, Volume 103, Issue 3, pp 398–406 | Cite as

Long-term effects of neonatal exposure to isobutylmethylxanthine

II. Attenuation of acute morphine withdrawal in mature rats
  • Bethany S. Neal
  • Rita B. Messing
  • Sheldon B. Sparber
Original Investigations


An acute model of morphine withdrawal was used to determine if neonatal exposure to 3-isobutyl-1-methylxanthine (IBMX) would cause alterations in the expression of withdrawal in the adult rat. IBMX induces a quasi-morphine withdrawal syndrome (QMWS), which is almost identical to true morphine withdrawal both behaviorally and neurochemically. Transient IBMX treatment during infancy (on days 7–10 of life) caused an attenuated suppression of fixed ratio (FR) responding during acute morphine withdrawal in adulthood; however, there appeared to be no attenuation of withdrawal-induced hypothermia. The attenuated behavioral response was not due to an altered ability to express withdrawal, as these rats did not react differently to various doses of IBMX plus naloxone (i.e., varying severities of quasi-morphine withdrawal) in adulthood. Coad-ministration of the serotonin (5-HT) antagonist mianserin with IBMX in the neonate prevented the effects of IBMX. Both the mianserin-treated and the IBMX plus mianserin-treated groups had increased levels of [3H]naloxone binding in brainstem, while IBMX treatment alone apparently had no significant effect. None of the neonatal drug treatments affected [3H]naloxone binding in frontal cortex. Thus, the long-term effects of IBMX on the opioid withdrawal response cannot be explained by changes in the number of opioid binding sites (labelled with [3H]naloxone) within the brain. The results indicate that exposure to a methylxanthine, and thus quasi-morphine withdrawal, during development results in long-lasting alterations of a system which is involved in opioid withdrawal. Because coadministration of mianserin prevented the effects of IBMX, 5-HT and 5-HT2 receptors are implicated in these effects.

Key words

Isobutylmethylxanthine Development Mianserin Serotonin Morphine withdrawal 


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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Bethany S. Neal
    • 1
  • Rita B. Messing
    • 1
  • Sheldon B. Sparber
    • 1
  1. 1.Departments of Pharmacology and Psychiatry, Program in NeuroscienceUniversity of MinnesotaMinneapolisUSA

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