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Biomedical subjects

T B van Wimersma Greidanus

Publications and source records attributed to T B van Wimersma Greidanus.

At least 19 recordsLinked to original sources

The role of limbic vasopressin and oxytocin in social recognition.

Young male rats were exposed two times for 5 min, to older male rats with an interval of 30 min in the anti-vasopressin serum experiments and with an interval of 120 min in the anti-oxytocin serum experiments. The time spent by the older rats with social investigation of the younger animal was scored during the two encounters. In placebo-treated animals the time spent on social investigation of the younger animal during the second encounter at 30 min is significantly shorter than during the first one (social recognition). However, intracerebroventricular or local application of anti-vasopressin serum in the dorsal or ventral hippocampus or in the dorsal septal area, but not in the n. olfactorius, results in similar periods of time spent for social investigation during the two encounters. Thus, endogenous vasopressin in the dorsal and ventral hippocampus and in the dorsal septal region plays a physiological role in social recognition/memory. In placebo-treated rats the time spent on social investigation of the younger animal during the second encounter at 120 min is similar to that during the first encounter. However, local administration of anti-oxytocin serum in the ventral hippocampus, but not in the dorsal hippocampus, nor in the n. olfactorius or the septal area, results in shorter investigation times during the second encounter. Thus, taken together the presence or local release of vasopressin and oxytocin in the ventral hippocampus and that of vasopressin (but not oxytocin) in the dorsal hippocampus and dorsal septal area are of physiological importance for social recognition.

Animals↗

Effect of central administration of the kappa-opiate receptor agonist U 69.593 on neurohypophyseal hormone levels in blood and cerebrospinal fluid.

Intracerebroventricular (i.c.v.) administration of the kappa-opiate receptor agonist U 69.593 induces a rapid and short lasting suppression of oxytocin (OXT) levels in plasma of water deprived rats, whereas only a tendency towards a suppression of vasopressin (AVP) levels in plasma is observed. No change in neurohypophyseal hormone levels in CSF occurs following i.c.v. administration of U 69.593 at the various times points studied. It is concluded that, upon i.c.v. administration, the suppressive influence of U 69.593 is much weaker than that of the dynorphins and that neurophypophyseal hormone levels in CSF behave differently from those in the peripheral circulation.

Analgesics↗

Dynorphin-A and vasopressin release in the rat: a structure-activity study.

The effects on vasopressin (VP) release of three dynorphin-A fragments and two antidynorphin antisera were tested in vivo and in vitro. In vivo, the order of potency to inhibit VP release 30 min upon i.c.v. injection was: dynorphin-A-(1-17) > dynorphin-A-(1-13) > dynorphin-A-(1-8). l.c.v. co-administration of 10 nmoles of the specific endopeptidase-inhibitor cFPAAF-pAB and dynorphin-A-(1-8) also suppressed VP secretion. Dynorphin-A-(1-17) antiserum enhanced VP release 20 and 60 min after i.c.v. injection. The antiserum that recognized dynorphin-A-(1-13) elevated VP plasma levels at 60 min post-injection. In vitro, dynorphin-A-(1-8) suppressed electrically evoked VP release from the isolated neural lobe. VP release was not affected by dynorphin-A-(1-13), dynorphin-A-(1-17), naloxone, or by the anti-dynorphin antisera. These data indicate that dynorphin-A-(1-17), rather than dynorphin-A-(1-8), plays a role in the centrally located control of neurohypophysial VP release, whereas dynorphin-A-(1-8) is involved in the control located in the posterior pituitary. The synthetic intermediate fragment dynorphin-A-(1-13) appears to affect VP release both centrally and peripherally.

Analysis of Variance↗

Vasopressin levels in the cerebrospinal fluid of rats with lesions of the paraventricular and suprachiasmatic nuclei.

The circadian rhythm and dehydration-induced response of vasopressin (AVP) levels in rat cerebrospinal fluid (CSF) were studied after lesions had been made in the paraventricular (PVN) and suprachiasmatic (SCN) nuclei. The rhythmic fluctuation of AVP levels in CSF was abolished after SCN lesions, whereas lesions of the PVN had no effect. Dehydration seems to increase AVP levels in CSF of both sham-operated and lesioned animals. These data further suggest that the circadian rhythm of AVP in CSF is preferentially generated by SCN. In contrast, several areas of the brain may contribute to the overall AVP levels in CSF, both under normal physiological conditions and under osmotic stress.

Animals↗

Volume-regulated arginine vasopressin release in conscious dogs. Evidence for dopaminergic or opioid modulation?

The possibility of a dopaminergic and/or opioid modulation of the volume-regulated release of AVP was investigated in conscious dogs. Either bromocriptine, 10 micrograms/kg body weight po, or naloxone, 0.1 mg/kg body weight iv, was administered prior to induction of nonhypotensive hypovolemia. Volume contraction of 15 ml/kg body weight was induced gradually, over a period of 30 min. Basal plasma AVP levels in the bromocriptine group were not significantly different from control group values. Bromocriptine administration significantly augmented AVP release following volume contraction. Mean arterial pressure in the bromocriptine group decreased to a slightly, but significantly, lower level than that in the control group. Mean arterial pressures, however, did not adequately explain the magnitude of the AVP response in the bromocriptine group. In the naloxone group, neither baseline levels, nor AVP values following volume contraction, differed significantly from respective control group values. In conclusion, the results suggest the possibility of a stimulatory role for endogenous dopamine in the volume-regulated, but not the basal, release of AVP in conscious dogs.

Animals↗

Microinjection of anti-vasopressin serum into limbic structures of the rat brain: effects on passive avoidance responding and on local catecholamine utilization.

Rats which had received bilateral microinjections of 1:50 diluted anti-vasopressin serum into the dorsal or ventral hippocampus, immediately after the learning trial of a one-trial passive avoidance test, showed a reduction in avoidance latency scores during subsequent retention tests 24 and 48 h later. Postlearning microinjection of anti-vasopressin serum into either the dorsolateral septum or the caudate nucleus was without effect on the retention of passive avoidance behavior. Microinjection of anti-vasopressin serum 1 h before the 24-h retention session into either the dorsal hippocampus, the ventral hippocampus or the dorsolateral septum attenuated avoidance responding during both the 24-h and 48-h retention sessions, whereas preretention microinjection of the serum into the caudate nucleus was not effective. Intracerebroventricular administration of the anti-vasopressin serum in amounts similar to those used in the microinjection experiments did not affect retention scores when given either immediately after the learning trial or before the first retention session. One week after the behavioral experiments, a repeated microinjection of anti-vasopressin serum decreased the local alpha-methyl-p-tyrosine methylester (alpha-MPT)-induced disappearance of noradrenaline in the ventral hippocampus and the dorsal hippocampus respectively. Microinjection of the antiserum in the dorsolateral septum enhanced noradrenaline disappearance in this brain region. No effect was found on alpha-MPT-induced dopamine disappearance in the caudate nucleus following local microinjection of anti-vasopressin serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dynorphin-(1-13) is a potent in vivo suppressor of vasopressin levels in the rat.

Intracerebroventricular administration of dynorphin-(1-13) inhibits dose-dependently plasma vasopressin level in normal as well as in water-deprived rats, whereas systemic (subcutaneous) administration of this opioid peptide is ineffective in this respect. Simultaneous subcutaneous, but not intracerebroventricular, administration of naloxone prevents the suppressive effect of dynorphin-(1-13) on plasma vasopressin levels.

Animals↗

The influence of neurotensin, naloxone, and haloperidol on elements of excessive grooming behavior induced by ACTH.

Naloxone, haloperidol, and neurotensin suppress ACTH-induced grooming. The suppressive effects of naloxone and of haloperidol on ACTH-induced grooming are observed following subcutaneous as well as intracerebroventricular administration. The suppression of ACTH-induced grooming by these drugs is not accompanied by a change in the relative distribution of grooming elements. From previous data and from the results of the present study it is suggested that the underlying substrate involved in ACTH-induced excessive grooming may differ from that of bombesin-induced grooming.

Adrenocorticotropic Hormone↗

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↗

Vasopressin levels in the cerebrospinal fluid in rats of different age and sex.

In male and female rats of two different age groups, we measured the arginine-vasopressin (AVP) levels in cerebrospinal fluid (CSF) collected at different times of the day. Mean values of AVP in cisternal CSF averaged across the different times of the day were higher in males than in females (p = 0.02), and in young (2 months) than in aged (12 months) rats (p = 0.03) of both sexes. The AVP levels in CSF showed a clear circadian rhythm in both young and aged male rats; the values at 07.00 h and 13.00 h were higher than those at 01.00 h and 19.00 h. The amplitude of the rhythm was smaller in females than in males. In addition, the rhythm was more pronounced in young than in aged rats of both sexes. These data suggest that both age and sex affect levels of vasopressin in CSF.

Aging↗

Vasopressin and oxytocin. Their presence in the central nervous system and their functional significance in brain processes related to behaviour and memory.

Vasopressin and oxytocin exert pronounced effects on behaviour 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 behaviour, delays extinction of appetitive discrimination tasks, affects approach behaviour to an imprinting stimulus in ducklings, improves copulation rewarded behaviour of male rats in a T-maze, prevents or reverses amnesia induced by electroconvulsive shock, CO2 inhalation, pentylenetetrazol or puromycin. The majority of these effects of vasopressin in the various and sometimes relatively complex tasks may be explained by stimulatory influences of this neuropeptide 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. Various limbic system structures seem to act as the anatomical substrate for the behavioural effects of vasopressin. In particular the amygdala, the dentate gyrus of the hippocampal complex, the ventral hippocampus and the dorsal septum seem to be involved. Evidence has been obtained from experiments with homozygous diabetes insipidus rats and from experiments in which antisera were applied that endogenous vasopressin and oxytocin play a physiological role in brain processes related to memory. It appears that highly active fragments can be generated from vasopressin and experiments in which a fragment of vasopressin ([pGlu4, Cyt6]AVP-(4-8)) as well as an AVP-antagonist were used, reveal that the vasopressin receptors mediating the behavioural effects are situated in the brain and differ in specificity from the peripheral (blood pressure) vasopressin receptors. Generally the clinical data obtained so far with vasopressin treatment are in agreement with the results from animal experiments and they support the notion on the involvement of vasopressin in memory function. The sometimes reported conflicting results on vasopressin effects in certain patients (Korsakoff or Alzheimer) may have to do with the wide-spread pathology in these diseases.

Animals↗

Effects of naloxone and neurotensin on excessive grooming behavior of rats induced by bombesin, beta-endorphin and ACTH.

Bombesin, beta-endorphin and ACTH-(1-24) induce excessive grooming behavior in rats. Whereas ACTH increases the frequency of all components of grooming behavior (head washing, bodily grooming and paw licking), the most pronounced element of bombesin- and beta-endorphin-induced excessive grooming is scratching. Naloxone counteracts peptide-induced grooming and in particular excessive scratching is reduced by this opiate antagonist. Also neurotensin suppresses peptide-induced grooming behavior and in particular scratching. It is concluded that the element scratching is the component of grooming behavior which is mainly displayed by activation of opiate receptors and that neurotensin is able to interfere with opiate receptor mediated behavior.

Animals↗

Ethanol increases plasma vasopressin shortly after intraperitoneal injection in rats.

In rats, ethanol has generally been thought to inhibit vasopressin (VP) release into the peripheral circulation; however, the primary evidence for this conclusion has been indirect. Radioimmunoassay was used to measure VP in the plasma of rats decapitated 5 or 60 min after intraperitoneal injection of ethanol (2.0 g/kg). Confirming the popular notion that ethanol inhibits VP release, VP levels were decreased 60 min after treatment. But radioimmunoassay techniques also revealed that VP release is markedly stimulated shortly after an injection of ethanol.

Animals↗

The effect of gamma-type endorphins on alpha-MSH release in the rat.

Neuroleptic drugs increase the level of alpha-melanotropin (alpha-MSH) in the blood of the rat. We have investigated whether neuroleptic-like peptides, the gamma-type endorphins, also affect alpha-MSH release. A structure-activity study revealed that (des-enkephalin)-gamma-endorphin (DE gamma E, beta-LPH-(66-77), beta-endorphin-(6-17)) is able to increase plasma alpha-MSH levels after intracerebroventricular injection, while the longer gamma-type endorphins, i.e. gamma E (beta-LPH-(61-77)), beta-endorphin-(1-17)), and DT gamma E (beta-LPH-(62-77), beta-endorphin-(2-17)) were without effect in the dosage used. A dose-response study revealed a more or less bell-shaped relationship for the effect of DE gamma E on plasma alpha-MSH levels. The effect of DE gamma E could not be counteracted by apomorphine or naloxone. The observations indicate that DE gamma E increases plasma alpha-MSH levels in a way distinct from that of haloperidol and the opiate peptide beta-endorphin. On the other hand, a time-course of plasma alpha-MSH levels after DE gamma E administration resembled the one which has been seen after haloperidol injection. From experiments performed on pituitary neurointermediate lobes incubated in vitro, it seems not likely that DE gamma E acts directly on the dopamine receptors of the pituitary in affecting alpha-MSH release. In conclusion, it appears that DE gamma E affects alpha-MSH levels in plasma in a way distinct from that of the neuroleptic drug haloperidol and of the opiate-peptide beta-endorphin.

Animals↗

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↗

Neurotensin and bombesin, a relationship between their effects on body temperature and locomotor activity?

Neurotensin and bombesin have been tested for their effects on body temperature and locomotor activity in an open field. Both peptides induce hypothermia and suppress ambulation and rearing. The time curves of the hypothermic effects of both peptides appear to be rather similar, although bombesin is a more potent hypothermic agent than neurotensin. The time curves of the effects on locomotor activity appear to be quite different. The suppressive effect of neurotensin on locomotor activity is relatively short lasting and reaches its maximum at approximately 32 minutes. The effect of bombesin follows a different time curve and shows two peaks, suggesting that two different mechanisms are involved in the suppressive action of bombesin on locomotor activity. Calculation of the correlation coefficients between the effects of neurotensin and of bombesin on body temperature and on locomotor activity (ambulation) suggest that a causal relationship between these two effects is not likely, in particular for neurotensin.

Animals↗