Vasopressin analog (DDAVP) improves memory in human males

One specific analog of arginine vasopression, 1-desamine-8-D-arginine vasopressin (DDAVP), has been shown to improve learning and memory in humans. Healthy young male adult subjects treated with DDAVP demonstrated better memory for implicational sentences than did control subjects. The same treatment had no influence on women given the same memory task. These results suggest that DDAVP may have a sexually dimorphic effect on learning and memory.     

Vasopressin analog (DDAVP) facilitates concept learning in human males

The effects of desmopressin acetate (DDAVP) were studied in normal males. Subjects were given 60μg of DDAVP, a placebo, or no treatment and were given several behavioral tests. DDAVP enhanced learning of all problems on a concept shift task but had no effect on visual memory, anxiety, blood pressure or heart rate. It was suggested that DDAVP may influence memory via its actions on attention.     

Sentence memory affected by vasopressin analog (DDAVP) in cross-over experiment

DDAVP has been shown to facilitate memory, especially retrieval, in humans. Healthy young male adult subjects received DDAVP (60 micrograms) in a cross-over design with a one-week interval between sessions. Results indicated that DDAVP improved immediate memory during the first but not the second testing session, particularly for low-verbal subjects. Treatment with DDAVP also facilitated delayed (one-week) recall in the opposite group, a cross-over interaction that suggests a retrieval locus for the DDAVP effect. Furthermore, since DDAVP improved immediate memory more for low-verbal subjects and delayed memory more for high-verbal subjects, it appears that individual difference factors will be important in understanding the effects of vasopressin on memory.     

Failure of posttrial administration of vasopressin analogue (DDAVP) to influence memory in healthy, young, male volunteers

The effects of intranasal treatment with DDAVP on healthy, male volunteers was assessed. Subjects were asked to learn prose passages and then were given either 60 μg of DDAVP or saline in a double-blind procedure. Subjects were then asked to recall the passages after a 24-h delay. Treatment had no effect on recall of passages. This suggests that treatment with vasopressin affects acquisition rather than consolidation of newly learned information.     

Vasopressin potentiates the stimulation of cyclic AMP accumulation by norepinephrine

Vasopressin, a peptide that appears to enhance the consolidation process of memory was studied for its ability to stimulate the accumulation of cyclic AMP in slices of the mouse hippocampus. While vasopressin alone exhibited no effects in this system, it substantially potentiated the effects of norepinephrine. Such actions are discussed in reference to an endogenous brain vasopressin system, and they suggest a possible neuromodulator role for vasopressin.     

Vasopressin and vasotocin facilitate reversal of a brightness discrimination

Male albino rats received vasopressin, vasotocin, pressinoic acid or placebo and were tested on an aversively motivated brightness discrimination task. Treatment with both vasopressin and vasotocin had no effect on acquisition but facilitated the reversal of the discrimination. Pressinoic acid had an inconsistent effect. The results are interpreted to show that the C terminal of the peptides vasopressin and vasotocin influence potency of these peptides. Furthermore, the results are interpreted as showing that both vasotocin and vasopressin influence selective attention during aversively motivated tasks.     

Vasopressin analog delays extinction of classically conditioned bradycardia

Albino rabbits were subjected to Pavlovian (classical) conditioning and extinction of concomitant heart rate and eyeblink responses. Sixty minutes before each of three extinction sessions animals were treated with 5 or 20 μg/kg of deamino-dicarba-arginine-8-vasopressin or saline. Vasopressin treatment delayed extinction of bradycardiac conditioned responses but did not affect concomitant eyeblink conditioned responses. It was concluded that classically conditioned autonomic responses may be useful tools for studying the effects of peptides on learning.     

MSH/ACTH4-10: a tool to differentiate between the role of vasopressin in memory consolidation or retrieval processes

MSH/ACTH4-10 induces a dose dependent increase of latency scores during retention of a passive avoidance response, when injected SC prior to retention but not when administered immediately after the learning trial. Intracerebroventricular administration of anti-vasopressin serum immediately after the learning trial or 1 hr prior to retention induces marked deficits in passive avoidance behavior as indicated by low latencies during retention. SC injection of MSH/ACTH4-10 increased latency scores in animals which received anti-vasopressin serum prior to retention, but did not alter latencies in animals, which received anti-vasopressin serum after the learning trial. These results suggest that MSH/ACTH4-10 is involved in retrieval processes and is able to differentiate between the effects of vasopressin on memory consolidation and on retrieval.     

Effects of DDAVP on gender-specific verbal and visuospatial tasks in healthy young adults

Although several studies have demonstrated the efficacy of the vasopressin analog DDAVP in enhancing human cognition, few previous studies have explored possible interactions of treatment with DDAVP and gender in healthy young adults. The present study was undertaken to explore the effects of treatment with DDAVP on gender-specific tasks. Male and female volunteers were treated with either DDAVP or saline and asked to recall lists of words and to perform the Paper Folding and Stroop Color Word Tests. Although treatment with DDAVP produced few effects in these tasks, the effects that were noted involved impairment of performance.     

Effects of retention interval on performance in a numerical reproduction task

The retention interval (RI) between the sample and production phase in a numerical reproduction task was varied to determine whether a "produce-small" effect would be obtained with increased delays. Four pigeons were trained with a retention interval of 2s, and then tested with intervals of 0.5s and 8s. Results showed a number-dependent, "produce-large" effect-response number increased when RI was increased-analyses of average response number and accuracy suggested RI affected responding most on the 2-flash trials with an 8-s RI. Additionally, discrimination between trial types decreased as RI increased. Existing explanations for the "choose-short/small" effect appear unable to account for these results; however the "produce-large" effect may be attributed to a disruption in stimulus control over responding.     

Quantitation of Vasopressin mRNA and Oxytocin mRNA in Hypothalamic Nuclei by Solution Hybridization Assays

Concentrations of vasopressin (VP) precursor and oxytocin (OT) precursor mRNA were measured in magnocellular cell groups of the rat hypothalamus by newly developed solution hybridization assays. The assays employed single-stranded 35S-labeled VP-specific and OT-specific DNA probes that were prepared by primer extension on recombinant M13 DNA templates. Solution hybridization assays were standardized by known amounts of cloned DNA. The detection limit was less than 1 pg DNA equivalent of the respective mRNA. In total RNA preparations of microdissected supraoptic nucleus (SON) mean (+/- SEM) basal levels of 1.37 +/- 0.18 pg VP mRNA and 1.95 +/- 0.14 pg OT mRNA were measured. RNA of the microdissected paraventricular nucleus (PVN) contained 0.35 +/- 0.02 pg VP mRNA and 1.77 +/- 0.15 pg OT mRNA. Elevation of plasma osmolality induced by drinking of 2% saline for 25 days resulted in a 1.85-fold increase in VP mRNA levels of the SON and a 1.6-fold increase in VP mRNA levels of the PVN. The solution hybridization assays are suitable tools to study the regulation of VP and OT mRNAs in magnocellular neurons of the brain.     

Immunocytochemical evidence for the presence of oxytocin and neurophysin in the large cells of the bovine corpus luteum

Summary The presence of neurophysin, oxytocin and vasopressin in the bovine corpus luteum was examined immunocytochemically. Tissue blocks of corpora lutea from pregnant and non-pregnant animals were fixed with glutaraldehyde/paraformaldehyde fixative and immunostained by the peroxidase-antiperoxidase (PAP) method. The simultaneous presence of immunoreactive oxytocin and immunoreactive oxytocin-neurophysin was demonstrated in large luteal cells of non-pregnant animals, while no staining for vasopressin or vasopressin-neurophysin was observed. None of the peptides were detected in the corpus luteum of pregnant animals. The small luteal cells were not found to be stainable at any time.     

Immuno-electron microscopical demonstration of vasopressin and oxytocin synapses in the limbic system of the rat

Summary The extensive distribution of exohypothalamic vasopressin or oxytocin containing nerve fibres is thought to be the anatomical basis for the involvement of these neuropeptides in central processes. Following light microscopic observations suggesting that these fibres terminate on other neurons, the present study was undertaken to demonstrate the existence of such endings in the limbic system, which is one of the main target areas for these peptides. For immunoelectron microscopy glutaraldehyde-paraformaldehyde perfused brains of male Wistar rats and Brattleboro rats, homozygous for diabetes insipidus, with and without postfixation in OsO₄, were used. Post-embedding staining revealed false positive reaction product on all dense core vesicles, e.g., in the lateral septum. With pre-embedding staining, however, intense and specific reactions were observed for both vasopressin and oxytocin at their sites of production, as well as the neurohypophysis and in the extrahypothalamic limbic brain regions.In the lateral septum and habenular nucleus only vasopressin-containing synapses could be demonstrated, while in the medial nucleus of the amygdala synapses containing either vasopressin or oxytocin were observed. These peptide containing synapses do not seem to differ in any fundamental way from the classical transmitter-containing synapses in the brain.Supported by the Foundation for Medical Research FUNGOThe authors wish to thank Prof. Dr. A.H.M. Lohman for having made the vibratome available, and Miss C. de Raay for her expert technical assistance     

Testosterone modulates performance on a spatial working memory task in male rats

Gonadal hormones have been shown to modulate memory retention in female rats. The current experiments examine the role of testicular hormones in modulating the performance of male rats on two spatial water maze tasks. In the first study, castrated and intact rats were trained on the visible platform and hidden platform versions of the Morris water maze task. Castration did not affect performance on either version of this reference memory task with castrated and intact rats demonstrating similar performance both during acquisition and on post-training probe trials. In the second experiment, castrated and intact rats were tested on a delayed-matching-to-place version of the water maze. Rats received a series of trial pairs in the maze with a hidden platform located in the same pool location on the exposure and retention trials of each pair; between pairs of trials, however, the platform was repositioned to a novel pool location. The interval between trials was either 10- or 60-min and memory retention, taken as the difference between the pathlengths on the exposure and retention trials, declined as the interval increased. Relative to intact males, castrated males demonstrated impaired working memory retention at 60-min but not at 10-min retention intervals. This interval-dependent impairment in working memory retention was reversed by physiologic levels of testosterone replacement. These findings indicate that castration does not significantly affect acquisition or probe trial performance on a classic reference memory task but does impair spatial working memory retention, an effect that is reversed by exogenous testosterone.     

Vasopressin Antagonist Disrupts the Circadian Rhythm of Water Intake on Suprachiasmatic Injection

The present study makes an attempt to find out the action of arginine vasopressin (AVP) and its antagonist d-(CH₂)₅Tyr (Me) AVP applied at the suprachiasmatic nuclei (SCN) on the circadian rhythm of water intake. Chronic implantation of a 22 G stainless steel cannula for injection was performed using a stereotaxic technique under Nembutal anesthesia. AVP and its antagonist were injected into the SCN of free-moving rats at the beginning of light and dark phases of the light-dark (LD) cycle. Injections of AVP during either phase did not disrupt the circadian pattern of water intake while the injections of the antagonist disrupted it. The findings are suggestive of the involvement of AVP as a mediator of the circadian rhythm of water intake at the level of the neural pacemaker, SCN.     

Vasopressin Antagonist Disrupts the Circadian Rhythm of Water Intake on Suprachiasmatic Injection

The present study makes an attempt to find out the action of arginine vasopressin (AVP) and its antagonist d-(CH₂)₅Tyr (Me) AVP applied at the suprachiasmatic nuclei (SCN) on the circadian rhythm of water intake. Chronic implantation of a 22 G stainless steel cannula for injection was performed using a stereotaxic technique under Nembutal anesthesia. AVP and its antagonist were injected into the SCN of free-moving rats at the beginning of light and dark phases of the light-dark (LD) cycle. Injections of AVP during either phase did not disrupt the circadian pattern of water intake while the injections of the antagonist disrupted it. The findings are suggestive of the involvement of AVP as a mediator of the circadian rhythm of water intake at the level of the neural pacemaker, SCN.     

Immunocytochemical evidence for the presence of oxytocin in rat testis

Summary The presence of oxytocin, vasopressin and neurophysin in the testis of adult Wistar and Brattleboro rats has been examined immunocytochemically. After fixation in modified Bouin's solution, or Bouin's sublimate fixative, immunostaining was accomplished with the peroxidase-antiperoxidase method. The presence of immunoreactive oxytocin was demonstrated in 80% of the interstitial cell population of both rat strains while no staining was observed for vasopressin or neurophysin.     

The effect of ostensive cues on dogs’ performance in a manipulative social learning task

In contrast to animal social learning (e.g. dogs learning from observing another dog), humans typically teach by attracting the attention of the learner. Also during the training of dogs, humans tend to attract their attention in a similar way. Here, we investigated dogs’ ability to learn both from a dog and a human demonstrator in a manipulative task, where the models demonstrated which part of a box to manipulate in order to get a food reward. We varied the communicative context both during the dog and during the human demonstration comparably: a second experimenter directed the attention of the subjects to the model (dog/human ostensive demonstration) or remained silent (dog/human non-ostensive demonstration). Moreover, we investigated whether the training level of the dogs (well-trained vs. untrained) affected how the dogs performed in the manipulative tasks after the different demonstrations.We found that better trained dogs showed significantly better problem solving abilities. They paid more attention to the human demonstration than to the dog model, whereas such a difference in attentiveness of the less trained dogs was not found. Despite slight differences in paying attention to the different demonstrators, the presence of human or the dog demonstrators exerted equally effectiveness on the test performance of the dogs. However, the effectiveness of the demonstrations was significantly reduced if ostensive cues were given during the demonstrations by a second experimenter. Analysis of attentiveness and activity of the observer dogs during the demonstrations indicates that the reason for this negative effect was a combination of distracted attention paid to the demonstration and a higher level of excitement in the ostensive than in the non-ostensive demonstrations.This study suggests that third party communication during demonstration attracts dogs’ attention to the communicator instead of paying close attention to the model. We suggest that precise timing and synchronization of attention-calling and demonstration is necessary to avoid this distracting effect.     

Effect of Tetanus Toxin on Oxytocin and Vasopressin Release from Nerve Endings of the Neurohypophysis

The effect of tetanus toxin on neuropeptide hormone release from isolated nerve endings of the neural lobe of rat pituitaries (neurosecretosomes) was measured in a perfusion system. Tetanus toxin inhibited depolarization-evoked release of oxytocin and vasopressin in a time- and dose-dependent manner. At 1 microgram/ml, tetanus toxin blocked stimulated release by 85%. Tetanus toxin that was preincubated with a neutralizing monoclonal antibody or heated to 100 degrees C had no effect on hormone release. The ionophores A23187 and ionomycin were potent stimulators of hormone release in control nerve endings, but were not able to overcome the effect of tetanus toxin in intoxicated nerve endings. 8-Bromo-cyclic GMP, which has been reported to reverse the action of tetanus toxin in PC12 cells, had no effect on the action of tetanus toxin in neurosecretosomes. Neurosecretosomes are the first system in which tetanus toxin has been shown to block release from peptidergic nerve terminals. They appear to be a valuable in vitro system for studying the biochemical mechanism of tetanus toxin action.     

Vasopressin affects the behavior of rats in a positively-rewarded discrimination task

The effects of subcutaneous injections of vasopressin were investigated in a study utilizing 72 male Long-Evans rats trained in an appetitive black-white discrimination T-maze task. Animals which were reinforced for choosing the black goal arm demonstrated prolonged extinction if they received vasopressin prior to daily extinction sessions. This effect was not observed in animals reinforced for choosing the white goal arm. Prolonged extinction was not found in animals which received vasopresson only during acquisition or in control animals which received saline. Speed and activity scores did not differentiate the groups. These results demonstrate that vasopressin can affect the behavior of rats on a positively-reinforced task.