Brain substrates of infant-mother attachment: contributions of opioids, oxytocin, and norepinephrine.

“erections, lordosis), administration of a vasopressin antagonist after copulation prevented the formation of post-copulatory pair bonds in the male Prairie vole and, in the absence of copulation, vasopressin administration was found to induce pair-bond formation in this species (212).”

“, and Gross, E. B. (2013). Felt understanding and misunderstanding affect the perception of pain, slant, and distance.”

“Early pharmacological studies suggested that endogenous opioids are released in the infant during caretaking and that this serves to motivate it to seek out and maintain closeness to its caregiver (Kehoe and Blass, 1986; Kalin et al., 1988; Carden et al., 1991; Nelson and Panksepp, 1998).”

“A number of behavioural studies have collectively demonstrated that oxytocin facilitates affiliative behaviour (Insel, 1992; Nelson & Panksepp, 1998; Young et al., 2001) and inhibits aggression (Harmon et al., 2002; Lubin et al., 2003), and vasopressin facilitates aggression (Ferris & Potegal,…”

“Oxt is known to interact with dopamine, norepinephrine and opioids in the early postpartum period to affect maternal care (Nelson & Panksepp 1998; Rutherford et al. 2011; Shahrokh et al. 2010), but the exact locations of these interactions remain areas for future study.”

“between mother and infant, partlydue to regulationof adecrease in blood pressure and cortisol levels upon commencement of suckling in mammals (Insel, 1992; Nelson and Panksepp, 1998 ) and during breastfeeding in human women, with accompanying positive emotion (Uvnas-Moberg, 1998).”

“Different brain substrates of infant–mother attachment have been identified, the opioid system being one of the possible mediators.(11) We have already demonstrated(12) that mice lacking m-opioid receptors show deficits in two independent measures of attachment behavior: knockout pups were not”

“In recent years, cross-species research has demonstrated that several evolutionarily conserved neuropeptides play a key role in diverse social behaviors (Nelson and Panksepp, 1998; Ferguson et al., 2000; Insel and Young, 2001; Panksepp, 2009; Bos et al., 2012).”

“Opioids also contribute to the onset and maintenance of maternal behavior, not only because of the interaction with oxytocin but also almost certainly because of the importance of opioids to motivation and reward (Nelson and Panksepp 1998; Panksepp et al. 1994) and to pain and hypoalgesia.”

“An alternative explanation—one that we favor—is that OT and opioids are not mutually exclusive when it comes to primate social bonding (see Nelson and Panksepp, 1998).”

“Similar hormonal-behavioral relations have been documented in other mammalian species (Insel, 1997; Nelson & Panksepp, 1998).”

“The “integration of emotional systems for social affect” is a critical need (Nelson & Panksepp, 1998), and it qualifies as critical in terms of timing in that the window of opportunity is in the first 1,000 min.”

“Endogenous opioids appear to have a role in mother‐infant attachment (Panksepp et al. 1994; Nelson and Panksepp 1998 ) as well as in physiological and behavioral responses to stress (Akil et al. 1984).”

“Researchers have also proposed neurobiological models explaining how processes of dyadic attunement would be reflected in a physiological synchrony (Nelson and Panksepp 1998; Feldman 2007b; Schore 2000).”

“Moreover, nest building was shown to be dopamine- and enkephalin-dependent [43].”

“…hormone oxytocin, commonly referred to as the ‘love’ or attachment hormone due to its social bonding effects (Campbell, 2008; Kosfeld et al., 2005; Nelson & Panksepp, 1998), has been shown to aid social information processing in many neurodevelopmental groups (Keech et al., 2018; Wang et al.,…”

“The catecholamine norepinephrine (NE) has also been implicated in affiliative behavior, particularly with respect to learning and memory of preferred individuals (Nelson and Panksepp, 1998).”

“Accumulating evidence suggests that oxytocin-, vasopressin-, and opioid-modulated mesocorticolimbic dopaminergic pathway activity accounts for the rewarding aspects of social interactions (Insel, 1997; Nelson and Panksepp, 1998).”

“…that oxytocin promotes the arousal of the basic emotional systems for maternal CARE while reducing PANIC (or separation-distress) arousal within the brain (Nelson and Panksepp, 1998; Panksepp and Watt, 2011; Eapen et al., 2014), and potentially directly promote positive affect (IsHak et al., 2011).”

“Because of the adaptive value of mammalian social bonds, the social attachment systems, which keep young near caregivers, may have become associated with the physical pain system to promote survival (21), alerting us when we have sustained injury to our social connections and, thus allowing restorative measures to be…”

“The presently observed results are in line with prior PET studies indicating a crucial role of the mu opioid system for attachment and sociability in humans (25,26,55-57) and suggest that there are similar parallels in the opioid basis of the attachment system across primates and other mammals (1,19).”

“Endogenous opioid activity, particularly in the dorsal ACC (dACC), may inhibit threat detection (Nelson and Panksepp, 1998).”

“For instance, a large body of evidence suggest that OT and AVP are involved in the establishment of social behaviour early in life, such as mother–pup interactions, maternal behaviour and social bonding (Insel and Shapiro, 1992; Nelson and Panksepp, 1998; Insel, 2003; Carter et al., 2008) and also in the regulation of…”

“Exogenous opioid agonists (such as morphine or opium) act similarly to endogenous opioids, such as endorphins (Belluzzi and Stein 1977; D’Amato and Pavone, 1993; Nelson and Panksepp 1998; Stefano et al. 2000), in that they act at the level of the spinal cord to inhibit pain transmission (Fields 2007).”

“Recent developments in neuroscience have suggested that many social behaviors, such as attachment and affiliation, may be mediated in part by common brain circuits involving primarily limbic and brainstem regions ( Nelson & Panksepp, 1998 ).”

“MacDonald and Leary’s (2005) seminal article, which utilized a large amount of work from the animal model literature by Jaak Panksepp and others (e.g., Herman & Panksepp, 1978; Nelson & Panksepp, 1998), promoted enormous interest in the social and physical pain overlap.”

“Opioid neurotransmission is implicated in response and adaptation to emotionally salient stimuli in both animal models and human studies (Filliol et al. 2000; Kalin et al. 1988; Moles et al. 2004; Nelson and Panksepp 1998; Zubieta et al. 2003).”

“The neuropeptide OT has been implicated in the formation of social bonds, in addition to other important physiological functions such as lactation and parturition (Carter, 1998; Nelson and Panksepp, 1998).”

“While there has been considerable research on attachment neurobiology in adults focusing on mates and reproduction, the infant has received little attention (29, 64, 65)).”

“The mechanism of the comforting effect of breastfeeding and KMC is likely related to the release of oxytocin [78,79].”

“…1996) and it is also involved in other social behaviors, such as maternal behavior, female sexual behavior and social attachment (Insel, 1992; Nelson and Panksepp, 1998; Cushing and Carter, 1999; Pfaff et al., 1999), that have been shown to be disrupted by ethanol exposure during C© The…”

“Because of the adaptive value of mammalian social bonds, the social attachment systems which keep the young near their caregivers may have become associated with the physical pain system to promote survival (35), alerting humans to when they have sustained ‘injury’ to their social connections and, thus, allowing resto…”

“These peptides have important roles early in life, for example they are vital for the establishment of early social behavior and several reports describe the role for oxytocin and vasopressin in maternal behavior, motherpup interactions, and social bonding (Insel and Shapiro, 1992a,b; Nelson and Panksepp, 1998; Insel,…”

“From this, it has been suggested that opioid mechanisms may be one neural substrate common to both physical and social pain [Nelson & Panksepp, 1998; reviewed in Panksepp, 1998].”

“Most tend to call this love, and we should certainly consider that this type of mind-brain process arises largely from the underlying neurobiology of basic mammalian attachment processes (Carter, 1998; Nelson & Panksepp, 1998).”

“Across a wide variety of species, maternal separation induces HPA axis activity (Coe et al., 1985; Kalin et al., 1988; Bayart et al., 1990; Wiener et al., 1990; Higley et al., 1992; Dettling et al., 1998, 2002; Nelson and Panksepp, 1998; Barr et al., 2004b).”

“Second, the differential response of LPA and HPA lambs to weaning may be mediated by differences in oxytocin concentrations, the main hormone promoting mammal offspring affiliative bond (Nelson and Panksepp, 1998; Nowak and Boivin, 2015).”

“At the moment it is not clear whether these feelings of warmth in the chest are associated with an actual objective temperature increase, or whether participants embody the metaphor of communality and feel social warmth (see [6, 54, 55]).”

“In addition, opiates have been suggested to play a role in primate sociality (Nelson and Panksepp, 1998; Depue and Morrone-Strupinsky, 2005), and m-opioid receptors (mORs) have been implicated in feelings of interpersonal warmth and decreased incentive motivation accompanying close interpersonal relationships (Depue a…”

“Nelson and Panksepp (1998) have argued that individuals seek to obtain an optimal opioidergic tone, which can be modulated by an attachment figure.”

“Endogenous opioids in offspring are released during social contact and low levels have been shown to induce behaviors to seek out contact from a caregiver (Nelson and Panksepp, 1998).”

“…role in regulating healthy affiliative behavior across species, as suggested by studies in rodents (Moles et al., 2004; Resendez et al., 2013; Briand et al., 2015), as well as in both human and non-human primates (Nelson and Panksepp, 1998; Barr et al., 2008; Troisi et al., 2011; Hsu et al., 2013).”

“Rodent studies have shown that the endogenous opioid system is intimately involved in mother– infant bonding, controlling both mother behaviors and pups’ responses (Nelson & Panksepp, 1998; Panksepp et al. 1980).”

“The dACC is a key structure associated with the affective component of pain (see Apkarian et al., 2005 for a review) and functions as a “neural alarm system” for physical threats (Nelson and Panksepp, 1988; Bush et al., 2000; Eisenberger and Lieberman, 2004).”

“…typical safety signals block the opioid processes necessary for fear learning (Wiertelak, Maier, & Watkins, 1992), social-support figures are thought to trigger the release of endogenous opioids (Nelson & Panksepp, 1998), perhaps enabling them to reduce fear acquisition and enhance fear extinction.”

“From his observations of dogs, Scott (1963, 1987) speculated that dogs who prefer other dogs to humans and who run away and hide when a stranger appears, as Beauly did, had a lack of exposure to humans during a critical period of development. Fischer-Mamblona (2000) refers to this as ‘a break in the early attachment p…”

“Panksepp has shown that the pain system, an endowment of all animals to protect against tissue damage, has been adapted by social animals such as humans to modulate relatedness (Nelson and Panksepp, 1998).”

“When elevated in the bloodstream, endorphins produce an opiate-like state that has mild analgesic effects [63].”

“Similar effects have been seen in young dogs, chickens, and primates: opioid drugs reduce separation distress, even at doses too low to cause sedation or other effects (Nelson & Panksepp, 1998).”

“In addition to the effects on analgesia and reward, the opiate system has been proposed to play an important role in modulating social reward, including maternal behavior, social motivation, and social attachments (Nelson and Panksepp, 1998).”

“This is reasonable, given the effectiveness of opioids in alleviating both physical pain and separation distress (Kalin et al., 1988; Nelson and Panksepp, 1998) in several species.”

“A strong body of evidence suggests that the neurophysiological basis for infant attachment and distress responses would be regulated by the release of endogenous opioids (Nelson and Panksepp, 1998; Gray et al., 2000; Weller and Feldman, 2003).”

“The opiate system is involved in social attachment, maternal bonding, social learning, and sexual reward (Nelson and Panksepp, 1998; Panksepp et al., 1980).”

“Certain changes also occur in the development of receptor systems and secretion of several mediators and hormones, in particular, of oxytocin (Insel, 1997; Nelson and Panksepp, 1998).”

“Indeed, the maternal neural system is involved in active ‘crosstalk’ with the fear/ anxiety-mediating neural system (Fleming et al, 1980, 1988, 1989; Fleming and Luebke, 1981) and is modulated by endogenous opioids (Mayer et al, 1985; Panksepp et al, 1994; Zaias et al, 1996; Nelson and Panksepp, 1998; Byrnes and Bridg…”