Autoradiographic Evidence of Delta-Opioid Receptor Downregulation after Prenatal Stress in Offspring Rat Brain

Sánchez,; Milanés, M. Victoria; Pazos, Ángel; Díaz, Álvaro; Ml, Laorden

doi:10.1159/000028341

Cited by 16 publications

(8 citation statements)

References 29 publications

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“…It is not clear why a parallel decrease in opioid receptor expression was also noted. However, previous studies have similarly reported a long-term increase in endogenous opioid peptide along with a concomitant decrease in mu and delta opioid receptor density in the lateral hypothalamus of offspring following gestational stress (Sanchez et al, 1996, 2000). Alternatively, opioid receptors are rapidly internalized following ligand binding, which would also result in a concomitant decrease in opioid receptor availability.…”

Section: Discussionmentioning

confidence: 91%

Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal gray

LaPrairie

Murphy

2009

Front. Behav. Neurosci.

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Studies in both rodents and humans have shown that acute inflammatory pain experienced during the perinatal period produces long-term decreases in pain sensitivity (hypoalgesia) (Grunau et al., 1994a, 2001; Ren et al., 2004; LaPrairie and Murphy, 2007). To date, the mechanisms underlying these long-term adaptations, however, have yet to be elucidated. The present studies tested the hypothesis that neonatal inflammatory pain induces an upregulation in endogenous opioid tone that is maintained into adulthood, and that this increase in opioid tone provides the underlying mechanism for the observed hypoalgesia. On the day of birth (P0), inflammatory pain was induced in male and female Sprague-Dawley rats by intraplantar administration of carrageenan (CGN; 1%). In adulthood (P60), these animals displayed significantly increased paw withdrawal latencies in response to a noxious thermal stimulus in comparison to controls. Systemic administration of the brain-penetrant opioid receptor antagonist naloxone HCl, but not the peripherally restricted naloxone methiodide, significantly attenuated the injury-induced hypoalgesia. Direct administration of naloxone HCl or antagonists directed at the mu or delta opioid receptors into the midbrain periaqueductal gray (PAG) also significantly reversed the injury-induced hypoalgesia in adult rats. Parallel anatomical studies revealed that inflammatory pain experienced on the day of birth significantly increased beta-endorphin and met/leu-enkephalin protein levels and decreased opioid receptor expression in the PAG of the adult rat. Thus, early noxious insult produces long-lasting alterations in endogenous opioid tone, thereby profoundly impacting nociceptive responsiveness in adulthood.

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Section: Discussionmentioning

confidence: 91%

Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal gray

LaPrairie

Murphy

2009

Front. Behav. Neurosci.

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“…Glucocorticoid receptor density in the ventromedial prefrontal cortex (vmPFC) and limbic system, specifically the amygdala and hippocampus, has been proposed as a possible mechanism for environmental stress-cortisol-brain interactions relevant to psychopathology, as evinced in rodent research1112. Human work has further highlighted potential sensitivity in the amygdala-vmPFC pathway for emotional reactivity and recovery131415.…”

Section: Stress and Cortisolmentioning

confidence: 99%

Experience-Driven Differences in Childhood Cortisol Predict Affect-Relevant Brain Function and Coping in Adolescent Monozygotic Twins

Burghy

Fox

Cornejo

et al. 2016

Sci Rep

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Stress and emotion involve diverse developmental and individual differences. Partially attributed to the development of the prefrontal cortex (PFC), the amygdala, and hypothalamic-pituitary-adrenal axis, the precise genetic and experiential contributions remain unknown. In previous work, childhood basal cortisol function predicted adolescent resting-state functional connectivity (rs-FC) and psychopathology. To parse experience-driven (non-genetic) contributions, we investigated these relations with a monozygotic (MZ) twin design. Specifically, we examined whether intrapair differences in childhood afternoon cortisol levels predicted cotwin differences in adolescent brain function and coping. As expected, intrapair differences in childhood cortisol forecast amygdala-perigenual PFC rs-FC (R2 = 0.84, FWE-corrected p = 0.01), and amygdala recovery following unpleasant images (R2 = 0.40, FWE-corrected p < 0.05), such that the cotwin with higher childhood cortisol evinced relatively lower rs-FC and poorer amygdala recovery in adolescence. Cotwin differences in amygdala recovery also predicted coping styles. These data highlight experience-dependent change in childhood and adolescence.

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“…These include a decrease in foetal bendorphin, CRH (Ohkawa et al, 1988) and noradrenaline production (Ohkawa et al, 1991). In the adult offspring, there is a reduction in pro-opiomelanocortin mRNA expression in the hypothalamus (Weinstock et al, 1992), and a down-regulation of brain opioid receptors (Insel et al, 1990;Sanchez et al, 1996;. The PS rats also show a significant alteration in their analgesic response to morphine (Kinsley et al, 1988) and a decrease in the opioid component of their exploratory behaviour in a novel situation (Poltyrev and Weinstock, 1997).…”

Section: Effect Of Maternal Administration Of Naltrexone On Behaviourmentioning

confidence: 99%

“…These include an alteration in cerebral asymmetry Alonso et al, 1991b) that is consistent with the loss of left-sided cerebral dominance, and is observed in humans with abnormalities in development and with schizophrenia (Yeo et al, 1997;Satz and Green, 1999), heightened anxiety, as seen in the poorer coping skills in the presence of unknown or alarming circumstances (Meijer, 1985;Fride et al, 1985;1986) and behavioural and physiological symptoms of depression (Secoli and Teixeira, 1998;Koehl et al, 1999;Rao et al, 1999;Brown et al, 2000). Prenatal stress may also increase the propensity for alcohol and drug addiction (Huttunen and Niskanen 1978;Deminiere et al, 1992), through permanent alterations in limbic opioid, benzodiazepine (BDZ) and dopamine receptors (Fride et al, 1985;Insel et al, 1990;Alonso et al, 1994;Henry et al, 1995;Sanchez et al, 1996;. This, and the other behaviour anomalies induced by prenatal stress are associated with increased activity and impaired feedback regulation of the hypothalamic pituitary adrenal (HPA) axis (Weinstock et al, 1992;Henry et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Can the Behaviour Abnormalities Induced by Gestational Stress in Rats be Prevented or Reversed?

Weinstock

2002

Stress

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Gestational stress increases circulating maternal hormones that produce changes in behaviour and impair the feedback regulation of the hypothalamic pituitary adrenal axis of the offspring. Prenatally-stressed (PS) rats also release more corticotropin-releasing hormone (CRH) in the limbic system in response to stimulation than controls. This contributes to their exaggerated fear of intimidating situations and depressive-like behaviour. By using different treatments given to the pregnant mother, to neonatal or adult offspring, it has been possible to learn more about the mechanisms underlying the behavioural abnormalities induced by gestational stress. Many of these treatments were also able to prevent or reverse the abnormalities. They included maternal adrenalectomy and replacement of her basal hormone levels to avoid the prolonged elevation of plasma corticosterone, administration of anti-anxiety agents to reduce her reactions to the stress and continuous blockade of opioid receptors to prevent down-regulation of the foetal opioid system and subsequent alterations in behaviour. Hyperanxiety in the adult PS offspring could also be avoided if, as neonates, they were handled daily for 10 days, or given an antidepressant, amitriptyline for 4-5 weeks in the prepubertal period. Increased fear of novelty in adult PS rats could also be abolished by the intracerebro-ventricular administration of a CRH antagonist. This suggests that the new non-peptide CRH1 receptor antagonists that enter the brain might provide an effective treatment for the behaviour abnormalities in the offspring arising as a result of gestational stress.

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Autoradiographic Evidence of Delta-Opioid Receptor Downregulation after Prenatal Stress in Offspring Rat Brain

Cited by 16 publications

References 29 publications

Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal gray

Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal gray

Experience-Driven Differences in Childhood Cortisol Predict Affect-Relevant Brain Function and Coping in Adolescent Monozygotic Twins

Can the Behaviour Abnormalities Induced by Gestational Stress in Rats be Prevented or Reversed?

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