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J L Slangen

Publications and source records attributed to J L Slangen.

At least 73 records · Page 4Linked to original sources

Effects of chlordiazepoxide training dose on the mixed agonist-antagonist properties of benzodiazepine receptor antagonist Ro 15-1788, in a drug discrimination procedure.

In experiment 1, rats (n = 12) were trained to discriminate the benzodiazepine (BDZ) compound chlordiazepoxide (CDP, 20 mg/kg, IP) from saline in a two-lever food-reinforced procedure, and subsequently were tested for stimulus control with different doses of CDP, Ro 15-1788 (a proposed BDZ receptor antagonist) and Ro 15-1788 plus 20 mg/kg CDP. Ro 15-1788 (0.63-40 mg/kg) dose-dependently antagonized CDP, and induced predominantly saline appropriate responding when administered alone. Thereafter, the same rats were retrained by progressively decreasing the training dose, to discriminate 2.5 mg/kg CDP from saline, and were tested again with the same compounds. Ro 15-1788 (0.16-40 mg/kg) now failed to antagonize CDP (2.5 mg/kg) and increased the percentage of drug-appropriate responding in a dose-related manner when administered alone. In experiment 2, separate groups of rats (n = 10) were similarly trained to discriminate either 15 or 3 mg/kg CDP from saline. Tests with CDP, Ro 15-1788 and Ro 15-1788 plus CDP (either 15 or 3 mg/kg) yielded similar results to experiment 1, suggesting that the training dose effects on generalization and antagonism of Ro 15-1788 were not affected by the manner in which the lower CDP dose acquired drug stimulus control. It is concluded that mixed agonist-antagonist properties are apparent after variations of the BDZ training dose in a drug discrimination procedure.

Animals↗

Differential interactions between chlordiazepoxide, pentobarbital and benzodiazepine antagonists Ro 15-1788 and CGS 8216 in a drug discrimination procedure.

Rats were trained to discriminate either chlordiazepoxide (CDP, 4 mg/kg, IP, N = 8) or pentobarbital (PB, 10 mg/kg, IP, N = 8) from saline in a two-lever food-reinforced procedure. CDP and PB dose-dependently substituted for each other (greater than or equal to 90% drug lever responses); indicating that their discriminative stimulus properties were closely similar. However, discriminative stimulus control induced by CDP and PB differentially was affected by the proposed benzodiazepine (BDZ) antagonists Ro 15-1788 (0.08-20 mg/kg, IP) and CGS 8216 (2.5-20 mg/kg, IP) in each experimental group; suggesting that the discriminative stimulus properties of CDP and PB are mediated by different mechanisms of action. When administered alone, Ro 15-1788 (5 and 20 mg/kg), but not CGS 8216, induced CDP like discriminative effects, suggesting that Ro 15-1788 may have partial (BDZ like) agonist properties, not shown by CGS 8216. Additional evidence for a behavioral difference between Ro 15-1788 and CGS 8216 is suggested by differential effects of both compounds on response rate. The results may reflect differential interactions of the compounds with the BDZ receptor-GABA receptor-Cl- ionophore complex.

Animals↗

Short-term feeding-related changes in mediodorsal hypothalamic catecholamine release.

Release of noradrenaline (NA), adrenaline (A) and dopamine (DA) was measured in vivo per minute before and after food presentation in satiated rats that had a cannula in the mediodorsal hypothalamic area (MDH). Release of NA was significantly increased above baseline during a period of a few minutes in which feeding took place. In the period following feeding there were peaks in the release of both NA and A. In DA release no changes were observed. Since a statistical correlation between release of NA or A and locomotor activity was not found, it is suggested that the increased release of NA and A is specifically related to food-motivated behavior.

Animals↗

Habituation of early and late visual ERP components and the orienting reaction: the effect of stimulus information.

Single trial event-related potentials at Fz, Cz, Pz and Oz were measured concurrently with pupil reactions and skin conductance reactions in a habituation paradigm. One group of subjects (n = 16) was given 36 simple visual stimuli and a second group (n = 16) 36 complex visual stimuli of equal duration, brightness and dimensions. No task-relevance was given to the stimuli. Under these circumstances we found rapid habituation (within 6 trials) of the vertex N1. Because we used long, variable interstimulus intervals, the N1 decrease could not be explained by refractory effects. Habituation rates of N1 and the concurrently measured SCR did not differ. Although the P3 showed significant habituation over the 12 trials (except at Oz), it habituated slower than the N1 and the SCR. The complex stimulus condition elicited larger P3b waves. No effect of stimulus complexity was found on the N1 and the SCR. The relevance of these results for the OR is discussed.

Adult↗

The effects of uncertainty and task-relevance on habituation and recovery of the electrodermal and visual orienting reaction.

Habituation and recovery of the skin conductance reaction (SCR) and visual orienting reaction (VOR) were investigated. Half the subjects (total N = 48) were instructed to memorize a complex visual stimulus (TR), while the other half received a non task-relevant instruction (NTR). All subjects were exposed to two series of 16 identical stimuli. At trial 17 the location of the stimulus changed. Half the subjects in both groups received a priori information about the stimuli, the other half did not. Task-relevance led to slower SCR habituation and longer VORs. In the TR condition the VOR latency time rapidly decreased, indicating the development of a set. In terms of SCR frequency, but not in terms of SCR magnitude OR recovery was stronger in the task-relevant condition. However, all subjects oriented visually to the stimulus change. No habituation of the VOR was found using a drift-free technique for measuring eye-movements. It is concluded that the SCR and the VOR latency data supply evidence for a structural difference between task-relevant and task-irrelevant ORs.

Adult↗

Subjective, clinical and EMG effects of biofeedback and splint treatment.

Patients suffering from myofascial pain dysfunction (MPD) were trained to maintain constant levels of EMG masseter activity with the aid of biofeedback. Treatment effects were compared with the effects of a nightly full-coverage splint and with a no-treatment control group. The biofeedback group showed significantly more improvement in clinical dysfunction and subjective symptoms related to pain and mandibular movement than either the splint group or the control group. The results of the splint group were not substantially different from the control group. The EMG results indicate that during biofeedback the ratio between EMG activity of the trained and the non-trained masseter shifted towards a higher contribution of the trained muscle. This effect was significant at high task levels. During biofeedback EMG task performance improved but this effect did not generalize to non-feedback situations. It is suggested that the treatment effects of biofeedback depend upon the increase in perceived control reported by the biofeedback group.

Biofeedback, Psychology↗

Diazepam-induced changes in signal detection performance. A comparison with the effects on the Critical Flicker-Fusion Frequency and the Digit Symbol Substitution Test.

The effects of 10 mg diazepam on signal detection theory measures (stimulus sensitivity, response bias) and reaction times were studied in a 1-hour visual signal detection task with high and low signal probability, and on performance in two short-duration tasks: Critical Flicker-Fusion Frequency (CFF) and the Digit Symbol Substitution Test (DSST). 12 healthy volunteers participated in this placebo-controlled, double-blind cross-over study. Diazepam affected the stimulus sensitivity and the reaction times of hits in the signal detection task. DSST performance was also impaired while CFF did not change after diazepam treatment. No relationship between serum diazepam concentration and change in task performance was found. It is concluded that diazepam affects signal detection performance, independent of signal probability. A short-duration task like the DSST is as sensitive to the effects of diazepam as the (long-duration) signal detection task.

Adolescent↗

The Ro 15-1788 cue: evidence for benzodiazepine agonist and inverse agonist properties.

Rats discriminating Ro 15-1788 (10 mg/kg, i.p.) from vehicle completely generalized this cue to typical benzodiazepines, and partially generalized it to barbiturates, pentylenetetrazol, CGS 8216, beta-CCM and PK 8165. CL 218872, Ro 5-4864, phenytoine, progabide, propranolol, yohimbine and various CNS stimulants predominantly induced vehicle-appropriate responding. Chlordiazepoxide, pentobarbital, CL 218 872, PK 8165, pentylenetetrazol, CGS 8216 and beta-CCM failed to block the Ro 15-1788 cue. Generalization to both anxiolytics/anticonvulsants and anxiogenics/(pro) convulsants suggests that Ro 15-1788 has benzodiazepine agonist and inverse agonist properties.

Animals↗

Stimulus control induced by benzodiazepine antagonist Ro 15-1788 in the rat.

The imidazodiazepine Ro 15-1788 is a proposed benzodiazepine receptor antagonist. Recently however, behavioural effects of Ro 15-1788 have been demonstrated. In the present study, rats (n = 12) were trained to discriminate Ro 15-1788 (10 mg/kg, IP, t = 15 min) from vehicle in a two-lever food-reinforced procedure. All rats showed a reliable discrimination (mean injection-appropriate lever responding greater than 85%) after about 60 daily training sessions. Drug stimulus control was evidenced by an orderly generalization gradient obtained with 0.01-30 mg/kg Ro 15-1788 (ED50 for stimulus generalization: 0.12 mg/kg). Since even low doses of Ro 15-1788 have discriminative effects in the rat, it is concluded that Ro 15-1788 may have potent behavioural activity.

Animals↗

Myofascial pain-dysfunction: subjective signs and symptoms.

Dental patients were classified by experienced dentists as MPD or non-MPD patients. Apart from the symptoms often used as criteria for such a classification, there is a broad range of symptoms and patient characteristics associated with MPD. Because of procedural and methodologic problems, little is known about the strength of these associations. Because reliable knowledge about symptoms and characteristics of MPD is needed for MPD etiology and for adequate treatment evaluation, the present study tried to establish which subjective signs and symptoms differentiate MPD from non-MPD patients. Results of a questionnaire show that 10 items classified 86% of the patients correctly. Among them, restricted mouth opening and sounds at jaw movement had the highest discriminative power. Pain in the jaw area also showed a highly significant difference between the patient groups. When patient selection is based on these criteria, approximately the same patient groups are obtained by a time-consuming dental examination and by a low-cost questionnaire. Results also showed that reported oral habits such as chewing on hard or tough objects and lip-tongue-cheek biting do not differentiate the two groups. Symptoms related to ears and eyes discriminate the groups only marginally. Sleep-related symptoms, with awakening with stiff or painful jaws as the most important item, differentiate patients in a more substantial way. The suggestion from a great number of studies that stress and tension are etiologic factors in MPD is not supported by the present results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The electrocardiogram during emotional and physical stress.

The electrocardiographic response pattern during exercise at low and high heart rate was compared with the response pattern during emotional stress. Qualitative differences between exercise and emotional stress were obtained, i.e. during exercise the ST segment was more depressed, T-wave amplitudes were larger and QT and PQ were significantly shorter than during emotional stress. The results do not support the suggestion that emotional stress evokes an exercise-like cardiovascular response pattern, which may lead to a metabolically maladaptive situation. The results are in accordance with the hypothesis that the ECG changes during emotional stress are similar to the ECG changes during right stellate stimulation, while the ECG changes during exercise are similar to the ECG changes obtained during left stellate stimulation.

Adolescent↗

Alcohol effects on signal detection performance.

The acute effects of alcohol (0.7 g/kg) on visual signal detection performance and critical flicker fusion frequency (CFF) of normal volunteers were investigated using a signal detection theory analysis. When signal probability was low, alcohol affected the stimulus sensitivity and the reaction times of hits. Under a high signal probability these indices were not affected, whereas the response bias did not change after the administration of alcohol under both signal probabilities. CFF values were not altered by alcohol. A correlation was found between the magnitude of the alcohol effect and the performance level under placebo. Changing the signal probability caused significant differences between the sensitivity measures, the response bias measures and the reaction times of hits. It is concluded that alcohol affects signal detection performance under conditions of low signal probability. Individuals with a relatively low performance level are more susceptible to the effects of alcohol.

Adult↗

External stimulus control in a "drug-discrimination" procedure: drug effects and inter-animal variation.

Rats (N = 12) were trained to discriminate between two stimulus conditions S1 and S2, consisting of combinations of visual and tactile stimuli [S1: box lighted (L) and wooden floor insert present (W); S2: box dark (D) and grid floor present (G)] in a two-lever discrimination procedure. S1 was continuously present during half of the sessions, and S2 was continuously present during the remaining sessions. Morphine (0.3--6 mg/kg) and haloperidol (0.04--0.08 mg/kg), but not chlorpromazine (1--4 mg/kg) and scopolamine (0.031--0.125 mg/kg), decreased the accuracy of discriminative responding during S1 sessions. None of the drugs significantly affected discrimination accuracy during S2 sessions. After drug testing was completed, reversed combinations of the visual and tactile stimuli were tested (i.e. L + G, and D + W). Inter-animal variation in the control by the component stimuli was observed. The results suggest that "intermediate results" (i.e. equal responding on drug and saline lever) in drug discrimination research, if observed at the highest dose of a drug at which animals still respond, may be interpreted in terms of a drug-induced disruption of discriminative responding. The results further suggest that inter-animal variation in the outcome of drug generalization tests may be partly related to inter-animal variation in the degree of stimulus control by different components of the training drug stimulus.

Animals↗

Effects of d-amphetamine and morphine on delayed discrimination: signal detection analysis and assessment of response repetition in the performance deficits.

Signal detection analysis was used to examine the effects of d-amphetamine and of morphine on delayed visual discrimination (delay intervals: 0-4-8-16 s) in male rats. The probability of response repetition in the discrete trial two-choice discrimination procedure was used as an additional behavioral measure. d-Amphetamine (0.16-0.33 mg/kg) decreased SI ( a measure of the animals' sensitivity to the discriminative stimuli) at delays between stimulus presentation and opportunity for responding of 4-16 s, and did not affect SI at the 0 s delay. Morphine (1-3 mg/kg) decreased SI at all delay conditions. d-Amphetamine, but not morphine, affected RI (a measure of the animals' bias towards responding on one lever or the other) and increased the probability of response repetition. The bias measure B inches was affected neither by d-amphetamine nor by morphine. It is concluded that d-amphetamine, but not morphine, produces a deterioration of delayed discrimination performance, probably as a result of drug-induced response perseveration. It is suggested that, under the conditions of the present study, the selective deterioration of discrimination performance after d-amphetamine at delays which are longer than 0 s may not be primarily related to a drug-induced disruption of a short-term memory mechanism, but may be related to drug effects on response output.

Animals↗

Effects of drug-induced differences in reinforcement frequency on discriminative stimulus properties of fentanyl.

Rats were trained to discriminate between fentanyl (0.04 mg/kg) and saline in a two-lever procedure. Using a FR 10 schedule of food reinforcement, drug-induced differences between the number of reinforcers obtained under fentanyl and saline conditions were observed. The effect of eliminating these differences on the outcome of generalization tests was investigated by different manipulations. In one group (N = 10), the FR 10 schedule used during saline sessions was changed to FR 6 during drug sessions. In a second group (N = 12), saline sessions ended after the number of reinforcers obtained was equal to the number obtained during the preceding drug session. A control group (N = 10) was trained using a FR 10 schedule under both conditions. Elimination of differences in reinforcement frequency accelerated the acquisition of the discrimination, diminished response bias, flattened the slope and reduced the ED50 value of generalization gradients of fentanyl, morphine and sufentanil and increased the ED50 value of naloxone in antagonizing 0.04 mg/kg fentanyl. It is concluded that the unconditioned effects of 0.04 mg/kg fentanyl on response rate in a FR 10 procedure lead to differences between saline and drug sessions which contribute to the apparent discriminative stimulus properties of fentanyl.

Animals↗

Acute effects of naloxone and naltrexone, but lack of delayed effects, on exploratory behavior in the rat.

Exploratory head-poke responses, locomotor activity, and rearing were studied in five groups of rats (n = 8 per group) during two 30-min sessions. The opiate antagonists naloxone and naltrexone (0.5 and 2 mg/kg) were administered once, 30 min before the first session. Delayed drug effects were studied during the second session, 24 h after the first session. During the initial 10 min of the first session naloxone and naltrexone decreased the number of head-poke responses without reducing locomotor activity and rearing. Both drugs decreased the number of head-poke responses, locomotor activity, and rearing during the remainder of this session. Equivalent doses of naloxone and naltrexone produced similar effects. The duration of a head-poke response increased during the session. Drug effects on head-poke duration were not observed. Delayed drug effects on behavior during the second session were not obtained. The observation that both naloxone and naltrexone were effective in the present procedure suggests that the effects of naloxone and naltrexone reported here are a function of opiate antagonist properties of these drugs. The data suggest further that the extent to which opiate receptor blockade results in a specific reduction of exploratory behavior may be partly dependent upon the length of the test session.

Animals↗

Eye-movements in a two-dimensional plane: a method for calibration and analysis using the vertical and horizontal EOG.

A method for calibration, orthogonalization and standardization of eye movements is described. The method is based on linear transformation of the horizontal and vertical EOG. With this method it is possible to measure the locus of eye fixation on a TV screen and its associated fixation time. Because of the used time constant (TC) of 36 sec, subjects must look at the centre of the TV screen or at random places on the screen during the interstimulus intervals (ISIs). For the EOG registration pre-amplifiers with a long TC were used to cut off slow changes in polarization caused by the electrode-electrolyte combination. In the calibration procedure only four orthogonal stimulus points were used. In an experiment to evaluate this method, subjects had to fixate letters on a TV screen in 12 different pre-determined positions. The distance between the measured locus of fixation and the coordinates of the stimulus was measured. The mean horizontal errors ranged from 1.4-2.2 degrees of arc and the mean vertical errors from 2.4-3.8 degrees of arc across subjects. It was concluded that accuracy was within acceptable limits, despite the fact that eye movement behaviour during the ISI was free. It was shown that the method is insensitive to non-orthogonality of the vertical and horizontal EOG. Calibration and transformation can be done by any real time computer system. The method is suitable for measuring, e.g. the visual orienting reaction (VOR), and it can also be applied in event related potential (ERP) studies where ocular fixation is used.

Adult↗