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).”

“…“it is conceivable that brain circuits for separation distress represent an evolutionary elaboration of an endorphin-based pain network” (p. 219), and Nelson and Panksepp (1998) stated, “The pain components made stronger contributions to the subcomponents which aroused emotional distress during…”

“For example, thirst may be said to be caused by brain receptors for angiotensin II, and social motivations, such as attachment, have been suggested to be caused by activating brain peptide receptors for oxytocin and vasopressin [105,162].”

“We proceeded to demonstrate that social bonding from the infantÕs perspective was also oxytocin-facilitated in rats (Nelson & Panksepp, 1996, 1998).”

“neurochemical effects of prolonged social isolation (Nelson and Panksepp, 1998) and long-term changes in 5-HT function are observed in monkeys raised in a poor environment (Clarke et al.”

“Such findings suggest that opiates provide a critical part of the neural basis on which primate sociality has evolved (Keverne et al. 1989; Nelson & Panksepp 1998; Panksepp et al. 1994).”

“…response to novel and emotionally salient stimuli (Watkins and Mayer, 1982; Akil et al., 1984; Kalin et al., 1988; Rubinstein et al., 1996; Sora et al., 1997; Nelson and Panksepp, 1998; Smith et al., 1998; Filliol et al., 2000; Drolet et al., 2001; Zubieta et al., 2001, 2003a; Moles et al., 2004).”

“…has also accumulated as to the involvement of this neurotransmitter system in the adaptation and response to novel and emotionally salient stimuli in both animal models and humans (Kalin et al., 1988; Nelson and Panksepp, 1998; Filliol et al., 2000; Zubieta et al., 2003b; Moles et al., 2004).”

“…postpartum behavior, including gaze, positive affect, " motherese " vocalizations, and affectionate touch, suggesting that OT across gestation functions to prime mothers for the expression of maternal behavior, consistent with the effects described in other mammals (Nelson and Panksepp, 1998).”

“…release of OT and its role in controlling behavior are diverse, although there are some similarities across species, such as lactation’s milk ejection reflex, affiliation, pain reduction, and stress reduction (Carter, 2003; Nelson & Panksepp, 1998; Neumann, 2008; Onaka, 2004; Young & Zingg, 2009).”

“Many brain areas with oxytocin receptors are involved in behavior, memory, sensory processing, eating, satiety (Nelson and Panksepp, 1998), and reproduction.”

“Nichols and Stich (2003) and Goldman (2006) each maintain, in contrast, that introspection is intact in autism, with difficulties in otherunderstanding arising from difficulties in supposing or empathizing.”

“…may be roles for other hormones both in promoting social support initially and in regulating its biological eff ects, which include vasopressin, norepinephrine, serotonin, prolactin, and endogenous opioid peptides (Nelson & Panksepp, 1998 ; Taylor et al., 2002 ). why is social support beneficial?”

“Such findings suggest that nAChRs may additionally regulate the early maturation of these neuronal pathways which play pivotal roles in regulating arousal, maternal bonding, and autonomic function during the perinatal period (Nelson and Panksepp, 1998; Itoi, 2008).”

“…cingulate cortex (ACC) functions as a neural alarm system to warn people that factors in their environment threaten their goals (Eisenberger, Lieberman, & Williams, 2003; Eisenberger & Lieberman, 2004; Nelson & Panksepp, 1998; Bush, Luu, & Posner, 2000; Kimbrell, George, Parekh, et al., 1999).”

“Imprinting, the learning process it accesses, is described by Petrovich and Gewirtz (1985) as synchrony between sequential infant maternal stimuli and behavior (see Schore, 1994 and Nelson & Panksepp, 1998 for models of the neurochemistry of attachment).”

“From this concordance, we would hypothesize that music may arouse that neuropeptide system, one of the best established social-emotional sys- tems of the vertebrate brain (Carter, 1998; Insel, 1997; Nelson and Panksepp, 1998).”

“Nelson and Panksepp (1998) suggest that hormonal changes in the mother across gestation, particularly in OT and prolactin, prime the initiation of maternal behavior following birth and provide the basis for the development of contingent parenting.”

“Opioid modulation of isolation-induced USV in neonatal rats has been reported by several authors (Carden et al., 1991; Kehoe and Blass, 1986; Nelson and Panksepp, 1998).”

“…brain nd behavioral organization are considered particularly amenable o specific types of information during specific developmental indows (Nelson and Panksepp, 1998; Bell et al., 2010; Meaney, 010; Nelson and Guyer, 2011; Crone and Dahl, 2012; Takesian nd Hensch, 2013; Nelson et al.,…”

“Several neurochemicals are associated with attachment, but the best evidence is available for four substances: oxytocin, norepinephrine, vasopressin and endogenous opioids (Nelson and Panksepp, 1998).”

“Furthermore, the opioid theory of social affiliation (Depue & Morrone-Strupinsky, 2005; Nelson & Panksepp, 1998; Panksepp et al. 1997) posits that the rewarding effects of social contact facilitate learning and funnel attention toward social stimuli and may produce social “addiction” or attachment.”

“Furthermore, maternal OXT functioning influences reciprocal affective behaviors between mother and offspring in mammalian species (Nelson and Panksepp, 1998).”

“…neurochemistries that could powerfully and specifically alleviate the pain of separation distress (namely opioids, oxytocin, and prolactin) could serve as affective substrates for the construction of social bonds andmore subtle prosocial feelings (Nelson & Panksepp, 1998; Panksepp, 1981a, 1998a).”

“These parallels provide strong evidence for a link between attachment and addiction (MacLean 1990; Nelson and Panksepp 1998; Insel 2003; Fisher 2004; Reynaud et al. 2010).”

“…including social stress (e.g., Onaka, 2004), it has been christened the “cuddle hormone” because hugs, kisses, and other affectionate types of touch increase the release of oxytocin (e.g., Insel, 1992, 1997; Nelson & Panksepp, 1998; Uvnäs-Moberg, 1997; UvnäsMoberg, Arn, & Magnusson, 2005).”

“Additionally, the data do not explainwhy some species display bonding behaviour and others do not, since it is believed that all mammals have genes encoding oxytocin and the OTR, as both are necessary for lactation (Nishimori et al. 1996).”

“This is an example of the early symbiotic biological relationship between the dyad (24,25).”

“Nevertheless, conservation of neural structure and function across mammals suggests that bond-related neural phenomena may characterize more than the few mammalian species that have been studied (Nelson & Panksepp, 1998).”

“…of distress (e.g., Corticotrophin Releasing Factor) and those that can powerfully alleviate distress (e.g., brain opioids, oxytocin, and prolactin) figure heavily in the genesis of social attachments (as well as sexuality and nurturance) and may ameliorate depression (Nelson and Panksepp, 1998).”

“In primates, endorphin release is triggered by grooming (Keverne et al., 1989) and appears to be deeply involved in the processes involved in social bonding at the dyadic level (Nelson and Panksepp, 1998; Dunbar, 2010; Machin and Dunbar, 2011).”

“Second, this modulation occurs in brain regions involved in positive emotions and motivation (for neuroanatomical and pharmacological analyses of maternal behavior, social play and sexual behavior, see Everitt, 1990; Everitt and Stacey, 1987; Fleming et al., 1999; Grimm and Bridges, 1983; Kristal, 2009; Nelson and Pan…”

“Repeated-measure analysis of variance (ANOVA) for the four ather (log)OT assessments with condition and infant gender as the etween-subject factors revealed different pattern in the two conitions, F (1,33) 189.”

“…– which along with opioids inhibit the separation calls of infants – in maternal care suggests that social and maternal comfort are produced by the same brain chemistries that help to mediate sexual behaviour (Nelson and Panksepp, 1998; Panksepp, 1998; Panksepp, 2005; Panksepp and Biven, 2012).”

“Research in animals has pointed to the role of oxytocin and prolactin in the initiation of maternal behavior, such as affiliative touch, grooming, and proximity seeking (Grattan et al., 2001; Insel, 1997; Nelson & Panksepp, 1998).”

“Oxytocin becomes a major candidate as a potential alleviator of depression in its role of being a major modulator of separation distress (Panksepp, 1998) and, next to opiates, the best candidate for a key mediator of social attachments (Nelson & Panksepp, 1998).”

“In mammals there is evidence of direct and indirect participation of hormones and neurochemicals, such as estradiol, oxytocin, prolactin, vasopressin, and several endogenous opioids in the initiation and maintenance of the motheryoung bond [45].”

“Thus, they are considerably less distressed by the social separation that is inherent in the majority of these studies (Nelson and Panksepp, 1998; van den Berg et al., 1999).”

“In summary, while evidence is primarily correlational, BOTSA illustrates that for humans both social attachment and the administration of exogenous opiates have similar neurophysiological effects (Nelson & Panksepp 1998; Nummenmaa et al. 2016).”

“n addition, the neuropeptides vasopressin (AVP) and oxytocin OT) have attracted a lot of interest, due to the evidence that they re involved in regulating social attachment behavior in rodents nd non-human primates [39,41,42,49,70,92,120,121].”

“…(e.g., Eisenberger & Lieberman, 2005) and social pain theory (MacDonald, Kingsbury, & Shaw, 2005; MacDonald & Leary, 2005) suggest that a system capable of detecting and responding to social pain “piggybacked” onto the preexisting physicalpain system during evolution (Nelson & Panksepp, 1998).”

“Processes of reward and memory established in early childhood enhanced the capacity to affiliate with others (Depue & Morrone-Strupinsky, 2005; Nelson & Panksepp, 1998).”

“If antepartum activities are somewhat predictive of postpartum maternal care [55,26,3], even a moderate behavioural change in maternal behaviour may potentially have significant consequences for offspring development.”

“Further, Brattleboro neonates show disturbances in early odor orienting (Nelson and Panksepp, 1998) and dysregulation of the HPA axis in response to maternal separation as neonates (Fodor and Zelena, 2014).”

“The salient behaviours expressing separation distress include specific vocalisations, and the affiliative behaviours include rough and tumble play, sexual and parental behaviours, and various forms of physical contact including allogrooming (Nelson and Panksepp 1998).”

“Changes in oxytocin receptors may be related to induction of maternal behavior: administration of oxytocin to virgin female rats results in a sudden surge of maternal behavior; blocking oxytocin in new rat mothers interferes with maternal behavior (Nelson & Panksepp, 1998).”

“That is, infant cries and caregiver responses to them constitute an integrated dyadic system that encompasses the infant production of cries as well as the adult anatomy (9–12), physiology (5, 13), and perception, processing, and response apparatus to cries (2, 4, 5, 14–17).”

“2003; Field 1995), which stimulates oxytocin and in turn may have a positive effect on attachment (Nelson and Panksepp 1998).”

“In this period immediately after birth, the emotional brain and the social brain are being connected (Nelson & Panksepp, 1998).”

“…oxytocin in both maternal behavior and in adult pairbonding, in humans as well as in other animals (see, e.g., Carter, 1998; Insel, 1997; Nelson & Panksepp, 1998; Üvnas-Moberg, 1998), lends additional credence to the evolutionary relationship suggested here between mother-infant…”

“Indeed, such studies have clarified some neurological foundations of behaviourally linked positive affects, and this is specifically the case for some aspects of exploratory and feeding (Ikemoto and Panksepp 1999; Berridge and Robinson 2003; Panksepp and Zellner 2004), bonding and bond affirming (Nelson and Panksepp 1…”

“This evolutionary, neurobiologic attachment theory has received much empirical support (Nelson and Panksepp, 1998).”

“From a mechanistic perspective, it can be hypothesized on the basis of previous research that the Affect Module stimulates positive affect systems (37) linked to care and affiliation and modulated by oxytocin and opiates (38, 39).”

“Based on similarities between opiate addiction and social attachment, Panksepp and colleagues (Panksepp et al., 1980; Nelson and Panksepp, 1998) have hypothesized that endogenous opioids mediate the rewarding properties of social affiliation.”

“…functions (Smith et al., 1998; Drolet et al., 2001), and the adaptation and response to novel and emotionally salient stimuli in animal models (Kalin et al., 1988; Nelson and Panksepp, 1998; Filliol et al., 2000b; Moles et al., 2004) and more recently in humans (Zubieta et al., 2003b).”