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D de Wied

Publications and source records attributed to D de Wied.

At least 19 recordsLinked to original sources
PubMed1992

Differential effects of ACTH4-10, DG-AVP, and DG-OXT on heart rate and passive avoidance behavior in rats.

A computerized telemetry system was used to monitor heart rate (HR), core temperature (CT), and gross locomotor activity in rats treated with saline or neuropeptides during a passive avoidance behavior task. Rats were exposed to a single mild footshock (0.15 mA, for 3 s). Retention tests were conducted at 24 and 48 h after the learning trial. One h prior to the 24-h retention test, each rat received one of the following treatments (SC): saline (SAL), desglycinamide [Arg8]-vasopressin (DG-AVP), ACTH4-10, or desglycinamide-oxytocin (DG-OXT), at a dose of 3 micrograms/rat for DG-AVP and DG-OXT, and 50 micrograms/rat for ACTH4-10. Rats treated with SAL showed a modest increase in avoidance latency accompanied by bradycardia at both retention tests. Rats receiving DG-AVP retained the highest avoidance latency among the experimental groups at both the 24- and 48-h retention test. These rats showed a decrease in HR of the same magnitude as the SAL-treated animals at both retention tests. Rats treated with ACTH4-10 showed an increase in avoidance latency during the 24-h but not during the 48-h retention test. In addition, following ACTH4-10 treatment, a tachycardiac response was found during the 24-h retention test. DG-OXT induced both behavioral and cardiac responses opposite to those found in rats given DG-AVP. CT gradually increased while the rats remained on the platform, irrespective of the treatment. Changes in HR and CT were not influenced by somatomotor activity, as no difference in gross locomotor activity was found among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Corticotropin-releasing factor induces differential behavioral and cardiovascular effects after intracerebroventricular and lateral hypothalamic/perifornical injections in rats.

The contribution of the lateral hypothalamic/perifornical (LH/PFx) area in mediating central effects of corticotropin-releasing factor (CRF) on cardiovascular and behavioral activity was assessed by monitoring blood pressure, heart rate and behavioral responses for a 45-min period after injections of various doses of CRF into the LH/PFx region or the lateral cerebral ventricle (intracerebroventricular, i.c.v.) in conscious, unrestrained rats in a familiar environment. After LH/PFx injection, CRF (3 and 30 ng) dose-dependently induced behavioral activation, predominantly consisting of grooming, eating and locomotor activity. Concomitantly, dose-related increases in mean arterial pressure (delta MAP) and heart rate (delta HR) were observed. Increases in MAP and HR following injection of 3 ng CRF were associated with the paroxysmal occurrence of behavioral activation and as such superimposed on CRF-induced elevation of baseline MAP and HR. Thirty nanograms CRF given i.c.v. produced grooming behavior similar to that observed after the same dose injected into the LH/PFx region, but failed to induce significant changes in cardiovascular concomitants. Rats receiving 100 ng CRF i.c.v., showed a significant increase in behavioral activity, respective to rats treated with 30 ng CRF in the LH/PFx, the tachycardiac responses, however, being similar in these groups. Both doses of CRF i.c.v. failed to induce significant delta MAP. The effects of CRF on cardiovascular and behavioral activity were more marked when the peptide was injected into the caudal part of the LH than those measured after administration into the rostral LH. Similarly, injections of CRF around or dorsal to the fornix (PFx) were more effective than those located ventrally to it. This site specificity of CRF-evoked responses was reflected in differential time response relations of the various effects. In summary, when i.c.v. is the route of administration, a higher dose of CRF is required to induce autonomic and behavioral responses similar to those elicited by CRF injected into the LH/PFx. The cardiovascular and behavioral effects of LH/PFx-CRF indicate that this region may be an important site for central CRF to produce stress-related autonomic and behavioral responses. In addition, the CRF-induced effects, both in magnitude and onset, show site specificity, the caudal LH and perifornical area being more responsive to the peptide than the rostral LH and the area ventral to the Fx. As CRF-evoked behavioral activation does not necessarily coincide with changes in MAP and HR, our data suggest a dissociation of the peptide's central actions to influence behavioral and autonomic responses.

Animals↗
PubMed1991

Hypothalamic blood flow autoregulation remains unaltered following surgical and pharmacological blockade of central vasopressin.

Experiments were carried out in urethane anaesthetized, ventilated rats to determine if brain arginine-vasopressin (AVP) plays a physiological role in cerebral blood flow autoregulation. Autoregulation was tested by determining local hypothalamic blood flow in the mediobasal hypothalamic area (HBF; H2-gas clearance technique) during consecutive stepwise lowering of systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Endogenous AVP was blocked by transecting the rostral, lateral and dorsal neuronal connections of the hypothalamus (including the median eminence) from all major brain areas, by bilateral transection of the vasopressin-containing fibres in the hypothalamo-hypophyseal tract to the median eminence at the level of the lateral retrochiasmatic area (RCAL), and finally by intracerebroventricular (i.c.v.) administration of an AVP antagonist, d(CH2)5Tyr(Me)AVP (AAVP). Significant increases of daily water intake indicated impaired vasopressin release following both types of surgical transection. Resting HBF was significantly elevated both after surgical isolation of the hypothalamus and after 10 ng AAVP administration compared to controls. Blood flow autoregulation in the hypothalamic region was seriously impaired following surgical isolation of the hypothalamus. However, HBF autoregulation remained just as effective as that of the control rats following either selective bilateral transection of the vasopressin pathways or following AAVP treatment. The present data indicate that AVP may play a role in the control of resting hypothalamic blood flow, but does not support a role of AVP in HBF autoregulatory mechanisms.

Animals↗
PubMed1991

Interactive effects of neurohypophyseal neuropeptides with receptor antagonists on passive avoidance behavior: mediation by a cerebral neurohypophyseal hormone receptor?

The neurohypophyseal neuropeptides (Arg8)-vasopressin (AVP) and [pGlu4,Cyt6]AVP-(4-8) (where pGlu is pyroglutamic acid and Cyt is cystine) facilitate the retention of one-trial-learning passive avoidance behavior in rats when administered into the cerebral ventricle immediately after the learning trial. The fragment [pGlu4,Cyt6]AVP-(4-8) was considerably more effective than AVP. Oxytocin (OXT) and [pGlu4,Cyt6]OXT-(4-8) have the opposite effect and attenuate passive avoidance behavior also when administered into the cerebral ventricle after the learning trial. Again the fragment was more active than the parent molecule. The ancient arginine-containing neurohypophyseal hormone vasotocin in "high" doses (10ng) had a vasopressin-like effect and in "low" doses (0.1 ng) had an OXT-like effect on passive avoidance behavior. Because both vasopressinergic (V1) and oxytocinergic receptors have been demonstrated in the central nervous system, we asked whether specific antagonists of the V1, V2, and OXT receptor could antagonize the effects of these neuropeptides on passive avoidance behavior. The three antagonists were approximately equally active in blocking the effect of vasopressin, whereas the fragment [pGlu4]AVP-(4-8) and the high dose of vasotocin were more readily blocked by the OXT antagonist. The attenuating effect of OXT, the fragment [pGlu4,Cyt6]OXT-(4-8), and the low dose of vasotocin was markedly reduced by the OXT antagonist. This effect could also be reduced by pretreatment with the V1 antagonist but not with the V2 antagonist. These results suggest the existence of a separate neurohypophyseal hormone receptor complex in the brain affecting memory processes that differs from the peripheral V1, V2, and OXT receptor.

Animals↗
PubMed1991

Structural modifications of the ACTH-(4-9) analog ORG 2766 yields peptides with high biological activity.

The behavioral effects of two peptides (HOE 427) and ORG 31433) related to the ACTH-(4-9) analog ORG 2766 were investigated in Wistar rats in a number of tests in which Org 2766 is active. Subcutaneous administration of HOE 427 in a dose of 0.5 ng/kg or ORG 31433 in doses of 0.5-5.0 ng/kg facilitated passive avoidance behavior whereas these peptides attenuated the avoidance response in doses of 25 ng/kg and 250 ng/kg respectively. ORG 31433 (0.1 - 1.0 microgram/kg) decreased motor activity of group housed rats tested under low light conditions. Furthermore subcutaneous (1.0- 10.0 ng/kg) or oral (10 microgram/kg) administration of ORG 31433 accelerated functional recovery from 6-hydroxydopamine (6-OHDA)-induced lesions in the nucleus accumbens which cause motor hypoactivity. The experiments show that as compared to ORG 2766 the peptides HOE 427 and ORG 31433 induce qualitatively similar responses but are approximately 10 to 100 times more potent. These data may imply that substitution of the C-terminal COOH group of ORG 2766 yields neuropeptides with increased potency.

Administration, Oral↗
PubMed1991

Differential effects of emotional and physical stress on the central and peripheral secretion of neurohypophysial hormones in male rats.

The effects of various stressful conditions on the levels of oxytocin (OT) and vasopressin (VP) in plasma and cisternal cerebrospinal fluid (CSF) of male rats were investigated. Three experimental models were used: exposure to a novel environment for 5 min, immobilization for 15 min, and ether inhalation for 10 min resulting in anaesthesia. Novelty and immobilization induced a slight but significant increase in OT levels in the CSF immediately after the stress. The effect of ether was considerably more pronounced. The concentration of VP in the CSF was elevated only by ether stress. In plasma, the level of OT was increased immediately following immobilization and ether stress but not after novelty stress, whereas VP only showed a delayed response 20 min after immobilization. These results indicate a rapid preferential release of OT in the periphery in response to physical and pharmacological stress. In addition, they provide evidence that release of OT into the CSF is triggered by physical, pharmacological as well as emotional stress, while the central release of VP is rather resistant to emotional stress. The data suggest that OT is a stress hormone in the central nervous system.

Animals↗
PubMed1991

Epithelium-dependent potentiation of anaphylactic contractions by beta-endorphin in tracheae isolated from actively sensitized guinea-pigs.

1. It has been shown that opioid peptides modulate airway function. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea-pigs has been studied. 2. beta-Endorphin had a concentration-dependent bimodal effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (10(-10) and 10(-8) M) significantly potentiated anaphylactic contractions, whereas higher concentrations (10(-7) and 10(-6) M) significantly suppressed anaphylactic contractions of guinea-pig trachea. 3. beta-Endorphin in concentrations of 10(-8) M and 10(-7) M did not affect the responsiveness of the tracheal rings to histamine or leukotriene D4. This indicates that beta-endorphin does not influence the responsiveness of tracheal smooth muscle to anaphylactic mediators. 4. In the presence of the non-selective opioid receptor antagonist naloxone, 10(-8) M beta-endorphin still potentiated the anaphylactic contractions of the trachea. In addition, an equimolar concentration of des-Tyr1-beta-endorphin, a fragment of beta-endorphin without opioid-like activity, also potentiated anaphylactic contractions. The potentiation of anaphylactic contraction by 10(-8) M beta-endorphin is not therefore mediated by classical opioid-receptors. 5. In the presence of naloxone, 10(-7) M, beta-endorphin did not suppress anaphylactic contractions of the trachea. Thus, the suppression of anaphylactic contraction is mediated via a classical opioid-receptor. 6. In epithelium-denuded trachea, both 10(-8) and 10(-7) M beta-endorphin suppressed the anaphylactic contractions, whereas 10(-8) and 10(-7) M des-Tyr1-beta-endorphin did not affect anaphylactic contractions. It is concluded that the potentiation of the anaphylactic contraction in intact trachea is epithelium-dependent whereas the suppression of the anaphylactic contraction is epithelium-independent.

Anaphylaxis↗
PubMed1991

Autonomic and behavioral effects of centrally administered corticotropin-releasing factor in rats.

Changes in heart rate, core temperature, and gross locomotor activity were recorded simultaneously by a wireless telemetry system for periods up to 60 min after intracerebroventricular (icv) administration of synthetic human CRF-(1-41) (CRF) or artificial cerebrospinal fluid in rats in their home cages. The telemetry system provides a highly sensitive method to monitor autonomic nervous system (ANS) activity without imposing restraint on the animal. CRF was administered at lower doses than hitherto used to study central effects on the ANS (0.03, 0.1, 0.3, and 1 microgram). Starting 10 min after icv injections, behavioral responses to CRF, i.e. grooming, locomotion, and digging, were determined by a time sampling method. Within 5 min after icv treatment, CRF, in a dose-related fashion, produced a significant increase in heart rate, core temperature, and behavioral activity. The absence of effect of 30 ng CRF, which already may be regarded as a supraphysiological amount, suggests that CRF does not modify ANS and behavioral activity under resting conditions. Tachycardiac responses in rats receiving 0.1 microgram CRF, icv, in the morning were more marked than those in rats given the same treatment in the late afternoon. In addition, the presumed intrinsic activity of the CRF receptor antagonist, alpha-helical CRF-(9-41) (alpha hCRF) at doses of 0.1, 1, 5, and 25 micrograms was evaluated. Intracerebroventricular injections of 0.1 and 1 microgram alpha hCRF failed to produce detectable effects. At the 5- and 25-micrograms doses, alpha hCRF dose-dependently induced tachycardia and behavioral activation, suggesting partial agonistic activity. Taken together, these results demonstrate that CRF does not play a role in the regulation of ANS and behavioral activity under resting conditions. The responses produced by icv injected supraphysiological amounts of CRF, however, may serve to model a stressful situation during which the massively released CRF induces similar effects on ANS and behavior, after reaching high local concentrations at brain sites involved in the mediation of these actions.

Animals↗
PubMed1990

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↗
PubMed1990

Neurotrophic effects of ACTH/MSH neuropeptides.

Numerous experiments with peptides related to ACTH/MSH, and involving tests such as avoidance, approach, discrimination and rewarded behavior indicate that these peptides possess neuroactive effects on learning, motivation, attention, and concentration. In addition, ACTH/MSH neuropeptides affect social behavior, interact with opiate binding sites, and possess antiepileptic properties. Other CNS effects which can be demonstrated after intracranial administration only are grooming behavior, stretching, yawning and sexual behavior. The effects reside mainly in the N-terminal part of ACTH (ACTH-(4-10); ACTH-(7-16) and are dissociated from the peripheral corticotrophic effect. Several substitutions in the sequence ACTH-(4-9) led to a highly selective, potent and orally active neuropeptide with a marked loss of endocrine effects. Thus H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) appeared to be 1,000 times more active on avoidance behavior than ACTH-(4-10) but to contain 1,000 times less melanotrophic activity. It also had a markedly reduced steroidogenic, fat mobilizing and opiate-like activity. ACTH/MSH peptides also possess neurotrophic activities as derived from studies on regeneration of damaged nerve cells. Animal studies show beneficial effects of semichronic treatment of the ACTH-(4-9) analogue Org 2766 on nerve crush regeneration in animals. The activity for this effect resides in the sequence ACTH-(6-10). The neurotrophic influence is evident both at the sensory and the motor function level. The protective effect of Org 2766 is also found in other neuropathies as a result of diabetes mellitus and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1979

Effect of oxytocin and vasopressin on memory consolidation: sites of action and catecholaminergic correlates after local microinjection into limbic-midbrain structures.

The effects of local postlearning microinjections of arginine-vasopressin (AVP) and oxytocin (OXT) on one-trial learning passive avoidance behavior and the influence of AVP on alpha-MPT-induced disappearance of norepinephrine (NE) and dopamine (DA) in discrete brain regions have been studied in the rat. OXT injected bilaterally in the hippocampal dentate gyrus (25-25 pg) or in the midbrain dorsal raphe nucleus (50 pg) significantly attenuated passive avoidance behavior. Facilitation of passive avoidance behavior was observed when the peptide was injected into the dorsal septal nucleus. AVP facilitated passive avoidance behavior when administered into the hippocampal dentate gyrus, dorsal raphe nucleus or dorsal septal nucleus. Injection of either neuropeptides into the central amygdaloid nucleus appeared to be ineffective. One week after the behavioral experiments a repeated injection of AVP into the hippocampal dentate gyrus increased the disappearance of NE in the dentate gyrus and in the nucleus ruber. An injection into the dorsal septal nuclei decreased the NE disappearance in the dorsal septal nucleus itself and increased it in the nucleus ruber. Injection in the dorsal raphe nucleus led to an increase in the disappearance of DA in the locus coeruleus and in the nucleus ruber. It is concluded that memory consolidation can be oppositely influenced by local application of minute amounts of either OXT or AVP into certain limbic-midbrain structures, suggesting an involvement of these brain regions in the memory effects of these peptides. Modulation of catecholamine turnover in specific brain areas after AVP administration may be related to this behavioral effect.

Animals↗