Biomedical subjects

D De Wied

Publications and source records attributed to D De Wied.

At least 55 records · Page 3Linked to original sources

PubMed1986

Desenkephalin-gamma-endorphin restores the impaired sensitivity of hypophysectomized rats to small doses of apomorphine.

Hypophysectomized male rats, tested 7 days after removal of the pituitary, showed a reduced sensitivity to small doses of apomorphine. In these rats, subcutaneous (s.c.) treatment with apomorphine (25, 100 or 250 micrograms/kg) did not elicit any reduction in locomotor activity measured 5 min after injection in contrast to that observed in sham-operated control rats. The enhancement of locomotor activity and stereotyped behavior, 20 min after the s.c. administration of apomorphine, was similar in hypophysectomized rats and in control animals. Prolactin does not seem to be implicated in this altered sensitivity, since hyperprolactinaemia induced by pituitary homografts under the kidney capsule did not change the response to apomorphine in hypophysectomized rats. Chronic treatment with desenkephalin-gamma-endorphin (DE gamma E), a beta-endorphin fragment with neuroleptic-like properties, administered s.c. twice a day for 7 days at the dose of 10 micrograms/rat, restored the sensitivity to small doses of apomorphine in the hypophysectomized rats. The data suggest that removal of the pituitary leads to impaired sensitivity of presumably presynaptically located dopamine receptors mediating the effects of small doses of apomorphine without altering the sensitivity of postsynaptically located dopamine receptors that mediate the hypermotility and stereotypy induced by apomorphine. This impaired sensitivity to low doses of apomorphine could be restored by DE gamma E but not by prolactin, supporting the conclusions from previous experiments that DE gamma E and prolactin may selectively interfere with pre- and postsynaptic dopamine receptors respectively.

Animals↗

PubMed1986

Facilitation of avoidance behavior by vasopressin fragments microinjected into limbic-midbrain structures.

Effects of arginine vasopressin (AVP1-9) and its behaviorally active fragments [Cyt6]AVP5-9 and [Cyt6]AVP5-8 were studied on the retention of one-trial learning passive avoidance behavior in rats. Peptides were microinjected into various limbic and midbrain structures (ventral or dorsal hippocampus or the dorsal raphe nucleus) and were administered either immediately after the learning trial (post-learning treatment) or shortly before the 24 h retention session (pre-retention treatment). Doses for intracerebral microinjections were selected after preliminary experiments with subcutaneous and intracerebroventricular peptide administration. AVP1-9 facilitated passive avoidance behavior when the peptide was microinjected into either brain structure, however, the ventral hippocampus appeared to be the most sensitive. In this limbic region, AVP1-9 facilitated passive avoidance behavior in an amount of 8 pg (bilaterally), both when given as post-learning or pre-retention treatment. [Cyt6]AVP5-9 and [Cyt6]AVP5-8 were more effective than the parent nonapeptide in terms that a lower amount of these peptide fragments facilitated passive avoidance behavior in all brain regions investigated. The ventral hippocampus appeared to be the most sensitive brain site for the behaviorally active vasopressin fragments as well. Following microinjections into the ventral hippocampus, [Cyt6]AVP5-8 was more effective in a post-learning than in a pre-retention treatment schedule. [Cyt6]AVP5-9 on the other hand was more effective when injected shortly before the retention trial. The data indicate that limbic-midbrain structures are sensitive to AVP1-9 and behaviorally active putative metabolites of this neuropeptide. The active fragments selectively influence different phases of information processing upon limbic microinjections.

Animals↗

PubMed1986

Time-related memory effects of vasopressin analogues in rats.

The present study was designed to investigate critical time periods for the memory modulating effect of vasopressin and several analogues in rats using a passive avoidance test as the behavioral paradigm. AVP, AVP-(4-8) and AVP-(5-8) were more effective when given immediately after the learning trial (consolidation), while AVP-(1-8) (DGAVP) and AVP-(5-9) were more active when administered one hour prior to the retention test (retrieval). DDAVP and AVP-(4-9) were highly active both when given immediately after the learning trial or 1 hour before the retention test. The period between 12 and 18 hr after the learning trial appeared to be another sensitive period. Administration, in particular of DGAVP, and AVP-(5-9) at 12, 15, and 18 hr after the learning trial induced marked retention of the avoidance response at the 24 hr retention test. Injection at 6 and 21 hr after the learning trial was the least effective in facilitating passive avoidance latencies. The more stable analogue DDAVP facilitated avoidance latencies irrespective of the time of administration. Vasopressin and related peptides exert a long term effect on avoidance behavior. However, DGAVP and AVP-(5-9) facilitated passive avoidance behavior at the 24, 48, and 72 hr retention test if administered immediately after the learning trial. If injection was postponed till 15 hr after the learning trial, passive avoidance behavior was facilitated at the 24 hr retention test only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Effect of vasopressin, oxytocin and peptides derived from these hormones on field potential induced in lateral septum of rats by stimulation of the fimbria fornix.

Superfusion of the dorsal surface of the septum with artificial cerebrospinal fluid containing 10(-10) M [Arg8]-vasopressin (VP) significantly increased the negative (N) wave in field potentials (FPs) elicited in the lateral septum (LS) of rats by stimulation of the fimbria-fornix. A similar increase in the FPs negativity was also observed following superfusion of the septum with [pGlu4, Cyt6] VP(4-9), [pGlu4, Cyt6] VP(4-8), [Cyt6] VP (5-9), desglycinamide9-VP and 1-deamino, 8-D-arginine-VP. However, for obtaining the effect with these peptides 10(3-4) times higher concentrations had to be used. Superfusion of the septum with 10(-8) M oxytocin (OX) elicited nearly the same N-wave increase as the 10(-8) M VP septal superfusion. The 10(-10) M concentration of OX as well as 10(-7) M [pGlu4, Cyt6] OX(4-9) and [pGlu4, Cyt6] OX(4-8) had little effect on the FPs negativity. The significance of these findings for the elucidation of the VP function in the LS is discussed.

Animals↗

PubMed1986

Effect of the opioid peptide beta-endorphin on the in vivo release of vasopressin in rats under various conditions.

beta-Endorphin (beta E) exerts a strong inhibitory action on plasma vasopressin (VP) of rats, after intracerebroventricular, but not after subcutaneous injection of the drug. This effect is time- and dose-dependent. Also in the water-deprived rat, this treatment leads to a strong decrease of plasma VP levels. When rats treated with histamine (HIS) intracerebroventricularly to stimulate VP levels are injected with beta E to HIS treatment, beta E partially prevents the increase of plasma VP levels. Naloxone subcutaneously administered, antagonizes the effect of beta E in all the situations we investigated. Opioid receptors, located in the brain as well as in the pituitary, are possibly involved in these processes.

Animals↗

PubMed1985

Hypothalamic neuropeptides and memory.

Vasopressin and oxytocin exert pronounced effects on behavior by a direct action on the brain. A single injection of vasopressin results in a long-term inhibition of extinction of a conditioned avoidance response suggesting that vasopressin triggers a long-term effect on the maintenance of a learned response, probably by facilitation of memory processes. In addition vasopressin improves passive avoidance behavior, facilitates retention of sexually motivated T-maze choice behavior in male rats, delays extinction of an appetitive discrimination task, affects approach behavior to an imprinting stimulus in ducklings, delays the postcastration decline in copulatory behavior in male rats, prevents or reverses amnesia induced by electroconvulsive shock, CO2 inhalation, pentylenetetrazol or puromycin. The majority of these effects may be explained by stimulatory influences of vasopressin on memory processes. Generally oxytocin exerts effects which are opposite to those of vasopressin and it has been suggested that oxytocin may be an amnesic neuropeptide. Evidence has been obtained that endogenous vasopressin and oxytocin play a physiological role in brain processes related to memory. Various limbic system structures seem to act as the anatomical substrate for the behavioral effects of vasopressin and different neurotransmitter systems seem to be involved. It is postulated that in case vasopressin affects retrieval processes the site of action is located in the amygdala and the dentate gyrus of the hippocampal complex with dopamine and serotonin as the respective neurotransmitter systems involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Structure-activity studies with ACTH/alpha-MSH fragments on corticosteroid secretion of isolated zona glomerulosa and fasciculata cells.

The steroidogenic action of ACTH/alpha-MSH fragments was studied on isolated zona glomerulosa and zona fasciculata cells dispersed by collagenase. ACTH-(4-7), ACTH-(6-10), ACTH-(4-10) and ACTH-(11-13) stimulated corticosterone production of the zona fasciculata and aldosterone production of the zona glomerulosa cells. ACTH-(7-10) was ineffective. ACTH-(4-7) appeared to be the most potent peptide of the tested fragments. None of the fragments affected the steroidogenic action of ACTH-(1-39). It is suggested that similar to the melanotropic effect of alpha-MSH two 'message' sequences for adrenocortical stimulation exist in the alpha-MSH part of the ACTH molecule.

Adrenal Cortex↗

PubMed1985

Vasopressin and related peptides: animal and human studies.

In animals, vasopressin and related peptides are present in specific neuronal pathways in the brain and modulate brain processes. It has been suggested that in particular memory processes, including consolidation and retrieval, short and long term memories are facilitated by vasopressin. Evidence has been presented that endogenous vasopressin is involved in these processes. But also other effects of these peptides e.g. an attenuation of acquisition of heroin self-administration have been reported. Vasopressin and related peptides have been administered to humans in a number of studies including volunteers and various patient populations with and without complaints about memory. Beneficial effects on several aspects of memory, learning, attention and concentration have been found, but not in all studies. Patients with severe deficits seem to benefit less from the peptide treatment. This may be related to the amount of brain damage. Beneficial effects of vasopressin treatment have been reported in schizophrenics and heroin addicts. In addition effects on social behavior, energy and mood of certain patients have been noted. The target patient population for vasopressin neuropeptide is thus not yet well defined. With respect to cognitive disorders, sophisticated neuropsychological test procedures, including information-processing tasks, may contribute to define such a patient population. These tasks may also be applied for treatment evaluation. It should however be kept in mind that other interesting influences of vasopressin e.g. on social behavior, mood and addictive behavior, may also appear of clinical significance. Future studies in humans may yield more detailed information in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnesia↗

PubMed1985

Gamma-type endorphins: neurolepticum-like and antipsychotic action.

The hypothesis implicating the gamma-type endorphins in schizophrenia was initially based on animal data showing commonalities between the behavioral effects of these peptides and neuroleptics. Clinical studies have shown that these peptides have an antipsychotic action in a number of patients suffering from schizophrenic psychosis. The patients responding to the peptides are characterized by features at least partly resembling those characterizing type I schizophrenia. This may be consistent with the animal data showing that gamma-type endorphins may directly or indirectly control certain dopaminergic systems present in the nucleus accumbens. Genetical differences may exist between patients susceptible to and not susceptible to gamma-type endorphins, as has been concluded from studies concerning antigens of the HLA system.

Antipsychotic Agents↗

PubMed1985

Beneficial effect of chronic treatment with Org 2766 and alpha-MSH on impaired reversal learning of rats with bilateral lesions of the parafascicular area.

The effects of chronic treatment with the ACTH-(4-9) analogue Org 2766, alpha-MSH, and gamma 2-MSH were studied on T-maze reversal learning and on behavior assessed on the basis of open-field and other gross behavioral activities, grasping responses, inspection of various reflexes and electrical footshock sensitivity of rats with parafascicular lesions or sham-lesions. Repeated administration of Org 2766 and alpha-MSH to parafascicular area-lesioned rats resulted in functional recovery of impaired T-maze reversal learning. The structurally related neuropeptide gamma 2-MSH was without any effect. The alpha-MSH effect did not depend on time after lesioning as treatments during the first or second post-operative week were equally effective. Chronic peptide treatments did not change disturbed motor functions of parafascicular-lesioned rats, as measured by open-field activity, other gross behavioral activities and grasping responses. Since acute peptide treatments did not affect the impaired reversal learning performance of lesioned rats, the beneficial effect of Org 2766 and alpha-MSH could not be explained as a short-term effect on attention and motivation. It was more likely to be an accelerated recovery of cognitive function as a result of long-term neurotropic influences.

Adrenocorticotropic Hormone↗

PubMed1984

Substances resembling C-terminal vasopressin fragments are present in the brain but not in the pituitary gland.

In order to investigate the endogenous occurrence of vasopressin fragments that have previously been found to be generated in vitro by brain peptidases and to have highly potent central activity, extracts of hypothalamus, hippocampus and the pituitary gland were fractionated by high pressure liquid chromatography and analyzed by radioimmunoassay systems with different specificities. Substances that were immunologically and chromatographically similar to synthetic C-terminal vasopressin fragments were detected in brain tissue in different amounts, but were virtually absent in the pituitary gland. It is suggested that these components may represent endogenous vasopressin metabolites. The preferential presence in brain supports a selectively central function of these peptides.

Arginine Vasopressin↗

PubMed1984

Pre-decapitation state of arousal of rats predetermines the effect of des-Tyr1-gamma-endorphin on dopamine release from nucleus accumbens slices in vitro.

The non-opiate beta-endorphin fragment des-Tyr1-gamma-endorphin (DT gamma E) had a decreasing effect on K+-induced release of tritiated dopamine from nucleus accumbens slices in vitro, when tissue was used of rats which prior to decapitation were in a state of low arousal. When nucleus accumbens tissue was used of rats which were mildly stressed by exposure to a novel environment prior to decapitation, this effect was absent, while an enhancing effect of DT gamma E became evident on basal dopamine efflux. This latter effect resembled that of haloperidol, which dose-dependently enhanced basal dopamine efflux in vitro. Exposure of rats to ether vapor shortly before decapitation abolished both these in vitro effects of DT gamma E. The results are interpreted as indicating that the quality of the modulating effects of DT gamma E on dopamine release from dopaminergic neurons projecting to the nucleus accumbens is depending on the state of activity of these neurons, which, in its turn, is a reflection of the state of arousal of the rats.

Animals↗

PubMed1984

Microinjection of vasopressin and two related peptides into the amygdala: enhancing effect on local dopamine neurotransmission.

The effects of local microinjection of Arg8-vasopressin, cyclo[Lys-Gly] and L-Pro-L-Leu-GlyNH2 (PLG) were studied on the alpha-MPT-induced disappearance of dopamine and noradrenaline in the amygdala and in a number of other brain regions. A dose-dependent increase in dopamine utilization was found in the amygdala after local microinjection of Arg8-vasopressin, cyclo[Lys-Gly] and PLG at doses of 0.1, 2.7 and 18 pmol respectively. No effects were found on noradrenaline utilization in this brain region. Using a microdissection method, it was found that cyclo[Lys-Gly] enhanced dopamine utilization in the nucl. amygdaloideus centralis, whereas the effect of PLG was mainly located in the nucl. amygdaloideus corticalis. These effects of Arg8-vasopressin, cyclo[Lys-Gly] and PLG on dopamine utilization in the amygdala are correlated with those on avoidance behavior and can be interpreted as in support of the role of dopamine as neurotransmitter involved in retrieval processes.

Amygdala↗

PubMed1984

Differential behavioral actions of corticotropin-releasing factor (CRF).

In order to elucidate the involvement of the 41 amino-acid residue corticotropin-releasing factor (CRF) in the modulation of brain functioning, the behavioral profile of the releasing hormone was determined using tests for spontaneous behavior, grooming, active and passive avoidance behavior. Intracerebroventricular (ICV) administration of CRF in a dose that does not stimulate the pituitary-adrenal axis, resulted in an activation of open-field behavior, as measured by ambulation and rearing activities. Also grooming activity was significantly enhanced after central application of CRF. In hypophysectomized rats, which show an impaired shuttle-box avoidance acquisition, CRF restored acquisition for the duration of the treatment. Paradoxically, extinction of pole-jumping active avoidance behavior of intact rats was facilitated by the releasing factor, even in adrenalectomized animals. Passive avoidance behavior was affected bidirectional: higher doses of CRF (300 ng), given subcutaneously (SC), attenuated passive avoidance retention, probably via activation of the pituitary-adrenal system resulting in high corticosterone levels. Lower doses (30 ng), however, which were also given SC did not stimulate pituitary-adrenal activity, and facilitated retention of passive avoidance behavior. Central administration of CRF in very low doses (30 pg) had the same effect as higher doses of CRF given SC, i.e., inhibition of passive avoidance retention. Taken together, the data indicate that CRF can affect behavior via a direct action on the central nervous system. The question remains whether this activity is an intrinsic property of CRF, or mediated by the release of hormones or neuropeptides.

Adrenalectomy↗

PubMed1984

Vasopressin antagonists block peripheral as well as central vasopressin receptors.

The aim of the present study was to differentiate between the postulated central behavioral effects of vasopressin and its pressor response, which is mainly mediated by peripheral vascular receptors. Thus, the interaction between the vasopressor antagonists dPTyr(Me)AVP (AAVPa) and d(CH2)5Tyr(Me)AVP (AAVPb) with the effects of [Arg8]vasopressin (AVP-(1-9)) and [pGlu4,Cyt6]AVP-(4-8) (referred to as AVP-(4-8)) was examined using passive avoidance behavior and the pressor response as parameters. AVP-(4-8) was approximately 4 and 200 times more potent than AVP-(1-9) in facilitating passive avoidance behavior after subcutaneous (SC) or intracerebroventricular (ICV) administration respectively. This effect of SC injected AVP-(1-9) and AVP-(4-8) could be prevented by both vasopressor antagonists following SC treatment. A similar antagonistic action was found when AVP-(1-9) or AVP-(4-8) and the antagonist AAVPb were administered ICV. SC injection of AAVPb prevented the behavioral effect of ICV administered AVP-(1-9) while ICV treatment with the antagonist blocked the behavioral action of systemically injected AVP-(1-9) and AVP-(4-8). In contrast to SC injected AVP-(1-9) which dose-dependently increased blood pressure and decreased heart rate, AVP-(4-8) injected SC in identical doses did not affect blood pressure and heart rate, neither did AVP-(1-9) and AVP-(4-8) when injected ICV in behaviorally active doses. A SC, but not an ICV injection of the antagonist AAVPb could prevent the blood pressure increase and bradycardia induced by SC AVP-(1-9).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Differential responses to osmotic stress of vasopressin-neurophysin mRNA in hypothalamic nuclei.

mRNA encoding the vasopressin-neurophysin precursor was quantitated in individual hypothalamic nuclei of rats by a liquid hybridization assay. Drinking of 2% saline for 14 days, a treatment that increased the plasma vasopressin concentration 9-fold, resulted in a 5- and 2-fold increase in mRNA levels in the supraoptic and paraventricular nucleus, respectively. This osmotic stimulus had no effect on vasopressin-neurophysin mRNA content of the suprachiasmatic nucleus. This dissociation in regulation of vasopressin-neurophysin mRNA in hypothalamic nuclei indicates the existence of two separate vasopressin systems that are independently activated.

Animals↗

PubMed1983

Arginine-vasopressin content of hippocampus and amygdala during passive avoidance behavior in rats.

Arginine-vasopressin (AVP) is involved in memory processes. The memory effects of AVP are mediated by neuronal mechanisms taking place in limbic-midbrain structures. Therefore, immunoreactive AVP (IR-AVP) was measured in hippocampus and amygdala of male Wistar rats during acquisition and retention of passive avoidance behavior. IR-AVP concentration was decreased in the hippocampus immediately after the learning trial while IR-AVP content of the amygdala was not affected. Animals that showed the passive avoidance response (good avoiders) at the 24 h or 120 h retention test had a reduced IR-AVP concentration in the hippocampus immediately after the test. However, IR-AVP content of the hippocampus was not different from that of non-shocked control animals when measured immediately before the 120 h retention test. Poor avoiders that showed only minor avoidance behavior did not differ in hippocampal IR-AVP content from non-shocked control animals. IR-AVP content of the amygdala was also not altered after the retention session. These effects on IR-AVP content could only be shown in animals that were trained and habituated to the passive avoidance procedure. Such trained and habituated animals had an IR-AVP level in the hippocampus which did not differ from that of animals that were left undisturbed until sacrifice. When the animals were not trained, but placed for the first time in the passive avoidance apparatus without being exposed to the learning trial, the hippocampal IR-AVP content was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

PubMed1983

Oxytocin is a precursor of potent behaviourally active neuropeptides.

An oxytocin fragment which accumulated during the incubation of oxytocin with brain synaptic membranes was chemically characterized as the hexapeptide pGlu-Asn-Cys(Cys)-Pro-Leu-Gly-NH2 [( pGlu4, Cyt6]OXT-(4-9]. This peptide was approximately a hundred times more potent than oxytocin in attenuating memory consolidation as tested in a passive avoidance test situation; the dose-response relationship was bell-shaped. The des-glycinamide derivative [pGlu4, Cyt6]OXT-(4-8) was nearly as active, but showed a linear dose-response relationship. The data indicate that oxytoxin can act as precursor for potent behaviourally active neuropeptides.

Animals↗