Jef L. Slangen

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.

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 animals behavioral coping style from an active to a passive form of avoidance responding, but abolishes the accompanying adrenocortical and adrenomedullary activation.

Release of endogenous catecholamines from rat hypothalamus in vivo related to feeding and other behaviors.

Abstract The release of endogenous noradrenaline (NA) and dopamine (DA) from various sites in the hypothalamus was determined in unanesthetized, freely moving rats by means of a push-pull perfusion technique in combination with a sensitive radiochemical assay. The perfusate was collected continuosly over 10-min periods for 4 to 8 hr. Patterns of feeding, drinking, grooming, and locomotor activity were recorded during the perfusion experiments. Release patterns and behavior recordings were analysed by tests of serial correlation. Although significant variations in catecholamine release over time were observed, they did not reflect a fixed autonomic periodicity. Release from the medial hypothalamus was measured in rats which had been deprived of food for 16 hr and were subsequently given free access to food. Before food presentation, mean NA release over 10-min periods was consistently higher than during satiety. Mean NA and DA release over 10-min periods before, during and after the occurence of feeding, drinking or grooming were calculated for the dorsomedial, perifornical, subfornical, and anterolateral hypothalamus of freely feeding rats. During feeding, NA (but not DA) release from the dorsomedial and perifornical areas was significantly elevated (40–50%) when compared with pre- or postfeeding values. An increase in catecholamine release was not observed during drinking or grooming. In addition, NA release from the anterolateral area correlated with locomotor activity. The enhancement of NA release from the perifornical area during feeding is considered to be specific as no change in release was observed even during the drinking vigorous response induced by angiotensin.

Plasma catecholamine and corticosterone responses to predictable and unpredictable noise stress in rats

Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) increases were determined in individual rats subjected to either 20 regularly or irregularly scheduled white-noise stimulations (4 min, 100 dBA). Blood was frequently sampled during the first and twentieth noise exposure, and during a reexposure after 24 hr. During the sampling periods, behavioral activities of the rats were recorded. The initial noise-induced CS release was partially reduced following the regular noise presentations. The increase after irregular presentations remained high. The difference in adrenocortical responsiveness between regular and irregular exposure persisted for 24 hr. The NA response to noise was partially attenuated following irregular administration of noise. However, regular exposure produced increased NA levels prior to noise presentation and a subsequent decrease during stimulation. After 24 hr, noise evoked an exaggerated initial NA release in the regular group. The noise-elicited rise in A was completely abolished after 20 noise presentations irrespective of whether these were applied regularly or irregularly. Reexposure after 24 hr evoked again a significant A response in both groups. No differences were observed in the habituation pattern of behavioral reactions among the regular and irregular groups. The results show that the sympathetic neural, adrenomedullary and adrenocortical systems differ in degree and speed of adaptation to intermittent stressful stimuli and in sensitivity to the predictability of stressors.

Predictive validity of the potentiated startle response as a behavioral model for anxiolytic drugs

The fear-potentiated startle (PSR) paradigm is a putative behavioral model for the determination of anxiolytic properties of drugs. The present study further investigated the predictive validity of the model. Predictive validity is high, when only drugs clinically used as anxiolytics attenuate PSR dose dependently. Results showed that startle potentiation decreased dose dependently after the administration of the anxiolytics CDP (2.5–10 mg/kg, IP) and alprazolam (1–3 mg/kg, IP). After administration of the clinically non-anxiolytic drugs amitriptyline (2.5–10 mg/kg, IP), carbamazepine (5–20 mg/kg, IP), fentanyl (0.0025–0.04 mg/kg, SC), naloxone (2.5–10 mg/kg, IP), nicotine (0.4–1.6 mg/kg, IP), alcohol (500–2000 mg/kg, IP), andd-amphetamine (0.6–2.4 mg/kg, IP), a dose-dependent decrease in startle potentiation was not found. The PSR correctly discriminated most of the drugs tested in clinically anxiolytic and clinically non-anxiolytic drugs. However, haloperidol behaved as a false positive, and results of nicotine and alcohol were at variance with results reported by others.

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.

Adaptation of plasma catecholamine and corticosterone responses to short-term repeated noise stress in rats

Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) concentrations were determined in blood frequently sampled via a cardiac catheter from freely moving rats exposed to three successive trials of white-noise stimulation (10 min, 100 dBA) with an intertrial interval of 30 min. During the sampling period, behavioral activities of the rats were recorded. It was demonstrated that the first exposure to noise induced a specific temporal pattern of neuroendocrine changes: Plasma A and NA contents increased rapidly and peaked early after stimulus onset but their peak-latencies were different (1 and 5 min, respectively). Noise offset was followed by quick return to basal levels. The changes in plasma CS concentrations were considerably slower in onset and slower in decline. The second and third exposure to this type of stressor resulted in attenuated hormonal responses and a reduced decrement of the NA/A-ratio, concurrent with a gradually less intense behavioral reaction. This differential pattern of plasma NA, A and CS responses following repetitive exposure to identical stressors, referred to as adaptation, is discussed with regard to the biochemical changes at various levels of the neuroendocrine systems involved.

Effects of training dose on discrimination and cross-generalization of chlordiazepoxide, pentobarbital and ethanol in the rat

Six groups of rats (N=8), trained to discriminate chlordiazepoxide (5 or 20 mg/kg), pentobarbital (5 or 15 mg/kg) or ethanol (750 or 1500 mg/kg) from saline in a two-lever food-reinforced procedure, were tested for stimulus generalization with the three drugs. Training drug, but not training dose, affected the extent of generalization to a test drug; symmetrical generalization between chlordiazepoxide and pentobarbital and asymmetrical generalization between chlordiazepoxide and ethanol and between pentobarbital and ethanol was observed. Training dose level affected (1) slope and ED50 of the generalization gradients of training drugs and substitution drugs, (2) discriminative performance, (3) response bias and (4) threshold dose for response suppression. Indices of lever selection and percentage drug-appropriate lever responses yielded similar generalization maxima, slopes and ED50s. The potency of chlordiazepoxide relative to the potency of pentobarbital to induce drug stimulus generalization varied across the experimental groups. The results indicate differences between the discriminative effects of chlordiazepoxide, pentobarbital and ethanol. It is suggested that the discriminative effects of chlordiazepoxide, pentobarbital and ethanol are not based on their response rate modulating effects and that training dose is not a determinant for the extent of cross-generalization between these compounds.

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 rats individual behavioral strategy.

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 (socalled “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.