J. van der Gugten

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.

Daily variations in plasma noradrenaline, adrenaline and corticosterone concentrations in rats ☆

Plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) concentrations were determined in blood samples taken once every hour during a 12-hr light/12-hr dark period from freely moving rats with a permanent heart cannula. Before, during and shortly after each blood sampling, behavioral activity was recorded. All rats exhibited a very pronounced peak in CS concentrations at the end of the light period, indicating normal circadian rhythmicity. Plasma NA and A contents varied significantly over the 24-hr sampling period. During nighttime, the behaviorally active phase, mean levels of circulating A and NA were significantly higher than during daytime resting period. Significant correlations between the daily NA, A and behavioral activity patterns were found only when uncorrected data were considered. In contrast, no significant correlations were found for values corrected for circadian trends, indicating that circadian patterns of NA, A and behavioral activity rather than their short-term fluctuations are similar. It is concluded that the circadian variations in plasma NA and A reflect a common activation of both the neural and adrenomedullary parts of the sympathetic autonomic nervous system, most likely associated with the daily patterning of behavior activities. On short-term basis through the day however, a dissociation between these two parts can occur suggesting separate regulating mechanisms for the fine tuning of physiological processes.

Effects of methylphenidate, desipramine, and l-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder

The objective of this study was to investigate the effects of methylphenidate (MPH) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder (ADHD) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were. In addition to MPH, two other drugs were administered in order to affect both transmitter systems more selectively, L-dopa (dopamine (DA) agonist) and desipramine (DMI) (noradrenaline (NA) re-uptake inhibitor). Sixteen children with ADHD performed a stop-task, a laboratory task that measures the ability to inhibit an ongoing action, in a double-blind randomized within-subjects design. Each child received an acute clinical dose of MPH, DMI, L-dopa, and placebo; measures of performance and plasma were determined. The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa. The response-time to the stop-signal was marginally shortened after intake of DMI. MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone. No effects of L-dopa whatsoever were noted. Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo. It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms. The improved inhibition under DMI could be serotonergically mediated.

Regional concentrations of noradrenaline and dopamine in the frontal cortex of the rat: dopaminergic innervation of the prefrontal subareas and lateralization of prefrontal dopamine

Catecholamine levels in the two subareas of the prefrontal cortex and in one non-prefrontal region of the rat frontal lobe were measured radioenzymatically. In contrast with noradrenaline (NA), the distribution of dopamine (DA) in the frontal lobe is markedly heterogeneous. DA levels of the orbitofrontal and medial prefrontal subarea are, respectively, 3 and 4 times higher than those of a non-prefrontal region of the frontal lobe, confirming the expectation of neuroanatomical findings. Furthermore, it appears that at the population level, DA levels of the medial prefrontal subarea are lateralized, the left hemisphere being significantly higher than the right hemisphere.

Influence of the mesocortical dopaminergic system on activity, food hoarding, social-agonistic behavior, and spatial delayed alternation in male rats.

In order to assess the behavioral role of the dopaminergic mesocortical input to the prefrontal cortex, bilateral lesions were made in the ventral tegmental area (VTA). The possibility of a functional recovery by the administration of a dopamine agonist was examined. General activity, food hoarding, social-agonistic behavior, and spatial delayed alternation performance were recorded in rats with VTA lesions and in sham-operated animals. In the open field animals with VTA lesions were more active but showed less anxiety. Food hoarding was impaired. In dyadic interactions with sham-operated opponents, VTA rats were socially more active, whereas sham operates performed more keeping down and aggressive grooming. This behavioral deficit was partially recovered when apomorphine was administered prior to testing. VTA animals were impaired in the performance of a spatial delayed alternation task with an intertrial interval of 15 s, whereas no impairment was found with a 0-s intertrial interval. The theoretical implications of these findings are discussed.

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.

Mouse strain differences in autonomic responses to stress

In humans, anxiety disorders are often accompanied by an overactive autonomic nervous system, reflected in increased body temperature (BT) and heart rate (HR). In rodents, comparable effects are found after exposure to stress. These autonomic parameters can give important information on stress and anxiety responses in mice. In the present experiments, stress reactivity of three frequently used mouse strains [129 Sv/Ev, Swiss Webster (SW) and C57 BL/6] was assessed using their autonomic stress responses. BT, HR and activity were telemetrically measured. Undisturbed circadian rhythms already showed clear differences between the mouse strains. Hereafter, autonomic responses to stressors with increasing intensity were measured. Strain differences were found in magnitude and duration of the stress responses, especially after high‐intensity stressors. Generally, C57BL/6 mice showed the largest autonomic response, SW the lowest and the 129Sv/Ev the intermediate response. Interestingly, the observed ranking in autonomic stress response does not match the behavioral stress responsivity of these strains. Finally, sensitivity to the anxiolytic diazepam (0, 1, 2, 4 and 8 mg/kg) was tested using the stress‐induced hyperthermia paradigm. Pharmacological sensitivity to diazepam differed between the strains with the 129Sv/Ev being most sensitive. These studies show that simultaneous measurement of behavioral and autonomic parameters under stressful conditions contributes considerably to a better interpretation of anxiety and stress levels in mice.

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.

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.