pituitrin and Amnesia

Topics: Amnesia; Animals; Avoidance Learning; Humans; Learning; Memory; Oxytocin; Vasopressins

Topics: Adrenal Medulla; Amnesia; Amygdala; Animals; Avoidance Learning; Epinephrine; Hormones; Learning; Memory; Pituitary Hormones, Posterior; Rats; Rats, Brattleboro; Vasopressins

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)

Topics: Amnesia; Animals; Brain; Humans; Memory; Mental Disorders; Nerve Tissue Proteins; Psychological Tests; Vasopressins

Topics: Amnesia; Animals; Behavior, Animal; Brain; Drug Interactions; Electrophysiology; Humans; Memory; Neurons; Neurotransmitter Agents; Oxytocin; Vasopressins

Topics: Adrenocorticotropic Hormone; alpha-Methyltyrosine; Amnesia; Amphetamine; Animals; Anisomycin; Cycloheximide; Disease Models, Animal; Electroshock; Ether; Ethyl Ethers; Humans; Learning; Methyltyrosines; Phenoxybenzamine; Protein Biosynthesis; Puromycin; Reserpine; Strychnine; Tyrosine 3-Monooxygenase; Vasopressins

Topics: Adrenocorticotropic Hormone; Aged; Amnesia; Brain; Contingent Negative Variation; Cyclic AMP; Electroencephalography; Humans; Male; Memory; Mental Disorders; Middle Aged; Myelin Sheath; Neurotransmitter Agents; Phosphorylation; Pituitary Hormones; Prostaglandins; Schizophrenia; Vasopressins

The neurohypophyseal hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates, while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophyseal hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation; the linear parts, retrieval processes; while nearly the whole oxytocin or vasotocin molecule is needed for attenuation of consolidation and retrieval. Regional studies, utilizing microdissection techniques in combination with a sensitive radioenzymatic catecholamine assay, revealed a distinct pattern of effects on cerebral alpha-methyl-p-tyrosine methylester-induced catecholamine disappearance following intraventricular vasopressin administration in limbic midbrain structures. In situations in which the amount of bioavailable vasopressin in the brain is absent, as is the case in the Brattleboro rat with hereditary diabetes insipidus, or neutralized in normal Wistar rats following the intraventricular administration of antivasopressin serum, regional catecholamine disappearance in most cases is altered in a direction opposite to that observed after intracerebroventricular vasopressin administration. These results indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle.

Topics: Amnesia; Animals; Biological Availability; Brain; Catecholamines; Chemical Phenomena; Chemistry; Drug Tolerance; Heroin Dependence; Humans; Melanocyte-Stimulating Hormones; Memory; Morphine Dependence; Oxytocin; Pituitary Gland, Posterior; Rats; Vasopressins

Pituitary hormones profoundly influence behavior through direct actions on the brain. One of these behavioral effects is the attenuation of experimental amnesia. Traditionally, amnesia is considered as a "loss of memory." Memory comprises at least 2 stages: input (memory consolidation) and output (memory retrieval). Theoretically, disturbance of either aspect of memory may be the cause of amnesia. Also, it is possible that amnesia is based on a factor or factors not related to memory. Data and theories on amnesia in man were reviewed. Some salient features were mentioned: (1) amnesia can be induced by a variety of agents; (2) amnesia covers periods ranging from seconds to years; (3) amnesia gradients can be established; (4) amnesia is to a large extent reversible. From this survey, it seems possible that amnesia is not a homogeneous phenomenon and that even in one person a disturbance of both memory consolidation and memory retrieval may be produced by one and the same event. Animal studies in general have confirmed these conclusions. We have developed an animal model in order to study the effects of pituitary peptides on amnesia. This model is based on CO2-induced amnesia for a one-trial passive avoidance response in rats. This amnesia could be attenuated by treatment with ACTH-analogs 1 hour before the retrieval test. This anti-amnesic effect of ACTH-analogs was not dependent on the nature of the behavioral response or the amnesic treatment. The vasopressin-analog DGLVP similarly exerted an anti-amnesic effect when injected before the retrieval trial. In contrast to ACTH-analogs, however, it also reduced the amnesia when injected before acquisition. These results suggest that amnesia may comprise a "faulty-consolidation" and a "faulty-retrieval" component, which may be amended by different pituitary hormones. The study of the anti-amnesic activity of peptides therefore not only serves to characterize the nature of the behavioral effect of these peptides but may also prove to be helpful of the unraveling of processes involved in amnesia.

Topics: Adrenocorticotropic Hormone; Amnesia; Animals; Carbon Dioxide; Humans; Memory; Peptides; Pituitary Hormones; Rats; Species Specificity; Structure-Activity Relationship; Vasopressins

Topics: Adrenocorticotropic Hormone; Aged; Aging; Amnesia; Animals; Avoidance Learning; Behavior, Animal; Cognition Disorders; Endorphins; Extinction, Psychological; Humans; Hypophysectomy; Male; Memory; Middle Aged; Peptides; Pituitary Hormones; Rats; Retention, Psychology; Vasopressins

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

Topics: Adult; Aged; Amnesia; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Memory; Middle Aged; Physostigmine; Vasopressins

Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which is essential for mutual recognition. When CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism spectrum disorders (ASDs), characterized by defects in reciprocal social interaction and communication, occur either sporadically or in a familial pattern. However, the etiology of ASDs remains largely unknown. Therefore, the theoretical basis for pharmacological treatments has not been established. Hence, there is a rationale for investigating single nucleotide polymorphisms (SNPs) in the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP rs3796863 (C>A) was associated with high-functioning autism (HFA) in American samples from the Autism Gene Resource Exchange. Although this finding was partially confirmed in low-functioning autism subjects in Israel, it has not been replicated in Japanese HFA subjects. The second SNP of interest, rs1800561 (4693C>T), leads to the substitution of an arginine (R) at codon 140 by tryptophan (W; R140W) in CD38. This mutation was found in four probands of ASD and in family members of three pedigrees with variable levels of ASD or ASD traits. The plasma levels of OXT in ASD subjects with the R140W allele were lower than those in ASD subjects lacking this allele. The OXT levels were unchanged in healthy subjects with or without this mutation. One proband with the R140W allele receiving intranasal OXT for approximately 3years showed improvement in areas of social approach, eye contact and communication behaviors, emotion, irritability, and aggression. Five other ASD subjects with mental deficits received nasal OXT for various periods; three subjects showed improved symptoms, while two showed little or no effect. These results suggest that SNPs in CD38 may be possible risk factors for ASD by abrogating OXT function and that some ASD subjects can be treated with OXT in preliminary clinical trials.

Topics: Administration, Intranasal; ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Amnesia; Animals; Autistic Disorder; Brain; Exons; Humans; Introns; Memory; Mice; Mice, Knockout; NAD; Oxytocin; Polymorphism, Single Nucleotide; Vasopressins

CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.

Topics: ADP-ribosyl Cyclase 1; Amnesia; Animals; Calcium; Calcium Signaling; Female; Gene Expression Regulation; Humans; Injections; Male; Maternal Behavior; Memory; Mice; Motor Activity; Oxytocin; Social Behavior; Vasopressins

In the present study, we investigated the facilitative effect of NC-1900, a new arginine vasopressin (AVP(1-9)) fragment analog, on memory performance in eight-arm radial maze or passive avoidance (PA) tasks in nonamnesic and amnesic (PA tasks only) mice. In the radial maze, all injections (subcutaneous) were given daily 60 min before each trail. NC-1900 (1 ng/kg)-treated animals showed enhancement of performance, and AVP(4-9) (1 microg/kg), an AVP(1-9) fragment, had similar effects, although the effective dose was 1000-fold higher. In the PA task, all drugs were administrated subcutaneously 60 min before the acquisition trial (Acq.), and the amnesic mice were exposed to CO(2) just after the Acq. NC-1900 (1 ng/kg) enhanced the memory performance of nonamnesic mice and ameliorated CO(2)-induced amnesia. AVP(4-9) (1 microg/kg) had a similar effect, although only at higher doses, while AVP(1-9) (0.1-1 microg/kg) had no effect. The facilitating effect of NC-1900 on nonamnesic mice was inhibited by coinjection [Pmp(1)-Tyr(Me)(2)]-AVP (Pmp,Tyr-AVP; 1 microg/kg), a V(1A) antagonist, but not by OPC-31260, a vasopressin(2) (V(2)) antagonist. The effect of NC-1900 on CO(2)-induced amnesia was also decreased by coinjection of Pmp,Tyr-AVP or [deamino-Pen(1), Me-Tyr(2)]-AVP (10 microg/kg), both of which are V(1) antagonists. These results suggested that NC-1900 has a more potent effect on facilitation of memory via the V(1A) receptor than AVP(4-9) in non- and CO(2)-amnesic conditions.

Topics: Amnesia; Animals; Carbon Dioxide; Male; Maze Learning; Memory; Mice; Oligopeptides; Peptide Fragments; Pyrrolidonecarboxylic Acid; 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 effect of neuropeptides and their analogs on anoxia-induced amnesia was examined using one-trial passive avoidance task in mice. Anoxia, produced by the exposure to CO2 immediately after the acquisition of avoidance response, induced amnesia which is shown by a short latency to enter from the safety compartment into the shocked compartment in the retention test conducted 24 hr later. In these anoxia-treated animals, thyrotropin-releasing hormone (TRH: 10-20 mg/kg), its analog DN-1417 (10-20 mg/kg) and ACTH 4-10 (66 micrograms/body), which were given sc 15-60 min before the retention test, markedly prolonged the latency in a dose-dependent manner, indicating a reversal of the amnesia. Arginine- and lysine-vasopressin also reversed the amnesia at a dose of 100 micrograms/body. These results suggest that TRH and DN-1417, known to reverse the amnesia produced by the protein synthesis inhibitor cycloheximide, have ameliorating effects on the retrieval process of memory.

Topics: Adrenocorticotropic Hormone; Amnesia; Animals; Hypoxia; Male; Memory; Mice; Thyrotropin-Releasing Hormone; Vasopressins

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

Topics: Adolescent; Amnesia; Encephalitis; Herpes Simplex; Humans; Male; Vasopressins

[Ile3, Arg8]vasopressin (arginine-vasotocin), as well as the C-terminal tripeptides of the neurohypophyseal hormones arginine and lysine vasopressin, Pro-Arg-Gly-NH2 and Pro-Lys-Gly-NH2, were protective against puromycin-induced amnesia in mice when administered 24h before training. The N-protected tripeptide derivative, Z-Pro-Lys-Gly-NH2, was effective when given 5 days before training. The effectiveness of all peptides to attenuate puromycin-induced amnesia decreased as the interval between training and peptide treatment increased, indicating that the peptides influence memory processes, rather than general arousal. Z-Pro-Lys-Gly-NH2 was active at 24h after training, when the other peptides were no longer effective. Although it seems clear that neurohypophyseal hormones per se can attenuate puromycin-induced amnesia, these results are in line with the possibility that some portion of hormone action may be mediated via formation of longer-lived hormone fragments in the CNS.

Topics: Amnesia; Animals; Arginine; Arginine Vasopressin; Humans; Hypothalamus; Memory; Mice; Neurophysins; Oligopeptides; Puromycin; Time Factors; Vasopressins

Topics: Administration, Intranasal; Adult; Amnesia; Amnesia, Retrograde; Female; Humans; Male; Middle Aged; Vasopressins

Topics: Administration, Intranasal; Alcohol Amnestic Disorder; Amnesia; Female; Humans; Male; Middle Aged; Vasopressins

Topics: Amnesia; Amnesia, Retrograde; Animals; Carbon Dioxide; Electroshock; Humans; Lypressin; Male; Memory; Pentylenetetrazole; Puromycin; Rats; Time Factors; Vasopressins

Lysine vasopressin (1 microgram/rat SC) administered 1 hr prior to either the acquisition trial or 24 hr retention trial facilitated passive avoidance retention. Amnesia was produced when a single 50 mg/kg (IP) injection of pentylenetetrazol was given immediately following the passive avoidance acquisition trial. A single injection of lysine vasopressin (1 microgram/rat SC) administered 1 hr prior to either the acquisition trial or 24 hr retention trial antagonized the amnesia.

Topics: Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; Humans; Lypressin; Male; Memory; Pentylenetetrazole; Rats; Seizures; Time Factors; Vasopressins

Topics: Adrenocorticotropic Hormone; Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; Carbon Dioxide; Humans; Lypressin; Male; Peptide Fragments; Rats; Time Factors; Vasopressins

Neurohypophyseal hormones and several of their analogs, as well as N-terminal and C-terminal fragments, have been studied for their ability to attenuate puromycin-induced amnesia in mice. [8-Lysine]vasopressin, [8-arginine]vasopressin, and the analogs des-9-glycinamide-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-lysine]vasopressin, [1,6-aminosuberic acid, 8-lysine]vasopressin, [4-leucine, 8-lysine]vasopressin, glycyl-glycyl-glycyl-[8-lysine]vasopressin, [1-beta-mercaptopropionic acid, 8-D-arginine]vasopressin, and [1,6-aminosuberic acid, 8-arginine]vasopressin are active. [8-Arginine]oxytocin as well as oxytocin and all of its other analogs tested are inactive with the striking exception of glycyl-glycyl-glycyl-oxytocin. The structural aspects of the neurohypophyseal hormones which appear to be important for significant activity in memory consolidation include the combination of a cyclic moiety containing the Tyr and Phe residues along with a basic residue in position 8. Another series of active compounds comprises C-terminal neurohypophyseal peptides and analogs thereof, including the naturally occurring Pro-Leu-Gly-NH2 and, most surprisingly, Leu-Gly-NH2, as well as its derivatives D-Leu-Gly-NH2 and the diketopiperazine, cyclo(-Leu-Gly-).

Topics: Amnesia; Animals; Brain; Humans; Memory; Mice; Oxytocin; Pituitary Hormones, Posterior; Puromycin; Structure-Activity Relationship; Vasopressins; Vasotocin

Topics: Adrenocorticotropic Hormone; Amnesia; Animals; Avoidance Learning; Carbon Dioxide; Electroshock; Humans; Male; Memory; Rats; Reaction Time; Vasopressins