in a classical Mendelian way, with inbred ACI rats which show no signs of epilepsy. In the parental strains, reciprocal F1 hybrids, F2, B1, and B2 generations, the number and duration of spike-wave discharges were determined. One hundred percent of the F1 animals showed spike-wave discharges, while the percentages for the F2, B1, and B2 generations were 79, 95, and 37%, respectively. These results suggest that the occurrence of spike-wave discharges is determined by one gene with a dominant mode of inheritance. Cavalli's least-squares fitting procedure suggested different genetic models for the two parameters (number and duration) during the two periods (dark and light). These results confirm our previous findings (Peeters et al., Behav. Genet. 20, 453-460, 1990) that a number of genes are involved in absence epilepsy. One dominant gene appears to determine the occurrence, however, while others manipulate the number and duration of epileptic phenomena during the two periods dark and light.

Animals↗
PubMed1992

The involvement of glucocorticoids in the acquired immobility response is dependent on the water temperature.

The Porsolt swim test was used to study the role of glucocorticoids in a simple learning paradigm. Two experiments were performed. In the first experiment, the stressfulness of the situation was manipulated by testing control, sham-operated and adrenalectomized mice at different water temperatures (20 degrees C, 25 degrees C, 30 degrees C and 35 degrees C). In the second experiment, control mice were injected with the glucocorticoid antagonist RU38486 (3.2 mg/kg, 10 mg/kg, 32 mg/kg); adrenalectomized mice were injected with the glucocorticoid agonists corticosterone (0.46 mg/kg, 1.0 mg/kg, 2.2 mg/kg) and dexamethasone (0.005 mg/kg, 0.05 mg/kg, 0.1 mg/kg). The results show that water temperature is a very important factor in the Porsolt swim test. It influences the overall behaviour of the animals and changes the involvement of glucocorticoids. At a water temperature of 25 degrees C, glucocorticoids play an important role in the retention of the immobility response; ADX mice are impaired, and this impairment can be ameliorated by corticosterone and dexamethasone injection. Furthermore, the impairment can be induced in control mice by RU38486. The effects observed at 25 degrees C were, however, not observable at 20 degrees C, 30 degrees C and 35 degrees C, which suggests, contrary to previous reports, that glucocorticoids do not play a universal role in retention processes.

Adrenal Glands↗
PubMed1992

Sex steroids possess distinct stimulus properties in female and male mice.

Very few studies have investigated the aversive properties of sex steroids in animals. We studied these properties by testing oestradiol-3-benzoate, testosterone-propionate and progesterone in a conditioned taste aversion set-up, in intact female and male mice. Oestradiol-3-benzoate induced a taste aversion in both female and male mice; however, testosterone-propionate and progesterone had an effect only in females. These results show that sex steroids have intrinsic aversive properties. The different effects of the steroids in males and females cannot simply be explained by nausea induction or novelty.

Analysis of Variance↗