pituitrin and Memory-Disorders

1. Beyond its antidiuretic and vasopressor effects, vasopressin has central nervous system effects, first described in rats by David de Wied in 1965. 2. Its first clinical use in humans, in 1978, confirmed its stimulant action in normal individuals, especially in middle-aged male subjects. 3. Its utility in mnemic problems is also worht considering when the pathology is relatively recent (less than 2 years prior) and unaccompanied by major neurological lesions. Behavioral modifications, such as improvement of "sociability", "mood" improvement, independent of its effects on memory have been described, and would justify complementary clinical investigation. 4. New synthetic vasopressin derivatives which would eliminate metabolic effects while maintaining behavioral effects intact, and the definition of clinical, neuroendocrine, and neurophysiological prognostic criteria, will be the two most important paths for investigation over the next years.

Topics: Cognition; Humans; Memory Disorders; Pituitary Hormones, Posterior; Vasopressins

The neuropeptides vasopressin, adrenocorticotropin (ACTH), and beta-endorphin seem to have important effects on memory and learning. Animal studies attempting to demonstrate these effects are difficult to interpret because of the complexity of behavior that is described as "learning" and the impossibility of assessing verbal learning in animals. This article therefore reviews some of the animal literature on neuropeptides and learning, but focuses primarily upon studies in humans, both in normal volunteers and in patients with neurological disorders. Vasopressin enhances learning under some conditions. Intranasal administration has been associated with improvement on psychometric tests in patients with mild Alzheimer's disease and Korsakoff's psychosis, although these findings are not uniform. It improves performance on memory tests in normal volunteers, but does not seem to improve the memory deficit after head trauma. Cerebrospinal fluid levels are low in patients with Alzheimer's disease. ACTH and melanocyte-stimulating hormone (MSH) are two peptides the primary behavioral effect of which seems to be on attention or goal-motivated behavior rather than on memory processes themselves. Visual discrimination and the ability to continue repetitive tasks are enhanced; in mentally retarded subjects, the administration of ACTH or MSH improves performance on a variety of neuropsychological tests. It does not, however, improve cognitive function in the elderly. Endogenous opioids including beta-endorphin and met-enkephalin seem to have primarily an amnesic effect in animal studies. Their role in human learning is still uncertain, although naloxone, which antagonizes their effects, has been associated with improved cognitive performance in patients with Alzheimer's disease. These data underscore the complexity of the processes associated with human memory and the rudimentary state of our present knowledge. Whatever the mechanisms, however, vasopressin, ACTH, and endogenous opioids seem to have important effects upon memory.

Topics: Adrenocorticotropic Hormone; Animals; Endorphins; Forecasting; Humans; Learning; Melanocyte-Stimulating Hormones; Memory; Memory Disorders; Nerve Tissue Proteins; Nervous System Diseases; Oxytocin; Pituitary Gland, Posterior; Vasopressins

This review critically evaluates the animal and human research concerning vasopressin's putative mnemonic role. Weaknesses in the interpretations of the early animal experiments as well as the implications of the later inconsistent findings are discussed. It is concluded that both the initial enthusiasm and the subsequent skepticism concerning this hypothesized role were premature. This conclusion applies equally to the human research. A review of these studies reveals that almost all of the negative reports involved cognitively-impaired individuals. The relatively few studies that have been conducted concerning vasopressin's effects in unimpaired human subjects are consistent with the hypothesis that vasopressin does affect cognition, though both the mechanism of action and the specific cognitive processes which are altered have yet to be elucidated.

Topics: Animals; Arginine Vasopressin; Arousal; Avoidance Learning; Blood-Brain Barrier; Deamino Arginine Vasopressin; Extinction, Psychological; Haplorhini; Humans; Lypressin; Memory; Memory Disorders; Mice; Rats; Rats, Brattleboro; Vasopressins

No class of presently available drugs is able to alleviate the cognitive deficits which accompany senile dementia. The present article critically reviews the strategies which have until now been used to treat these deficits. A description is given of the cognitive deficits which are commonly seen and of the cerebral substrate underlying memory processes. Furthermore, the various treatment strategies are critically reviewed as well as the rationale behind the use of the currently available drugs. It is concluded that no clinically significant improvement of cognitive disturbances can be obtained with the present available drugs. The neuropeptide strategy however may reveal new pharmacotherapeutic possibilities in the near future.

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Anticonvulsants; Brain; Catecholamines; Choline; Dementia; Dihydroergotoxine; Humans; Memory Disorders; Narcotic Antagonists; Nerve Tissue Proteins; Neuropsychology; Parasympatholytics; Phosphatidylcholines; Physostigmine; Piracetam; Trace Elements; Vasopressins; Vitamins

Topics: Animals; Avoidance Learning; Conditioning, Classical; Deamino Arginine Vasopressin; Extinction, Psychological; Humans; Hypophysectomy; Injections, Intraventricular; Memory; Memory Disorders; Mice; Oxytocin; Pituitary Hormones; Pituitary Hormones, Posterior; Rats; Rats, Brattleboro; Retention, Psychology; Vasopressins

Topics: Administration, Intranasal; Adolescent; Adult; Craniocerebral Trauma; Female; Humans; Injury Severity Score; Lypressin; Male; Memory Disorders; Middle Aged; Neuropsychological Tests; Pilot Projects; Retrospective Studies; Vasopressins

In animals, evidence has been accumulated that vasopressin (VP) improves learning and memory. In humans, this effect was not consistently demonstrated, and attempts to restore age-related memory deficits by VP also remained inconsistent. Assuming that in old subjects a beneficial effect on memory occurs only after prolonged treatment with VP, we conducted a study in 26 healthy elderly persons receiving 40 IU of VP for three months through the intranasal route. The trial was randomized, placebo-controlled and held double-blind. Memory was assessed by the Auditory Verbal Learning Test (AVLT) requiring the subject to learn repeatedly presented lists of 15 words. Results demonstrated no general effect of long-term treatment with VP on memory in aged humans. However, recall of an interfering word list was improved, indicating a diminished proactive interference by the peptide. Additionally, VP influenced recall depending on the serial position of an item: it improved the primacy effect (i.e. recall of the first words of a list) and impaired the recency effect. This result may indicate an improved semantic encoding (i.e. a primary effect on processes of attention) after long-term administration of VP.

Topics: Administration, Intranasal; Aged; Aged, 80 and over; Double-Blind Method; Female; Humans; Male; Memory; Memory Disorders; Mental Recall; Neuropsychological Tests; Vasopressins; Verbal Learning

In a double-blind cross-over trial the memory effect of the neuropeptide desglycinamide arginine vasopressin (DGAVP) was selected because of its well-documented facilitatory effects on memory components in rodents. Patients with stabilized or progressive amnesic disorders (Korsakoff disease, early stages of Alzheimer dementia, head injuries and other central nervous system diseases) did not respond to the drug. Factors possibly explaining the discrepancy with animal research are discussed.

Topics: Adult; Aged; Amnesia; Arginine Vasopressin; Clinical Trials as Topic; Cognition; Double-Blind Method; Female; Humans; Intelligence Tests; Learning; Male; Memory; Memory Disorders; Middle Aged; Oxytocin; Random Allocation; Vasopressins

A vasopressin derivative or placebo was administered to 21 chronic schizophrenia patients for 3 weeks in a randomized crossover double-blind design. The patients were divided into those above and below the median on baseline memory measured by the Wechsler memory scale. Vasopressin treatment did not improve memory either in those patients with below median baseline memory or in the group as a whole.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Memory Disorders; Middle Aged; Random Allocation; Schizophrenia; Vasopressins

Topics: Alzheimer Disease; Amino Acid Sequence; Brain Injuries; Clinical Trials as Topic; Dementia; Humans; Memory; Memory Disorders; Middle Aged; Structure-Activity Relationship; Vasopressins

Topics: Aged; Animals; Choline; Clinical Trials as Topic; Humans; Male; Memory; Memory Disorders; Memory, Short-Term; Middle Aged; Rats; Vasopressins

Recently, chronic hyponatremia, even mild, has shown to be associated with poor quality of life and high mortality. The mechanism by which hyponatremia contributes to those symptoms, however, remains to be elucidated. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a primary cause of hyponatremia. Appropriate animal models are crucial for investigating the pathophysiology of SIADH. A rat model of SIADH has been generally used and mouse models have been rarely used. In this study, we developed a mouse model of chronic SIADH in which stable and sustained hyponatremia occurred after 3-week continuous infusion of the vasopressin V2 receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) and liquid diet feeding to produce chronic water loading. Weight gain in chronic SIADH mice at week 2 and 3 after starting dDAVP injection was similar to that of control mice, suggesting that the animals adapted to chronic hyponatremia and grew up normally. AQP2 expression in the kidney, which reflects the renal action of vasopressin, was decreased in dDAVP-infused water-loaded mice as compared with control mice that received the same dDAVP infusion but were fed pelleted chow. These results suggest that "vasopressin escape" occurred, which is an important process for limiting potentially fatal severe hyponatremia. Behavioral analyses using the contextual and cued fear conditioning test and T-maze test demonstrated cognitive impairment, especially working memory impairment, in chronic SIADH mice, which was partially restored after correcting hyponatremia. Our results suggest that vasopressin escape occurred in chronic SIADH mice and that chronic hyponatremia contributed to their memory impairment.

Topics: Animals; Behavior, Animal; Chronic Disease; Disease Models, Animal; Hyponatremia; Inappropriate ADH Syndrome; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Vasopressins

NC-1900, an arginine-vasopressin derivative, has been reported to enhance memory for avoidance behavior. Specifically, NC-1900 ameliorated cycloheximide-induced learning impairments in a passive avoidance test in rats. In the present study, we investigated that effects of NC-1900 on place learning in rats with selective lesions in the CA1 subfield of the hippocampal formation produced by transient forebrain ischemia. NC-1900 was administered daily (1 microg/kg, p.o.) 1 h before the place learning task. A rat was required to alternate between 2 small circular areas located diametrically opposite each other on the circumference of an open field in order to obtain intracranial electrical stimulation reward (the spatial navigation task). Rats with hippocampal lesions showed severe place learning impairments both in task performance (indicated by number of rewards obtained per a session) and in navigation performance (forming efficient trails) over the 30-day test period. Treatment with NC-1900 ameliorated deficits in the place learning exhibited by rats with the same hippocampal lesions, such that their performance reached normal levels. There were no significant differences in the ischemic hippocampal lesions, spontaneous locomotor activity, and stimulation current intensity between the treated and untreated rats. The results demonstrated that NC-1900 reduced place learning impairments produced by hippocampal lesions.

Topics: Amnesia; Animals; Brain Ischemia; Disease Models, Animal; Hippocampus; Learning; Male; Memory Disorders; Oligopeptides; Prosencephalon; Pyrrolidonecarboxylic Acid; Rats; Rats, Wistar; Vasopressins

The effects of [Arg(8)] vasopressin on histamine H(1) receptor antagonist-induced memory deficits were investigated using the eight-arm radial maze performance test in rats. Pyrilamine and diphenhydramine as well as scopolamine induced memory deficits characterized by increases in the number of total errors, reference memory errors and working memory errors. [Arg(8)] vasopressin improved not only scopolamine--but also pyrilamine--and diphenhydramine-induced memory deficits, although a high dose of [Arg(8)] vasopressin was needed to antagonize pyrilamine-induced memory deficits. The effects of pyrilamine on the brain [Arg(8)] vasopressin content were studied, and the hippocampus [Arg(8)] vasopressin content was shown to be decreased after pyrilamine injection. From these observations, it seems likely that [Arg(8)] vasopressin participates in not only the cholinergic system but also the histaminergic system in spatial memory.

Topics: Animals; Arginine Vasopressin; Brain; Diphenhydramine; Dose-Response Relationship, Drug; Histamine H1 Antagonists; Male; Maze Learning; Memory Disorders; Pyrilamine; Rats; Rats, Wistar; Scopolamine; Vasopressins

Topics: Brain Injuries; Female; Humans; Learning Disabilities; Male; Memory Disorders; Thermosensing; Vasopressins

Topics: Aged; Aging; Amnesia; Animals; Choline; Cholinergic Fibers; Female; Haplorhini; Humans; Male; Memory; Memory Disorders; Middle Aged; Psychological Tests; Rats; Vasopressins

Results of using vasopressin and pituitrin in 20 patients with memory disturbances of various genesis (due to circulatory disturbances in the vertebrobasilar system, cerebral atherosclerosis, neurasthenia, brain concussion, epilepsy) are reviewed. The therapeutic efficacy of the hormones was evaluated with the use of a complex of psychophysiological methods. Objective changes in the patients' neurological status and subjective state were taken into account. A high therapeutic efficacy of the hormones in the treatment of amnestic syndromes is demonstrated.

Topics: Adult; Amnesia, Retrograde; Basilar Artery; Brain Concussion; Brain Ischemia; Epilepsy, Temporal Lobe; Female; Humans; Intracranial Arteriosclerosis; Male; Memory Disorders; Middle Aged; Neurasthenia; Pituitary Hormones, Posterior; Vasopressins; Vertebral Artery

Topics: Aged; Humans; Lypressin; Male; Memory Disorders; Vasopressins