Biomedical subjects

J L Slangen

Publications and source records attributed to J L Slangen.

At least 37 records · Page 2Linked to original sources

PubMed1992

Intracerebroventricular LHRH may serve as a discriminative stimulus in male rats.

Male Wistar rats (N = 16) were trained to discriminate 5 micrograms/kg LHRH, injected intraperitoneally, from saline in a two-lever, food-reinforced drug discrimination procedure, with an injection-session interval of 45 min. Reliable discrimination of LHRH was acquired within 60 training sessions. Subsequent generalization tests in brain-cannulated animals showed dose-dependent and time-related partial substitution of intracerebroventricular LHRH for intraperitoneal LHRH (ventricle doses ranged from 25-400 ng, and the injection-session intervals ranged from 10-40 min). These results indicate that centrally administered LHRH may serve as a dose- and time-dependent discriminative stimulus in male rats.

Animals↗

PubMed1992

Dose-dependent and time-related stimulus properties of LHRH in male but not in female rats.

Male and female rats (N = 32) were trained to discriminate 5 micrograms/kg LHRH from saline in a two-lever, food-reinforced drug discrimination procedure with injection-session intervals of 15 min or 45 min. When the interval was 15 min, neither males nor females were able to discriminate the stimulus conditions. With an interval of 45 min, LHRH showed sex-dependent stimulus properties. Male, but not female, rats reliably discriminated LHRH from saline within 50 training sessions. In males, generalization tests showed dose-dependent and time-related stimulus effects of LHRH (doses ranged from 62.5 ng/kg to 8 micrograms/kg, and intervals ranged from -15 min to -120 min). The results indicate that LHRH may be an essential part of the stimulus complex in male rats but could not gain control over operant behavior in female rats.

Animals↗

PubMed1992

Discriminative stimulus properties of the serotonergic compound eltoprazine.

The 5-hydroxytryptamine-1a/1b (5-HT1a/1b) agonist eltoprazine is the main representative of the so-called "serenics," a group of drugs sharing a specific antiaggressive activity. Rats were trained to discriminate an i.p. dose of 0.5 mg/kg of eltoprazine from saline in a two-lever operant drug discrimination task using a fixed ratio 10 schedule of food reinforcement. The cue of eltoprazine was found to be dose and time dependent. The eltoprazine stimulus generalized to the structurally related experimental drug fluprazine, the mixed 5-HT1a/1b agonist 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)-1H indole, (RU 24969), the 5-HT1b/1c agonist 1-[3-(trifluoromethyl)phenyl]piperazine, (TFMPP), the 5-HT1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin-HB, (8-OH-DPAT), and the beta adrenergic/5-HT1 antagonists (+/-)-pindolol and (+/-)-propranolol. The eltoprazine cue partially generalized to the cues of the 5-HT1a agonists flesinoxan and buspirone, (m-CPP), the 5-HT1b/1c agonist 1,3-chlorophenyl-piperazine dihydrochloride and the 5-HT1c/2 antagonist mesulergine, and did not generalize to the 5-HT2/1c agonist DOI. During tests of antagonism, neither mesulergine, the nonspecific 5-HT antagonist methysergide, the 5-HT2 antagonist ketanserin, the 5-HT3 antagonist tropisetron (ICS 205-930), nor (+/-)-pindolol and (+/-)-propranolol attenuated the stimulus effect of eltoprazine. The specific beta adrenergic antagonist timolol did not substitute for eltoprazine. The present data show that eltoprazine can serve as a discriminative stimulus in rats and suggest that specifically 5-HT1 (i.e., 5-HT1a and 5-HT1b) receptors are involved in the stimulus properties of eltoprazine.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1991

Effects of subchronic d-amphetamine on prepulse and gap inhibition of the acoustic startle reflex in rats.

Prepulse inhibition of the startle reflex has been used as an animal model for information processing deficits found in some types of schizophrenia. These deficits may be mediated by hypersensitive dopaminergic systems. In the present study, the effects of subchronic d-amphetamine administration [2 mg/kg intraperitoneally (IP)] on prepulse and gap inhibition of the startle reflex were compared to the effects of acute amphetamine and saline administration on startle inhibition. Results of three experiments are reported. The first two experiments were used to select prestimulus parameters sensitive to changes in stimulus intensity on the one hand, and prestimulus parameters sensitive to temporal aspects of stimulus processing on the other hand. Because schizophrenics have problems with the temporal sequencing of information, prestimulus inhibition of the startle reflex was expected to be more pronounced when prestimulus processing depended predominantly upon temporal factors. Results supported this hypothesis, although the effects of d-amphetamine were found at near detection threshold duration only. Subchronic amphetamine had no effect on the neuronal mechanisms underlying inhibition of the startle reflex by prestimuli. The results also suggested that a careful selection of duration and intensity of the prestimulus may increase the sensitivity of the prestimulus-startle paradigm for the effects of drugs, for example.

Acoustic Stimulation↗

PubMed1991

Abnormal visual event-related potentials of autistic children.

This study compared the visual ERPs and concurrently measured fixation times of autistic children with those of normal children and two psychiatric control groups (so-called "externalizers" and "internalizers"). Autistic children had, in contrast with normal control groups, smaller P3 waves (occipital maximum) to visual target stimuli but did not differ in this respect from the two psychiatric control groups. When the autistic group was split into "good" and "bad" performers, the latter group had significantly smaller amplitudes than the former. No difference was found between the groups in electrophysiological reactivity to the first, novel stimulus of a habituation series. However, an unexpected change in stimulus location induced an increased Fz N400 in the normal group but not in the autistic group or the two psychiatric control groups. In addition, in a non-task-relevant habituation condition, the autistic group fixated complex visual stimuli for shorter times and had smaller occipital P3 waves than the control groups. Analysis of covariance showed that the smaller P3s could not be explained by the shorter fixation times. In none of the ERP parameters were there differences in habituation rate between the controls and the autistic children.

Arousal↗

PubMed1991

Estradiol-induced conditioned taste aversion and place aversion in rats: sex- and dose-dependent effects.

Effects of various doses (0-250 micrograms/kg, SC) of estradiol-17 beta (E2) in a two-bottle choice conditioned taste aversion and a two-compartment conditioned place preference procedure were studied in male and female rats. Dose-dependent taste aversion and place aversion effects of E2 were established, and the conditioned taste aversion procedure was found to be more sensitive in detecting aversive properties of E2 than the conditioned place preference procedure. Although aversive properties of E2 were found in both sexes, the effects were clearly more prominent in males as compared to females. From this study, it was concluded that E2 acts as an unconditioned aversive stimulus in both male and female rats capable of gaining control over different types of behavior by associative learning.

Animals↗

PubMed1991

Effects of anxiety drugs on the modification of the acoustic startle reflex by noise gaps.

The acoustic startle reflex was modified by presenting gaps (0-30 ms) in a continuous noise (70 dB) before the startle eliciting stimulus. The effects of midazolam (0.4-1.8 mg/kg, IP), DMCM (0.1-0.4 mg/kg, IP), buspirone (5-20 mg/kg, PO), 8-OH-DPAT (0.5-8 mg/kg, IP), and clonidine (0.009-0.08 mg/kg, IP) on startle amplitudes (reflecting sensorimotor reactivity) on the one hand, and on gap inhibition of the startle reflex (a measure of temporal acuity) on the other hand, were investigated. The results showed that midazolam and clonidine attenuated sensorimotor reactivity dose-dependently. DMCM had no systematic effect on sensorimotor reactivity. Buspirone and 8-OH-DPAT increased sensorimotor reactivity dose dependently. Furthermore, midazolam and clonidine did not affect the neuronal systems underlying inhibition of the startle reflex. In contrast, DMCM and buspirone increased inhibition dose-dependently, and 8-OH-DPAT first increased and then decreased inhibition of the startle reflex. The possibility that drug-induced behavior affected the startle reflex was discussed.

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

PubMed1991

Effects of buspirone and chlordiazepoxide on plasma catecholamine and corticosterone levels in stressed and nonstressed rats.

The effects of intragastric administration of the prototypical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-elevated plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) contents were investigated. Acute dosing of CDP (1-27 mg/kg) produced dose-related increases in basal CS secretion but was without effect on basal NA levels. The high dose of CDP caused a slight short-term A increase. Dose-dependent increases in plasma A, NA and CS contents were observed after acute treatment with BUSP (2 and 20 mg/kg). A medium dose of CDP (9 mg/kg) attenuated the stress-induced CS and A elevations. High doses of CDP that elevated basal CS release prevented a further increase of CS by stress and inhibited the NA and A response to stress. BUSP (2 and 20 mg/kg) was not effective in decreasing the stress-elicited rise of CS, NA or A. Conversely, the 20 mg/kg dose of BUSP enhanced the stress-induced A response. Repeated administration of CDP (9 mg/kg/day for six days) produced tolerance to the elevation of basal CS triggered by acute CDP treatment, but increased the efficacy of the drug's CS and A attenuating action in stressed rats. Repeated administration of BUSP (2 mg/kg/day for six days) also produced tolerance to the acute BUSP-induced effect on basal CS release, but did not affect the stress-induced CS, NA and A responses. It is concluded that the clinically effective anxiolytic BUSP does not have the BDZ-like property to inhibit stress-induced elevations in CS, NA and A. Furthermore, the present data support other evidence that activation of 5-HT1A receptor mechanisms increases plasma catecholamine and corticosterone concentrations.

Animals↗

PubMed1991

The pentylenetetrazole-cue antagonist actions of bretazenil (Ro 16-6028) as compared to midazolam.

In order to compare the potencies of bretazenil (Ro 16-6028) and midazolam (MDZ) to antagonize the pentylenetetrazole (PTZ) cue, rats were trained to discriminate between 15 mg/kg IP PTZ and saline (FR10, food reinforced). Additionally, other rats were trained to discriminate between 1.0 mg/kg IP MDZ and saline in order to investigate the degree of generalization of bretazenil to MDZ, and to test for the antagonizing effects of PTZ. Both bretazenil and MDZ were able to block the PTZ cue. Bretazenil was about 60 times more potent than MDZ in this respect. In tests for response generalization, bretazenil substituted for MDZ cue. Bretazenil did not show MDZ-antagonist actions. PTZ did block the MDZ cue and the generalization of bretazenil in the MDZ-trained animals. Assuming that the drug discriminative stimulus functions of PTZ are closely related to its anxiogenic effects, it was concluded that bretazenil may possess powerful anxiolytic properties. Bretazenil did not suppress the response rates which is consistent with previous studies reporting a lack of sedative and muscle-relaxant effects of bretazenil.

Animals↗

PubMed1991

Luteinizing hormone releasing hormone-induced conditioned place-preference in male rats.

Conditioned place-preference induced by intraperitoneal injections of luteinizing hormone releasing hormone (LHRH) was studied in male rats. In Experiment 1, dose-dependent effects (doses: 0, 0.2, 1 and 5 micrograms/kg) were observed in gonadectomized males provided with a subcutaneous silastic implant containing testosterone. Animals injected with 1 or 5 micrograms LHRH developed reliable preference for the LHRH-associated compartment of a two-compartment preference box. The 0 and 0.2 microgram doses were without effect. Experiment 2 further studied the place-preference effects induced by 5 micrograms LHRH, by varying the sex steroid baseline condition of the animals. A significant effect of LHRH on place-preference was found in gonadectomized males with a testosterone or estradiol implant and in gonadally intact males. Differences between these groups were not found. However, in gonadectomized males without steroid substitution, LHRH did not induce place-preference. These data indicate that rewarding properties related to LHRH treatment can be observed in male rats, provided that the males are additionally exposed to sufficient levels of circulating sex steroids.

Animals↗

PubMed1991

Effects of chlordiazepoxide, flumazenil and DMCM on plasma catecholamine and corticosterone concentrations in rats.

The effects of drugs representing three classes of benzodiazepine (BDZ) receptor-acting agents on circulating corticosterone (CS), noradrenaline (NA) and adrenaline (A) were examined in unstressed rats. Intragastric administration of a single-dose of the inverse agonist 3-carbomethoxy-4-ethyl-6,7-dimethoxy-beta-carboline (DMCM; 10 mg/kg) evoked 15-, 4- and 1.5-fold increases in plasma CS, A and NA, respectively, as compared to control values. The DMCM-induced CS, A and NA rises were completely blocked by combined treatment with the BDZ antagonist flumazenil (Ro 15-1788; 20 mg/kg). Flumazenil given alone did not affect plasma hormone levels. Administration (either intragastrically or intraperitoneally) of a single-dose of the BDZ agonist chlordiazepoxide (CDP; 20 mg/kg) produced a 10- to 15-fold increase in plasma CS but caused no change in plasma NA and A contents. Pretreatment with flumazenil blocked the CDP-elicited release of CS. The findings indicate that the CNS mechanisms controlling pituitary-adrenocortical and sympatho-adrenal outflow under basal conditions are functionally linked to central-type BDZ receptor system(s). Drugs with agonist or inverse-agonist actions at these receptor sites can be differentiated from each other by their distinct effects on plasma NA and A, but not CS, release.

Animals↗

PubMed1991

Abnormal electrodermal reactivity to novel visual stimuli in autistic children.

Skin conductance responses and eye-fixation behavior to visual stimuli were measured in high-functioning autistic children, normal children, children with externalizing disorders, and children with internalizing disorders. Novelty, complexity, and subjective significance of the stimuli were manipulated. Autistic children were electrodermally hyporesponsive to novel stimuli. In all groups, manipulation of stimulus complexity only influenced fixation time. Manipulation of subjective significance influenced fixation time as well as skin conductance response in all groups. In the autistic group, adding subjective significance to a stimulus changed electrodermal nonresponders into responders, indicating that nonresponsiveness or hyporesponsiveness in autistic children does not imply a loss of (novel) stimulus detection, filtering, or orientation reaction capability, per se.

Arousal↗

PubMed1991

Removal of the ocular artifact from the EEG: a comparison of time and frequency domain methods with simulated and real data.

Frequency-dependent transfer from EOG to EEG may be insufficiently accounted for by simple time domain regression methods (Gasser, Sroka, & Möcks, 1986; Woestenburg, Verbaten, & Slangen, 1983). In contrast, a multiple-lag time domain regression analysis, using lagged regression of EEG on EOG, must theoretically account for both frequency dependence and independence. Two data sets were constructed, in which the transfer from EOG to EEG was either frequency-independent (constant gain) or frequency-dependent. Subsequently, three different correction methods were applied: 1) a simple regression analysis in the time domain; 2) a multiple-lag regression analysis in the time domain; and 3) a regression analysis in the frequency domain. The major results were that, for data set 1, the three methods constructed the original EEG equally well. With data set 2, reconstruction of the original EEG was achieved reasonably well with the frequency domain method and the time domain multiple-lag method, but not with simple time domain regression. These three correction procedures were also applied to real data, consisting of concomitantly recorded EEG and high-variance EOG series. No appreciable differences in outcome of the three methods were observed, and estimated transfer parameters suggested that these data were marked by weak frequency dependence only, which can be accounted for by simple time domain regression (and also by the other two methods).

Blinking↗

PubMed1990

Characterisation of the discriminative stimulus properties of flumazenil.

Rats were trained to discriminate flumazenil (15 mg/kg i.p.) from vehicle in a two-lever, food-reinforced, operant conditioning procedure. Substitution tests were performed with a wide dose range of flumazenil and of several benzodiazepines and non-benzodiazepine compounds possessing behavioural effects similar to or opposite to those of benzodiazepine agonists. The results indicate that low doses of flumazenil have behavioural effects, that the flumazenil cue has a low degree of specificity and is most strongly related to the stimulus properties of benzodiazepines.

Animals↗

PubMed1990

Extinction and reacquisition of differential responding in rats trained to discriminate between chlordiazepoxide and saline.

In order to assess the resistance of drug discriminative responding to prolonged reinforcement omission, rats were trained to discriminate between either 6.0 mg/kg PO or 30.0 mg/kg PO. CDP and saline, using a food reinforced (V140-FR10) operant procedure. Dose generalization tests were conducted for both groups. Sessions were then run without reinforcement while drug (D) and saline (S) administrations were continued (extinction phase). After a maximum of 30 sessions without reinforcement, or when the rats emitted less than ten responses on either lever during three successive sessions (extinction criterion), reinforcement was reinstated. Finally, additional dose generalization tests with CDP were run. The discriminative responding controlled by the D and S administrations was not affected significantly by prolonged reinforcement omission in either group. For both groups, response rates were decreased and latencies to initiate responding were increased during the extinction phase. Response rate reduction occurred more rapidly for the drug condition in the high training dose group. This group also reached the extinction criterion sooner than the low training dose group. The reacquisition process occurred very rapidly. Response rates increased substantially after the first reinforcement had been obtained. After ten reacquisition sessions, response rates and latencies had reached values similar to those observed before extinction was initiated. Data revealed no differences between groups and the course of reacquisition did not differ between the S and D conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Dynamics of plasma catecholamine and corticosterone concentrations during reinforced and extinguished operant behavior in rats.

Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) concentrations were determined simultaneously in permanently heart-cannulated rats before and during the performance of reinforced and nonreinforced (extinguished) operant behavior. Shortly before the experimental food-reinforced (VI 15-sec schedule) lever-pressing task, anticipatory elevations of plasma NA and CS contents were observed. During reinforced lever responding plasma NA increased, A did not change and CS declined. Extinction was associated with a transient increase in A, decreasing NA and elevated CS concentrations. In addition, a relationship was found between individual lever-pressing rate, neurosympathetic and adrenomedullary reactivity and the degree of schedule-induced polydipsia. The results indicate that presence and absence of expected behavioral consequences (controllability and loss of control, respectively) are attended by selective, but highly dissociated patterns of neurosympathetic, adrenomedullary and adrenocortical output. Collectively, the findings reinforce the concept that distinctive emotional and/or motivational states are associated with different patterns of neuroendocrine responses. The reactivity of the sympathoadrenomedullary component is heavily dependent upon a rat's individual behavioral strategy.

Adrenal Medulla↗

PubMed1990

Plasma catecholamine and corticosterone levels during active and passive shock-prod avoidance behavior in rats: effects of chlordiazepoxide.

Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) concentrations were determined in rats before, during and after 15-min exposure to a constantly electrified (2 mA) or nonelectrified prod which was mounted on the wall of the home cage either with or without bedding material on the floor. Concomitantly, exploration of the prod, freezing and prod-burying behavior were recorded. Both in the presence and absence of bedding material, rats explored the nonelectrified prod and showed a small increase in plasma NA and CS contents. Exploration of the prod was strongly reduced when the prod was electrified. In the presence of bedding material, shocked rats typically displayed burying behavior (active avoidance), whereas in the absence of bedding (i.e., burying option eliminated) shocked rats engaged in freezing behavior (passive avoidance). The passive avoidance situation was accompanied by larger A and CS increases but a lower NA rise as compared to the hormonal responses associated with the active avoidance situation. Administration of the anxiolytic chlordiazepoxide (CDP; 9 mg/kg intragastrically) attenuated the shock-induced suppression of prod exploration, decreased prod-burying behavior but, paradoxically, increased freezing behavior. Irrespective of bedding condition, the prod shock-induced elevations in plasma CS and A contents were completely abolished in CDP-treated rats. The rise in plasma NA was attenuated only in CDP-treated rats tested on a bedding-floor. The results indicate that passive (e.g., freezing) and active (e.g., burying) behavioral coping are each accompanied by specific and dissociated patterns of neurosympathetic, adrenomedullary and adrenocortical outflow. CDP-treatment shifts an animal's behavioral coping style from an active to a passive form of avoidance responding, but abolishes the accompanying adrenocortical and adrenomedullary activation.

Animals↗

PubMed1990

Plasma catecholamine, corticosterone and glucose responses to repeated stress in rats: effect of interstressor interval length.

Plasma noradrenaline (NA), adrenaline (A), corticosterone (CS) and glucose concentrations were determined in blood frequently sampled via a cardiac catheter from freely behaving rats exposed to five successive trials of water-immersion stress (WIS) with an interval between successive trials (interstressor interval; ISI) of either 24 hr or 72 hr. The first, acute exposure to WIS was accompanied by increased levels of plasma NA, A, CS and glucose which were substantially higher than those associated with handling or placement into a new cage. The magnitudes of the WIS-induced plasma NA, A, CS and glucose responses gradually declined across trials. However, five WIS exposures at a 24-hr ISI resulted in a faster and greater decrement of the plasma A, CS and glucose responses than five exposures at a 72-hr ISI. The data indicate that frequency of stressor presentation (i.e., length of interstressor interval) affects the adaptation pattern of neuroendocrine and metabolic responses to chronic intermittent stress. This finding supports the hypothesis that neuroendocrine adaptation to stress is (at least partly) similar to the process of behavioral or neurophysiological habituation to a sensory stimulus.

Animals↗