Psychoneuroendocrinology 1998 Nov;23(8):749-50  Introduction to
psychoneuroendocrinology volume: is there a neurobiology of love?
Uvnas-Moberg K, Carter CS
Department of Physiology, Karolinska Institute, Stockholm.
kerstin.uvnas-moberg@fyka.ki.se

Psychoneuroendocrinology 1998 Nov;23(8):751-64
The evolutionary antecedents to love.
Crews D Institute of Reproductive Biology, University of Texas at Austin
78712, USA. crews@mail.utexas.edu

Behaviors are adaptations to the physical, biotic, and social environments. Great diversity exists among vertebrates in reproductive behaviors and the neuroendocrine mechanisms underlying these behaviors. Study of this diversity illuminates species, population, and sex differences in hormone-brain-behavior relations. It also can provide insights into how and why certain neuroendocrine mechanisms evolved. Discoveries in evolution and ecology, neuroscience and endocrinology, are complementary and interrelated, and when applied in behavioral neuroscience, the investigator's perspective is less constrained by existing dogma. Naturally-occurring organisms not typically studied can be especially useful as their unusual adaptations illustrate alternative solutions to particular problems. Indeed, they 'often force one to abandon standard methods and standard points of view' with the result that, 'in trying to comprehend their special and often unusual adaptation, one often serendipitously stumbles on new insights' (Bartholomew, 1982). Thus, to ignore comparative research would greatly limit our understanding of the evolution of hormone-behavior relations. As Bullock (1984) admonishes, "without due consideration of the neural and behavioral correlates of differences between higher taxa and between closely related families, species, sexes, and stages, we cannot expect to understand our nervous systems or ourselves".

Psychoneuroendocrinology 1998 Nov;23(8):765-78
Generic aspects of primate attachments: parents, offspring and mates.
Mason WA, Mendoza SP Department of Psychology, University of California,
Davis 95616, USA. wamason@ucdavis.edu

We examine behavioral and physiological aspects of primate emotional attachments in the context of four relationships: infant-to-parent, parent-to-infant, and adult male-to-female and adult female-to-male in a monogamous New World species. Emotional attachments in each of these relationships show striking similarities at a basic functional level. The nature of these similarities suggests that they are produced by the same psychoneuroendocrine core, which appears to be present in all mammals. We also consider the development of each of kind of attachment. In contrast to fundamental similarities in the expression of attachment, their development in each case appears to be based on distinct, species-typical dispositions and constraints.

Psychoneuroendocrinology 1998 Nov;23(8):779-818
Neuroendocrine perspectives on social attachment and love.
Carter CS Department of Biology, University of Maryland, College Park
20742, USA. cc11@umail.umd.edu

The purpose of this paper is to review existing behavioral and neuroendocrine perspectives on social attachment and love. Both love and social attachments function to facilitate reproduction, provide a sense of safety, and reduce anxiety or stress. Because social attachment is an essential component of love, understanding attachment formation is an important step toward identifying the neurobiological substrates of love. Studies of pair bonding in monogamous rodents, such as prairie voles, and maternal attachment in precocial ungulates offer the most accessible animal models for the study of mechanisms underlying selective social attachments and the propensity to develop social bonds. Parental behavior and sexual behavior, even in the absence of selective social behaviors, are associated with the concept of love; the analysis of reproductive behaviors, which is far more extensive than our understanding of social attachment, also suggests neuroendocrine substrates for love. A review of these literatures reveals a recurrent association between high levels of activity in the hypothalamic pituitary adrenal (HPA) axis and the subsequent expression of social behaviors and attachments. Positive social behaviors, including social bonds, may reduce HPA axis activity, while in some cases negative social interactions can have the opposite effect. Central neuropeptides, and especially oxytocin and vasopressin have been implicated both in social bonding and in the central control of the HPA axis. In prairie voles, which show clear evidence of pair bonds, oxytocin is capable of increasing positive social behaviors and both oxytocin and social interactions reduce activity in the HPA axis. Social interactions and attachment involve endocrine systems capable of decreasing HPA reactivity and modulating the autonomic nervous system, perhaps accounting for health benefits that are attributed to loving relationships.

Psychoneuroendocrinology 1998 Nov;23(8):819-35
Oxytocin may mediate the benefits of positive social interaction and emotions.
Uvnas-Moberg K Department of Physiology and Pharmacology, Karolinska
Institute, Stockholm, Sweden. kerstin.uvnas-moberg@fyka.ki.se

During breastfeeding or suckling, maternal oxytocin levels are raised by somatosensory stimulation. Oxytocin may, however, also be released by nonnoxious stimuli such as touch, warm temperature etc. in plasma and in cerebrospinal fluid. Consequently, oxytocin may be involved in physiological and behavioral effects induced by social interaction in a more general context. In both male and female rats oxytocin exerts potent physiological antistress effects. If daily oxytocin injections are repeated over a 5-day period, blood pressure is decreased by 10-20 mmHg, the withdrawal latency to heat stimuli is prolonged, cortisol levels are decreased and insulin and cholecystokinin levels are increased. These effects last from 1 to several weeks after the last injection. After repeated oxytocin treatment weight gain may be promoted and the healing rate of wounds increased. Most behavioral and physiological effects induced by oxytocin can be blocked by oxytocin antagonists. In contrast, the antistress effects can not, suggesting that unidentified oxytocin receptors may exist. The prolonged latency in the tail-flick test can be temporarily reversed by administration of naloxone, suggesting that endogenous opioid activity has been increased by the oxytocin injections. In contrast, the long-term lowering of blood pressure and of cortisol levels as well as the sedative effects of oxytocin have been found to be related to an increased activity of central alpha 2-adrenoceptors. Positive social interactions have been related to health-promoting effects. Oxytocin released in response to social stimuli may be part of a neuroendocrine substrate which underlies the benefits of positive social experiences. Such processes may in addition explain the health-promoting effects of certain alternative therapies. Because of the special properties of oxytocin, including the fact that it can become conditioned to psychological state or imagery, oxytocin may also mediate the benefits attributed to therapies such as hypnosis or meditation.

Psychoneuroendocrinology 1998 Nov;23(8):837-61
Love: an emergent property of the mammalian autonomic nervous system.
Porges SW Institute for Child Study, University of Maryland, College Park
20742-1131, USA. sp37@umail.uml.edu

The evolution of the autonomic nervous system provides an organizing principle to interpret the adaptive significance of mammalian affective processes including courting, sexual arousal, copulation, and the establishment of enduring social bonds. According to the Polyvagal Theory (Porges, 1995, 1996, 1997), the well-documented phylogenetic shift in the neural regulation of the autonomic nervous system passes through three stages, each with an associated behavioral strategy. The first stage is characterized by a primitive unmyelinated visceral vagus that fosters digestion and responds to threat by depressing metabolic activity. Behaviorally, the first stage is associated with immobilization behaviors. The second stage is characterized by the sympathetic nervous system that is capable of increasing metabolic output and inhibiting the visceral vagus to foster mobilization behaviors necessary for 'fight or flight'. The third stage, unique to mammals, is characterized by a myelinated vagus that can rapidly regulate cardiac output to foster engagement and disengagement with the environment. The mammalian vagus is neuroanatomically linked to the cranial nerves that regulate social engagement via facial expression and vocalization. The Polyvagal Theory provides neurobiological explanations for two dimensions of intimacy: courting and the establishment of enduring pair-bonds. Courting is dependent upon the social engagement strategies associated with the mammalian vagus. The establishment of enduring pair-bonds is dependent upon a co-opting of the visceral vagus from an immobilization system associated with fear and avoidance to an immobilization system associated with safety and trust. The theory proposes that the phylogenetic development of the mammalian vagus is paralleled by a specialized communication, via oxytocin and vasopressin, between the hypothalamus and the medullary source nuclei of the viscera vagus, which facilitates sexual arousal, copulation, and the development of enduring pair-bonds.
 

Psychoneuroendocrinology 1998 Nov;23(8):989-1004
Oxytocin receptor mRNA expression in rat brain: implications for behavioral
integration and reproductive success.
Ostrowski NL Eli Lilly and Company, Lilly Corporate Headquarters,
Indianapolis, IN 46285, USA. nlo@lilly.com

The nonapeptide, oxytocin (OT), has been implicated in a wide range of physiological, behavioral and pharmacological effects related to learning and memory, parturition and lactation, maternal and sexual behavior, and the formation of social attachments. Specific G-protein linked membrane bound OT receptors mediate OTs effects. The unavailability of highly selective pharmacological ligands that discriminate the OT receptor from the highly homologous vasopressin receptors (V1a, V1b and V2 subtypes) has made it difficult to confirm specific effects of oxytocin, particularly in brain regions where OT and multiple AVP receptor subtypes may be coexpressed. Here, data on the oxytocin receptor (OTR) messenger ribonucleic acid (mRNA) localization in brain are presented in the context of a model that proposes a reproductive state-dependent role for steroid-hormone restructuring of neural circuits, and a role for oxytocin in the integration of neural transmission in pathways subserving: (1) steroid-sensitive reproductive behaviors; (2) learning; and (3) reinforcement. It is hypothesized that social attachments emerge as a consequence of a conditioned association between OT-related activity in these pathways and the eliciting stimulus.
 

Psychoneuroendocrinology 1998 Nov;23(8):963-87
Neurosteroids: a novel function of the brain.
Baulieu EE INSERM U 488, Le Kremlin-Bicetre, France. baulieu@kb.inserm.fr

Neurosteroids are synthetized in the central and peripheral nervous system, particularly but not exclusively in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources. They include 3-hydroxy-delta 5-compounds, such as pregnenolone (PREG) and dehydroepiandrosterone (DHEA), their sulfates, and reduced metabolites such as the tetrahydroderivative of progesterone 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha, 5 alpha-TH PROG). These compounds can act as allosteric modulators of neurotransmitter receptors, such as GABAA, NMDA and sigma receptors. Progesterone (PROG) is also a neurosteroid, and a progesterone receptor (PROG-R) has been identified in peripheral and central glial cells. At different places in the brain, neurosteroid concentrations vary according to environmental and behavioral circumstances, such as stress, sex recognition and aggressiveness. A physiological function of neurosteroids in the central nervous system is strongly suggested by the role of hippocampal PREGS with respect to memory, observed in aging rats. In the peripheral nervous system, a role for PROG synthesized in Schwann cells has been demonstrated in the repair of myelin after cryolesion of the sciatic nerve in vivo and in cultures of dorsal root ganglia neurites. It may be important to study the effect of abnormal neurosteroid concentrations/metabolism with a view to the possible treatment of functional and trophic disturbances of the nervous system.

Psychoneuroendocrinology 1998 Nov;23(8):945-62
Oxytocin and addiction: a review.
Kovacs GL, Sarnyai Z, Szabo G Central Laboratory, Markusovszky Teaching
Hospital, Hungary. glkovacs@mail.matav.hu

Neuropeptides affect adaptive central nervous system processes related to opiate ethanol and cocaine addiction. Oxytocin (OXT), a neurohypophyseal neuropeptide synthesized in the brain and released at the posterior pituitary, also is released in the central nervous system (CNS). OXT acts within the CNS and has been shown to inhibit the development of tolerance to morphine, and to attenuate various symptoms of morphine withdrawal in mice. In rats, intravenous self-administration of heroin was potently decreased by OXT treatment. In relation to cocaine abuse, OXT dose-dependently decreased cocaine-induced hyperlocomotion and stereotyped grooming behavior. Following chronic cocaine treatment, the behavioral tolerance to the sniffing-inducing effect of cocaine was markedly inhibited by OXT. Behavioral sensitization to cocaine, on the other hand, was facilitated by OXT. OXT receptors in the CNS--mainly those located in limbic and basal forebrain structures--are responsible for mediating various effects of OXT in the opiate- and cocaine-addicted organism. Dopaminergic neurotransmission--primarily in basal forebrain structures--is another important biochemical mediator of the central nervous system effects of OXT. Tolerance to ethanol (e.g. hypothermia-inducing effect of ethanol) also was inhibited by OXT.

Psychoneuroendocrinology 1998 Nov;23(8):927-44
Love as sensory stimulation: physiological consequences of its deprivation
and expression.
Komisaruk BR, Whipple B Department of Psychology, Rutgers, State University
of New Jersey, Newark 07102, USA. brk@andromeda.rutgers.edu

For the present purpose, love is defined as one's having stimulation that one desires. The nature of the stimulation can range on a continuum from the most abstract cognitive, to the most direct sensory, forms. Thus, this definition of love encompasses having an emotional bond with a person for whom one yearns, as well as having sensory stimulation that one desires. We address some of the physiological and perceptual consequences both of having, and of not having, love. We propose a neural mechanism by which deprivation of love may generate endogenous, compensatory sensory stimulation that manifests itself as psychosomatic illness. In addition, we propose a neuroendocrine mechanism underlying sexual response and orgasm. The latter includes vaginocervical sensory pathways to the brain that can produce analgesia, release oxytocin, and/or bypass the spinal cord via the vagus nerve. We present evidence of the existence of non-genital orgasms, which suggests that genital orgasm is a special case of a more pervasive orgasmic process. Through recent studies, the mechanisms and manifestations of love and its deprivation are becoming better understood. The better is our understanding of love, the greater is our respect for the significance and potency of its role in mental and physical health.

Psychoneuroendocrinology 1998 Nov;23(8):905-26
Role of the vomeronasal input in maternal behavior.
Del Cerro MC Department of Psychobiology, Psychology School, U.N.E.D.,
Ciudad Universitaria s/n, Madrid, Spain. delcerro@cu.uned.es

This article reviews the role of the vomeronasal system in the induction of parental behavior in female and male rats, using, primarily, the sensitization model. The following questions are addressed: (1) Is the vomeronasal system sexually dimorphic? (2) Do the sex differences found in the VNS underlie those seen in behavior? (3) Do mechanisms, other than the classical 'organizational' effects of perinatal gonadal steroids, play a role in the organization of behavioral phenotypes in parental behavior? and (4) Does vomeronasal input play a role in the formation of the mother infant bond in humans? The first question has been answered throughout the 1980's in various studies of the organizational actions of postnatal exposure to gonadal steroids. The second aim has been addressed in a functional approach by lesion and neural activation studies. The experiments which lead us to consider the hypothesis that nonsteroidal factors in development, and specifically GABA, could account for the expression of parental care are reviewed. Finally, research relevant to the existence of a vomeronasal organ in humans and a possible pheromonal input in the formation of mother-infant bonds in humans is reviewed.

Psychoneuroendocrinology 1998 Nov;23(8):891-904
Social relationships and the management of stress.
Sachser N, Durschlag M, Hirzel D Westfalische Wilhelms-Universitat Munster,
Abteilung fur Verhaltensbiologie, FRG. sachser@uni-muenster.de

Two different types of social relationships exist in mammalian social systems: dominance relationships and social bondings. This article shows that both are crucial for the management of stress. The following general conclusions are derived: (1) In stable social systems, established dominance relationships result in predictable behaviour. As a consequence, low positions in the hierarchy do not necessarily lead to enhanced endocrine stress responses. Under conditions of instability, however, distinct increases in the activities of the pituitary-adrenocortical- and the sympathetic-adrenomedullary systems are found; (2) The ability to establish and to respect dominance relationships is a prerequisite to build up stable social systems. Whether this ability is realized, however, depends on social experiences made during behavioural development. The time around puberty seems to be essential for the acquisition of those social skills needed to adapt to unfamiliar conspecifics in a non-stressful and non-aggressive way; (3) Stress responses can be ameliorated by the presence of members of the same species. This phenomenon is called social support. In general, social support cannot be provided by any conspecific, but the ability to give social support is restricted to bonding partners. In most mammalian species mothers are important bonding partners for their infants. In some species bondings also occur between adult individuals; and (4) On a physiological level the bonding partner reduces the activities of the pituitary-adrenocortical- and the sympathetic-adrenomedullary systems. On a psychological level he/she can be regarded as a 'security-giving and arousal-reducing structure'. This is true irrespective of whether the bonding partner is the mother, in the case of an infant, or a male or a female in the case of an adult individual.

Psychoneuroendocrinology 1998 Nov;23(8):877-90
Social isolation and cardiovascular disease: an atherosclerotic pathway?
Knox SS, Uvnas-Moberg K Division of Epidemiology and Clinical Applications,
National Heart, Lung, and Blood Institute, II Rockledge Center, Bethesda,
MD 20892-7936, USA. sarah_knox@nih.gov

This paper outlines two pathways through which social support can influence the prevention or progression of cardiovascular disease: health behaviors and neuroendocrine mechanisms. Its primary focus is on neuroendocrine pathways, reviewing data which suggest that lack of social support is etiologically related to coronary artery lesion development through two mechanisms: sympathetic-adrenomedullary influences on platelet function, heart rate and blood pressure in the initial endothelial injury; and pituitary-adrenal cortical factors involved in smooth muscle cell proliferation during progression of the lesion after injury has taken place. It hypothesizes that the buffering effect of social support on the cardiovascular system is mediated primarily through mechanisms associated with the release of oxytocin.

Psychoneuroendocrinology 1998 Nov;23(8):863-75
Effects of early stress on adult affiliative behavior.
Henry JP, Wang S Department of Nephrology/Hypertension, Charles Drew
University, Los Angeles, CA 90059, USA.

The recently evolved mammalian species preservative behavior as opposed to the ancient self preservative behavior involves parental care, nursing, social interaction, pair bonding and mutual defense. Gonadal steroids together with oxytocin are critical for this affiliative, attachment behavior. When there is stressful loss of control, gonadotrophins are diminished, and the self preservative, fight-flight catecholamine coping response takes priority. It is suggested that self preservation is associated with left hemispheric brain function and that species preservation is associated with right hemispheric function. Stress during infancy that is severe enough to create insecure attachment has a dissociative effect, disrupting right hemispheric emotional functioning and species preservative behavior, and a permanent bias towards self preservation can become an adult trait. In such a person with impaired affiliation, corticoid responses may be deficient. The coronary type A behavior pattern common in our society exhibits some of this deficiency in species preservative activity.