Brain Substrates of Infant–Mother Attachment: Contributions of Opioids, Oxytocin, and Norepinephrine ERIC E. NELSON a , * AND JAAK PANKSEPP b a Department of Psychology, Indiana University, Bloomington, IN 47405, USA b Department of Psychology, Bowling Green State University, Bowling Green, OH 43403, USA NELSON, E. E., PANKSEPP, J. Brain substrates of infant–mother attachment: contributions of opioids, oxytocin, and norepinephrine. NEUROSCI BIOBEHAV REV 22(3) 437–452, 1998.—The aim of this paper is to review recent work concerning the psychobiological substrates of social bonding, focusing on the literature attributed to opioids, oxytocin and norepinephrine in rats. Existing evidence and thinking about the biological foundations of attachment in young mammalian species and the neurobiology of several other affiliative behaviors including maternal behavior, sexual behavior and social memory is reviewed. We postulate the existence of social motivation circuitry which is common to all mammals and consistent across development. Oxytocin, vasopressin, endogenous opioids and catecholamines appear to participate in a wide variety of affiliative behaviors and are likely to be important components in this circuitry. It is proposed that these same neurochemical and neuroanatomical patterns will emerge as key substrates in the neurobiology of infant attachments to their caregivers.  1998 Elsevier Science Ltd. All rights reserved. INTRODUCTION MAMMALIAN INFANTS display affiliative behaviors and form ‘attachment bonds’ with their caregivers. These bonds are characterized by selective approach and interaction with specific individuals, and display of affective distress during acute periods of separation from these individuals. It has been theorized that social attachment serves to maintain close physical proximity and elicit care from a primary caregiver, which in turn increases the probability of the young surviving to maturity and reproducing (27). Although the evolutionary advantages of attachment have been discussed for some time, only recently have specific mechanistic hypotheses been advanced concerning the underlying neural substrates of these behaviors (174). The research precedents for the existence of attachment systems in the brain were established by the well-known behavioral research programs of Harry Harlow (72–74) and John Paul Scott (181,181), which will not be detailed here. We believe that the neural mechanisms which underlie attachment are organized into a socially directed motiva- tional system within the brain (151,174). This neural system emerges in infancy and continues to modulate affiliative behaviors throughout the life-span. Although the level of social activity varies greatly in adults of different species (50), all mammals engage in some degree of affiliative behavior after weaning. Such behaviors range from rough and tumble play (57,161), to sexual and parental behaviors (107,111), to maintenance of group cohesiveness (5). Several anatomical and neurochemical similarities have been found in these varied affiliative behaviors across species, which suggest the existence of a common neural system. We believe the ontogenetic roots of this affiliative system may be found in infant social attachment. The focus of this paper will be on the mechanistic nature of attachment processes in the brains of infant animals. We will attempt to integrate the literature on rat pup attachment with data on the neural substrates of adult affiliative behavior, and will assert that infant–mother attachment shares many neural substrates with affiliative and attach- ment behaviors expressed in adults. Cross-species and cross-situational generality have been identified for oxy- tocin, endogenous opioids, and norepinephrine. This is not meant to be a comprehensive review of the literature on the neural substrates of affiliative behavior. Our purpose is merely to suggest that sufficient evidence exists to include these three neurochemical systems as a part of a neural circuit which regulates affiliative and attachment behaviors across mammalian species and across development. One critical conceptual question which we hope will emerge from the present discussion is whether there is a single or multiple evolutionary antecedents for attachment. If there is no single source process, but rather, the con- verging influences of multiple processes (Fig. 1), such as the contributory effects of contact comfort, energy and thermoregulatory effects, as well as other forms of Neuroscience and Biobehavioral Reviews, Vol. 22, No. 3, pp. 437–452, 1998  1998 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0149-7634/98 $19.00 + 0.00 PII: S0149-7634(97)00052-3 Pergamon 437 * Corresponding author.