Post-natal morphine differentially affects opiate and stress analgesia in adult rats

Abstract

Alterations in nociceptive reactivity, opiate receptor binding, and other behavioral responses occur in rats exposed to morphine either in utero or post-natally. The present study examined whether post-natal morphine (0, 1 or 20 micrograms, days 1-7) altered analgesia on the tail-flick and jump tests induced by nonopioid-mediated continuous cold-water swims (CCWS), opioid-mediated intermittent cold-water swims (ICWS) or morphine (2.5 and 5.0 mg/kg, SC) in adult male and female rats. Changes in body weight, developmental signs (e.g., eye opening), basal pain thresholds, and both CCWS and ICWS hypothermia were also assessed. Previously-reported gender differences occurred for all forms of analgesia in control rats. Post-natal morphine treatment transiently increased ICWS analgesia and hypothermia, and transiently decreased CCWS analgesia and hypothermia, suggesting that these effects were not specific to pain inhibition. Post-natal morphine treatment significantly increased the magnitude of morphine analgesia on both tests in females, and significantly decreased the magnitude of morphine analgesia on both tests in males, thereby acting to vitiate the observed gender differences in morphine analgesia. Such effects could not be explained by concomitant changes in other measures. These data indicate that post-natal morphine treatment exerts highly selective effects upon specific analgesic responses which are gender sensitive.

Nociception and antinociception during the first week of life in mice: Sex differences and test dependence

“…It is worth noting that in this strain of mouse (CD-1), adult sex differences do not exist on either test of pain behavior, 30 although enhanced male sensitivity on the tail-withdrawal test 1,35 and enhanced female sensitivity on the hot-plate test 21,22 have both been observed in prior studies of adult laboratory rodents. The finding of enhanced morphine analgesia in male neonates compared to female is also consistent with most adulthood observations.…”

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

“…Postnatal morphine exposure decreases mu opioid receptor binding in the striatum, NAc, amygdala, hypothalamus, and spinal cord (Hammer et al, 1991;Kirby, 1983;Tempel, 1991). Perinatal morphine exposure also induces morphine tolerance (Chiang et al, 2010;Eriksson and Ronnback, 1989;Hovious and Peters, 1984), although an increased sensitivity to morphine analgesia has been reported in female offspring (Arjune and Bodnar, 1989). Aroyewun and Barr (1982) proposed that postnatal morphine also accelerates the maturation of some aspects of opiate-dependent behaviors, such as opiate antagonist-induced anorexia, that normally only occurs after P14.…”

Economical test methods for developmental neurobehavioral toxicity.

“…One of these studies has documented an interaction in rats between treatment and sex (that is, morphine hypersensitivity in males and hyposensitivity in females) with tests performed an extended period of time after the termination of morphine treatment on postnatal days 1 to 7. Moreover, the specificity of these effects was supported by the finding that both opioid stress analgesia after intermittent coldwater swims and nonopioid analgesia after continuous swims were little affected by the early treatment (70).…”

“…Without attempting a review of the literature on the effects of early treatments, it must be mentioned that several experiments have shown short-and long-term effects of prenatal and postnatal treatments with opiate drugs (particularly morphine and methadone) on pain reactivity and responses to analgesics, including opposite effects on sensitivity to morphine (68)(69)(70)(71). One of these studies has documented an interaction in rats between treatment and sex (that is, morphine hypersensitivity in males and hyposensitivity in females) with tests performed an extended period of time after the termination of morphine treatment on postnatal days 1 to 7.…”