Opioid‐mediation of separation distress in 10‐day‐old rats: Reversal of stress with maternal stimuli

Kehoe, Priscilla; Blass, Elliott M.

doi:10.1002/dev.420190410

Cited by 220 publications

(165 citation statements)

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“…The actions of anxiolytic and anxiogenic compounds on USV are generally compatible with this explanation [56,68,83,116,119]. Other behaviors that have been considered indicators of distress accompany USV, e.g., increases in locomotor activity, self grooming, and micturation [68].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 73%

Acquisition and expression of a socially mediated separation response

Shair¹

2007

Behavioural Brain Research

108

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INTRODUCTIONSocial bonds are made up of numerous subsystems mediating the overall social relationships that develop between infants and caretakers. The effects of an infant's formation of early life relationships and its social interactions with caretakers are known to last well in to adulthood with both beneficial and harmful effects [28,35,70]. In our laboratory, we study the development of social relationships between infant rats and their dams, sires, and littermates using an isolation, reunion, and re-isolation test paradigm.Infant rats emit ultrasonic vocalizations (USV) in a variety of situations, including as a response to isolation, physical manipulation, and thermal and olfactory challenge [1][2][3]6,19,25,46,79,80,82,97]. Many researchers have used the presence and absence of these sounds to make inferences about the internal state of the rodents, e.g., isolation-induced USV's have often been called "distress vocalizations" [29,76,78].The isolation-induced vocalization of a rat pup is modulated both by current social interactions and by the pup's rearing experience. This modulation of USV by social interactions provides a paradigm for investigating the neurobehavioral mechanisms underlying acquisition and expression of infant attachment. What is maternal potentiation of isolation-induced vocalizations of infant rats?Maternal potentiation of ultrasonic vocalization occurs when, after a brief contact with the dam, isolated infant rats produce USV at a rate significantly higher than they would during an isolation not preceded by dam contact. Although the definition may seem of narrow interest, there is a growing belief that the potentiation phenomenon has broad applicability for the study of early life social relationships in many species. But before going further, the reader needs to understand the usual test paradigm in our laboratory.Developmental Psychobiology, Unit 40, New York State Psychiatric Institute, 1051 Riverside Dr. NY, NY 100032, Tele 212-543-5695, Fax 212-543-5467, hns1@columbia.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTest procedure-On the day of testing, the dam is removed from the home cage and anesthetized. The litter is allowed to adapt to her removal for ~15-20min in the home cage on a thermoregulated heating pad. Then, each pup is tested in turn. The pup is picked up and placed alone in a clean polycarbonate rectangular box (18 × 21 × 20 cm) at room temperature. The test consists of three periods, which can range from 1-5min in length (3mi...

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Section: Nih-pa Author Manuscriptmentioning

confidence: 73%

Acquisition and expression of a socially mediated separation response

Shair¹

2007

Behavioural Brain Research

108

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“…Specifically in the rat neonate, opioids facilitate odor preference learning (Barr & Rossi, 1992;Kehoe & Blass, 1986a;Panksepp, Nelson, & Siviy, 1994;Randall, Kraemer, Dose, Carbary, & Bardo, 1992;Roth & Sullivan, 2001Shide & Blass, 1991), and nipple-milk conditioning (Petrov, Varlinskaya, Becker, & Smotherman, 1998, Petrov, Varlinskaya, & Smotherman, 2000Robinson, Arnold, Spear, & Smotherman, 1993;Robinson & Smotherman, 1997). Suggestive of their rewarding value in neonates, opioids are sufficient to alleviate separation distress (Carden, Barr, & Hofer, 1991;Goodwin, Molina, & Spear, 1994;Kehoe & Blass, 1986b;Panksepp, Herman, Conner, Bishop, & Scott, 1978). Additionally, Moles, Kieffer, and D'Amota (2004) have recently demonstrated that mice neonates lacking m-opioid receptors fail to show preferences toward maternal odor and do not show distress when separated from the mother, indicative that opioids play a prominent role in modulating the rewarding experience of mother-infant interactions.…”

Section: Discussionmentioning

confidence: 99%

Examining the role of endogenous opioids in learned odor–stroke associations in infant rats

Roth

Sullivan

2005

Developmental Psychobiology

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Maternal touch profoundly regulates infant neural and behavioral development, and supports learned odor associations necessary for infant attachment. Endogenous opioids are well characterized to mediate the calming and analgesic properties of maternal touch; yet their role in learned odor-touch associations is unknown. We administered naltrexone, an opioid receptor antagonist, before or immediately following classical conditioning with peppermint odor and tactile stimulation (stroking) in rat neonates. Results indicate odor-stroke conditioning produces odor preferences facilitated by endogenous opioids during acquisition and memory consolidation. These results provide additional evidence for the modulatory role of opioids in neonate learning and memory. Disturbances to this system may alter the impact of touch on infant development, particularly in the realm of learning necessary for attachment. ß 2005 Wiley Periodicals, Inc. Dev Psychobiol 48: 71-78, 2006.

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“…The stress-mitigating and rewarding effects that an infant experiences while interacting with its mother are thought to be mediated in part by release of the endogenous opioids (4,5), and work in rodents, dogs, and primates suggests that the diminution in endogenous opioid system activation during mother-infant separation is important in eliciting a distress vocalization response (6)(7)(8). In fact, it has been stated that separation distress may reflect a state of ''endorphin withdrawal'' (9).…”

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confidence: 99%

Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates

Barr

Schwandt

Lindell

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

178

151

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In a variety of species, development of attachment to a caregiver is crucial for infant survival and partly mediated by the endogenous opioids. Functional mu-opioid receptor gene polymorphisms are present in humans (OPRM1 A118G) and rhesus macaques (OPRM1 C77G). We hypothesized that rhesus infants carrying a gain-of-function OPRM1 77G allele would experience increased reward during maternal contact and would, therefore, display increased measures of attachment. We collected behavioral data from rhesus macaques (n ‫؍‬ 97) during early infancy and at 6 months of age, across four cycles of maternal separation (4 days) and reunion (3 days). Animals were genotyped for the OPRM1 C77G polymorphism, and the effects of this allele on attachmentrelated behaviors were analyzed. Infants carrying the G allele exhibited higher levels of attachment behavior during early infancy. During prolonged periods of maternal separation, although infant macaques homozygous for the C allele exhibited decreases in their levels of distress vocalization with repeated separation, this response persisted in G allele carriers. The OPRM1 77G allele also affected social preference during reunion. C/G infants spent increasing amounts of time in social contact with their mothers as a function of repeated separation and were less likely to interact with other individuals in the social group, a pattern not observed among infants with the C/C genotype. These findings suggest a role for OPRM1 variation in the expression of attachment behavior in human subjects, especially as a function of separation from the caregiver.genetic ͉ rhesus macaque ͉ mother-infant bond ͉ C77G ͉ A118G

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Opioid‐mediation of separation distress in 10‐day‐old rats: Reversal of stress with maternal stimuli

Cited by 220 publications

References 38 publications

Acquisition and expression of a socially mediated separation response

Acquisition and expression of a socially mediated separation response

Examining the role of endogenous opioids in learned odor–stroke associations in infant rats

Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates

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