Treatment of Pregnant Opioid Addicts with Buprenorphine. ?studies on animal models suggesting significant effects on central nervous system myelination of the offspring

SANCHEZ ES

Jornada; Developmental Neuroscience Lab-Presentations/Journal Club. Department of Anatomy and Neurobiology; 2006

To avoid street drug use and withdrawal symptoms, pregnant opioid addicts are treated with the opioid analogue buprenorphine. Unfortunately, this treatment is associated with increased risk of sudden infant death syndrome as well as child learning disabilities and behavioral problems. The underlying causes for these conditions are unclear; however, they may in part involve alterations in myelination since oligodendrocytes express opioid receptors in a developmentally regulated manner. To investigate this possibility, pregnant rats were implanted on day 7 of gestation with minipumps to deliver buprenorphine at 0.3-1 mg/kg/day, doses covering the range used in humans. Analysis of their pups at different postnatal ages (12-26 days) indicated that exposure to 0.3 mg/kg/day buprenorphine caused an accelerated and significant increase in the expression of all myelin basic protein (MBP) splicing variants in the brain. In contrast, treatment with the higher dose caused a developmental delay in MBPs expression. EM analysis of corpus callosum at 26-days of age, indicated that both buprenorphine doses cause changes in myelin thickness and the caliber and number of myelinated axons. Analysis of myelin associated glycoprotein (MAG) expression and glycosylation suggests that this molecule may play a crucial role in mediating these buprenorphine effects.  These results show for the first time that opioid signaling plays an important role in regulating myelination in vivo and provide cellular and molecular clues that may help to understand the neurological problems affecting children exposed to opioids in utero.