oxytocin and Amnesia

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

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

The neuropeptide oxytocin is essential for mammalian parturition and lactation. Recent animal studies suggest that oxytocin is also implicated in the central nervous control of behavior including learning and memory. There has been little investigation, however, of the impact of oxytocin on human memory. The purpose of this study was to investigate the effect of a single dose of intranasal oxytocin on implicit and explicit memory in humans. In a placebo-controlled, double-blind study, 38 healthy men were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before the study phase (incidental learning). Memory was measured using three different memory tests: an implicit perceptual test (word stem completion), an implicit conceptual test (category-cued semantic association), and an explicit test (cued recall). Due to the reproductive-biological role of oxytocin and the impact of adequate environmental conditions for the stimulation of behavioral effects of oxytocin known from animal research, we used semantic word stimuli with reproduction-related vs. neutral meaning. Oxytocin significantly impaired recall performance as compared with placebo treatment irrespective of the meaning of words in the cued recall test. In the implicit conceptual test, characterized by a deepened information processing, compared with placebo, oxytocin significantly impaired only the overall generation of associated target words with reproduction relevant meaning, whereas no significant difference between oxytocin and placebo was obtained for neutral words. These findings concur with data from animal research suggesting that central oxytocin selectively influences memory performance depending on the kind of memory test used and, more importantly, the psychobiological relevance of stimuli.

Topics: Administration, Intranasal; Adult; Amnesia; Cues; Double-Blind Method; Environment; Humans; Male; Memory; Mental Recall; Oxytocin; Perception; Psychometrics; Psychomotor Performance; Reading; Reproduction

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

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

Antiamnestic properties of memory neuropeptide--modulators and their effect on learning were studied as well as consolidation of oligopeptide ACTH4-7, vasopressin, oxytocin, leu enkephalin and the melanocyte inhibiting factor. Effect of these neuropeptides on the rat higher nervous activity is bath strong and specific: ACTH4-7 and leu enkephalin speed up the primary learning whereas vasopressin and oxytocin improve long--term memory. Peptides are able to reverse retrograde as well as anterograde amnesia and to preserve previously formed habits from disturbance by electric shock. Vasopressin and the melanocyte inhibiting factor are the strongest antiamnestic factors.

Topics: Adrenocorticotropic Hormone; Amnesia; Animals; Arginine Vasopressin; Conditioning, Classical; Electroshock; Enkephalin, Leucine; Escape Reaction; Humans; Male; Memory; Neurotransmitter Agents; Oxytocin; Peptide Fragments; Rats

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