Elsevier

Physiology & Behavior

Volume 83, Issue 1, 30 October 2004, Pages 31-38
Physiology & Behavior

Selective amnesic effects of oxytocin on human memory

https://doi.org/10.1016/j.physbeh.2004.07.020Get rights and content

Abstract

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.

Introduction

Four decades ago, David de Wied [1], one of the pioneers in behavioral neuroscience, showed that in the rat, the neuropeptide oxytocin plays a central role in behavioral regulation in general, and in learning and memory in particular. Subsequently, numerous studies went on to demonstrate that in addition to its most well-known peripheral role in parturition and lactation, oxytocin promotes positive social interaction (e.g., pair bonding, maternal behavior, sexual behavior, social attachment), inhibits stress-responsive neuroendocrine systems (e.g., hypothalamic–pituitary–adrenal axis), and modulates cognitive performance (e.g., learning, memory) [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14].

Oxytocin belongs to a family of nine-amino-acid peptides that have been identified in all classes of vertebrates and many invertebrate species [15]. Oxytocin and the closely related nonapeptide arginine-vasopressin are the only members of this family of peptides that are identified in mammals. Oxytocin is synthesized in magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus [16], [17]. The peptide is processed from its precursor form, together with the carrier protein, along the axonal projection to the posterior pituitary, from which it is secreted into the systemic circulation [18]. In addition, oxytocin is widely distributed throughout the central nervous system from smaller parvocellular neurons, influencing many neurobehavioral functions [10], [19], [20], [21]. Prominent oxytocin receptor binding has been found in various brain regions, in particular the hippocampus and the septum [19], [22], [23], [24], [25], [26], [27]. These findings suggest that the brain is a target organ for oxytocin and that this peptide may function as a neurotransmitter or neuromodulator in the central nervous system.

The neuropeptides oxytocin and arginine-vasopressin may have opposite roles, the former impairing memory and learning processes, and the latter improving cognitive performance [28], [29]. However, recent studies in animals suggest that oxytocin and vasopressin may be differentially involved in cognitive behavioral regulation depending on the behavioral test, the application or endogenous stimulation of the peptide, and the area of the brain under study [30]. Similar to the studies in animals, studies in healthy humans also showed inconsistent effects of oxytocin on memory function. Whereas some studies report impaired memory following oxytocin administration [31], [32], others were not able to confirm such memory effects [33], [34], [35].

Human memory has been subdivided into two categories, implicit and explicit [36]. Whereas explicit tests require subjects to retrieve previously studied items, implicit tests do not mention the study episode and measure retention indirectly as a facilitation of performance in a seemingly unrelated task. This facilitation is known as priming. Direct tests of memory, such as recall or recognition tasks, are used to measure explicit memory, while indirect tests of memory, such as word stem completion, are used to measure implicit memory. Implicit tests of memory can further be classified as perceptual or conceptual. While the cues in perceptual tests have a perceptual relation with their studied targets (e.g., din- for dinosaur within a word stem completion task), the cues in conceptual tests have a conceptual or semantic relation (e.g., reptiles within a category-cued association task). The distinction between implicit and explicit tests is supported by numerous findings of dissociations between performance under implicit and explicit conditions [36], [37]. For example, amnesic patients are severely impaired in explicit tests but not in most of the implicit measures of memory [38].

In the present study, we investigated the effects of oxytocin on implicit and explicit memory functions in healthy men. It should be noted within this context that neuropharmacological research has demonstrated that several pathways to the brain pass the blood–brain barrier, and there is convincing evidence that peptides gain access to the brain after intranasal administration in humans [6], [39], [40], [41], [42], [43]. In the present study, we therefore used double-blind, placebo-controlled intranasal administration of the neuropeptide to induce central nervous effects. Due to the reproductive role of oxytocin and the impact of adequate environmental conditions for the stimulation of behavioral effects of oxytocin, as known from animal research [12], [44], [45], [46], we used semantic word stimuli with and without reproduction-related meaning.

Section snippets

Subjects

A total of 38 healthy men (mean age=23.7 years, S.D.=3.0) were recruited by local advertisements for paid participation in the study. The study was conducted at the University of Trier, Germany. Before entering the study, all subjects underwent a standardized interview to screen out chronic diseases, mental disorders, medication, and drug or alcohol abuse. Subjects were instructed to abstain from food and drink (other than water) for 2 h before they reported to the laboratory, and from alcohol,

Description of subjects

As described in Methods, participants were randomly assigned to either the oxytocin or placebo group. Groups did not differ significantly in age and education. In addition, there were no significant differences between the two groups (mean±S.D.) with respect to anxiety (38.10±9.78 vs. 36.33±7.81; t(36)=−.61, p=.55) or depression (34.00±6.46 vs. 33.10±4.87; t(36)=−.48, p=.64). Trait anxiety (37.26±8.83) and depression scores (33.58±5.70) of all subjects were within the normal range of the

Discussion

The effects of intranasally administered oxytocin reported above suggest that central oxytocin in humans selectively influences memory performance depending on the kind of memory test and the psychobiological relevance of stimuli. There was a memory impairing effect on recall performance of studied words in the cued recall test in those who received oxytocin relative to the placebo group. However, the impaired cued recall performance was unrelated to the meaning of words, i.e., neutral and

Acknowledgments

The authors would like to thank Ines Simbrig, MS, and Sabine Wagner, MS, for research assistance. We thank Dr. Beate Ditzen and Ulrike Rimmele, MS, for helpful discussions and Anuschka Enzler and Sarah Mannion for editing assistance.

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