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Biomedical subjects

G Croiset

Publications and source records attributed to G Croiset.

At least 37 records · Page 2Linked to original sources

ACTH: a structure-activity study on pilocarpine-induced epilepsy.

Intracerebroventricularly applied pilocarpine (2.4 mg/2 microliters) immediately produced symptoms of epilepsy, ranging from akinesia to motor seizures, in rats. Whereas ACTH-(1-39), ACTH-(1-24), ACTH-(1-18), ACTH-(1-16) and ACTH-(18-39) were not active, subcutaneous pretreatment with smaller ACTH-like fragments, such as ACTH-(4-9), ACTH-(4-10), ACTH-(4-10)(7D-Phe), ACTH-(7-16), and Org2766, reduced the severity of the epilepsy. Moreover, fewer rats developed motor seizures. Thus, ACTH fragments devoid of peripheral endocrine activity reduce pilocarpine-induced epileptiform activity in rats. A narrow bell-shaped dose-response relationship was found. Except for ACTH-(7-16), which was active in a dose of 1 and 10 micrograms/rat s.c., the other fragments were only active at one dose (10 micrograms/rat). The anti-epileptic properties appeared to reside in the sequence 1-16, and more specifically in the sequences 4-7 and 7-16, of the ACTH molecule.

Adrenocorticotropic Hormone↗

Shock-prod burying test in rats: autonomic and behavioral responses.

Heart rate (HR), core temperature (CT) and gross locomotor activity (GLA) were recorded in rats by a computerized telemetry system before, during and after 15-min exposure to a constantly electrified (2mA) or nonelectrified (0mA) prod which was presented through a hole in the home cage with woodshavings on the floor [shock-prod burying (SPB) test]. Measurement of both autonomic and behavioral response continued up to 60 min after introduction of the prod in the home cage. Twenty-four h after the SPB test, rats were tested for retention. During the SPB test, significant increases in HR, respective to baseline values, were observed in both the 2mA and 0mA group, but the tachycardiac response in the former group significantly outweighed that in the latter group. In shocked rats, HR remained elevated during the entire 45-min posttest period, whereas HR declined immediately after removal of the prod in nonshocked animals. An onset in rise in CT was observed in the 2mA, but not in the 0mA group, during prod exposure time, which eventually resulted in an additional-more than two-fold--increase after termination of the test and outlasted total recording time. Marked behavioral activation was observed in the 2mA group, whereas the 0mA responded to a lesser extent. Approach and exploration of the prod was reduced when the prod was electrified. The total time spent by rats burying the prod was significantly longer in the shocked than in the nonshocked group. When exposed to the nonelectrified prod after 24 h, total burying time was reduced in the 2mA group but still significantly longer than in the 0mA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A role for the autonomic nervous system in modulating the immune response during mild emotional stimuli.

The role of the autonomic nervous system in the modulation of the immune response to emotional stimuli, was established in rats subjected to the passive avoidance test. An increase in splenic primary antibody response directed against SRBC was found after exposure of rats to the passive avoidance apparatus (novelty). Both local surgical denervation of the spleen and beta-receptor blockade (timolol, 1 mg/kg i.p. 1 h prior to testing) prevented the increase in primary antibody response.

Animals↗

Passive avoidance behavior, vasopressin and the immune system. A link between avoidance latency and immune response.

The relation between passive avoidance behavior and primary antibody response was studied in rats. The avoidance latency was varied by means of variation of the shock intensity during the learning trial; a higher shock intensity resulted in a longer avoidance latency at the retention test. The avoidance latencies were inversely proportional to the magnitude of the primary antibody response. Neuropeptides, such as [Arg8]-vasopressin (AVP) were shown to potentiate retrieval processes. Administration of 10 ng desglycinamide AVP (DGAVP) 1 h prior to the retention test facilitated passive avoidance behavior (increase in avoidance latency). Conversely i.c.v administration of vasopressin antiserum resulted in attenuation of the avoidance behavior. The effects of altered passive avoidance behavior as a consequence of i.c.v. administration of DGAVP or vasopressin antiserum were studied on the primary antibody response. Again an inversely proportional relationship between the avoidance latency and the magnitude of the primary antibody response was observed. The results show that the immune system can specifically react to graded environmental stimuli. It is hypothesized that vasopressin may be an endogenous mediator determining the outcome of the avoidance behavior and the primary antibody response.

Animals↗

Induction of beta-endorphin secretion by lymphocytes after subcutaneous administration of corticotropin-releasing factor.

Cells of the immune system can be stimulated to secrete POMC-derived peptides such as beta-endorphin and ACTH. Recently, it has been reported that CRF induces beta-endorphin secretion by human peripheral blood mononuclear cells in vitro (1). It has been shown that interleukin-1 (IL-1) mediates the CRF-induced secretion of beta-endorphin by lymphocytes in vitro. In the present report it is demonstrated that sc administration of CRF to rats can also induced beta-endorphin secretion by lymphocytes from spleen and mesenteric lymph nodes. Moreover, this CRF-induced secretion of beta-endorphin coincides with enhanced secretion of IL-1 by macrophages. Previously, we reported that IL-1 can activate CRF neurons in the hypothalamus of the brain. Our data indicate the existence of an intricate relationship between CRF and IL-1, peptides that can be viewed as playing a pivotal role in the interaction between the central nervous system and the immune system.

Animals↗

Effects of environmental stimuli on immunoreactivity: further studies on passive avoidance behavior.

Rats were immunized against sheep red blood cells (SRBC) immediately after the passive avoidance test; 5 days later the antibody response was measured by determining the number of splenic antibody-secreting B cells. Subjection of rats to habituation trials in the passive avoidance apparatus (apparatus control group) resulted in an enhanced number of antibody secreting cells compared to rats that remained in their home cage. The same phenomenon was observed in rats that were immunized immediately after the learning trial (electric footshock). In animals that showed passive avoidance behavior when tested for retention 24 h after the learning trial, the initially enhanced immune response was down-regulated to the level of rats that remained in their home cage or even lower. The above-mentioned alteration in number of anti-SRBC antibody-secreting cells was only observed in rats that were immunized 15 min after the retention test. In rats that were immunized 1, 4, or 8 h after the retention test no alteration in primary antibody response was observed. In rats of the apparatus control group that were immunized immediately after the retention test an elevated primary antibody response was observed 4, 5, 6, and 7 days after immunization; thus, the changes in immune response were not the consequence of a delayed or accelerated induction of the anti-SRBC response. No change in the absolute number of leukocytes in peripheral blood was observed in the different experimental groups. Moreover, the observed differences in response were not caused by a shift in the percentage of total T, B, Th, or Ts/c cells. The alteration in primary antibody response was only observed in the spleen. The antibody titer in trunk blood did not differ among the different groups and no significant change in number of antibody-secreting cells in the parathymic lymph node was observed. These results show that rats can specifically register different environmental stimuli and as a consequence of that perception there is a change in antibody-secreting cells in the spleen.

Animals↗

Modulation of the immune response by emotional stress.

The influence of mild, emotional stress was investigated for its effect on the immune system by subjecting rats to the one-trial-learning passive avoidance test. The reactivity of the immune system was tested by determining the proliferative response after mitogenic stimulation in vitro as well as the capacity to generate a primary antibody response in vivo after immunization with sheep red blood cells. Our results demonstrate that exposure of rats to a single electric footshock (learning trial) or habituation to the passive avoidance apparatus, induces an increase of the immune response in vitro and in vivo. Thus, emotional stimuli seem to facilitate immunological responsiveness. However, when the animal is confronted with a conflict situation, as tested by the retention of the avoidance response after a single learning trial, the initially enhanced reactivity of the immune system decreases. It is concluded that the immune system is capable of reacting specifically and immediately to distinct psychological stimuli.

Animals↗

Modulation of the immune response by POMC-derived peptides. I. Influence on proliferation of human lymphocytes.

The POMC-derived peptides beta-endorphin and ACTH are capable of modulating an immune response in physiological concentrations. These neuropeptides can either enhance or inhibit the proliferative response of human peripheral blood lymphocytes after stimulation with the mitogen concanavalin A. The modulatory action of the peptides is not only dependent on the concentration but appears to be donor dependent. The response pattern observed is not determined by a selective affinity for certain amino acid sites on the molecules with "enhancing" or "inhibiting" activities, since fragments of beta-endorphin and ACTH also produce a differential donor-dependent response pattern.

Adrenocorticotropic Hormone↗

Differential effects of DGAVP on acquisition and extinction of active avoidance behavior.

DGAVP facilitates consolidation and retrieval of active and passive avoidance behavior. In this study it was tested whether the long-term behavioral effects of DGAVP are the consequence of an initial increase in behavioral arousal during the learning phase. Animals that were preestimated in an open field test to be low active showed a lower number of conditioned avoidance responses (CAR's) during acquisition and extinction of a shuttle-box task than high active rats. DGAVP was administered 40 min prior to the 1st acquisition session. The immediate effect of DGAVP was a shift in the bell-shaped curve of the relation between arousal and performance (13); an increase in acquisition performance was observed with a low dose of DGAVP (0.1 microgram), while a decrease was found with a high dose of DGAVP (1 microgram). A dose-dependent inhibition of extinction was found in both low and high active animals. These results suggest an immediate effect of DGAVP on the rate of acquisition behavior, which may be a direct consequence of its arousing properties, and a long-term effect on extinction, indicating the formation of memory traces specific for vasopressin-related neuropeptides.

Animals↗

The effect of corticotropin-releasing factor (CRF) on autonomic and behavioral responses during shock-prod burying test in rats.

When administered intracerebroventricularly (ICV) in rats, corticotropin-releasing factor (CRF) possesses arousing and anxiogenic properties, which may be found reflected in autonomic and behavioral activation. As these responses are dependent on dose and situation, ICV-injected CRF may affect behavioral responses to a defined stimulus in a different fashion than autonomic concomitants. Two experiments were conducted in order to test this hypothesis. In both experiments, rats were treated ICV with CRF or an artificial cerebrospinal fluid (aCSF) 5 min prior to a 15-min exposure to an electrified prod (shock-prod burying test, SPB test) in their home cages. In the first experiment, 0.3 ng CRF injected ICV in unhandled rats significantly reduced the prod-burying response to electric shock, in favor of immobility, whereas following 300 ng CRF ICV, the predominant behavioral response was grooming behavior. In contrast, habituated rats, implanted with telemetric devices to measure heart rate, core temperature, and gross activity in the second experiment, showed a significant increase of burying behavior after 0.3 ng CRF ICV, in comparison to vehicle-treated controls. However, simultaneous cardiac acceleration was of the same magnitude and duration in both groups. In addition, whereas similar rises in CT were observed in both groups during the SPB test, CRF-treated rats showed more marked rise in core temperature during the first 15 min of the posttest period. At the 24-h retention test, rats belonging to the CRF group showed burying behavior and HR responses, in onset, magnitude, and duration similar to day 1, whereas extinction of the burying response and tachycardia was found in controls. Changes in CT, although less marked, showed the same pattern as on day 1 in both groups. These results show a differential effect of central CRF on behavioral and autonomic activation induced by a well-defined stressful stimulus. The response to CRF seems to be not only situation related, but also dependent on the pretest experience of the animal.

Animals↗