Chronic morphine exposure during puberty induces long-lasting changes in opioid-related mRNA expression in the mediobasal hypothalamus

Abstract

Substance abuse in developing females may have significant long-term effects on reproductive competency. Chronic morphine exposure during puberty has been shown to reduce prolactin secretion in lactating rats. Opioid activity within the mediobasal hypothalamus (MBH) regulates suckling-induced prolactin secretion. Thus, the current study was conducted to determine whether chronic pubertal morphine exposure alters the expression of mu- and/or kappa-opioid receptor mRNA or pro-opioimelanocortin (POMC) mRNA within the MBH. Using an increasing dose regimen, female Sprague-Dawley rats were injected twice daily for a total of 20 days with morphine sulfate or saline beginning at 30 days of age. Several weeks later, quantitative RT-PCR was used to determine mRNA expression within the MBH in diestrus, never pregnant (nulliparous) controls, postpartum day 5 (PPD5), PPD10, PPD18, and diestrus, reproductively experienced (primiparous) females. Pubertal morphine exposed females had increased mu- and kappa-receptor mRNA expression as well as decreased POMC mRNA expression on diestrus. During lactation, mu- and kappa-receptor mRNA expression in the MBH decreased while POMC mRNA expression increased in similarly treated females. No changes in mRNA expression were observed during lactation in pubertal saline-treated females; however, increased mu- and kappa-receptor mRNA expression as well as decreased POMC mRNA expression was observed in primiparous, pubertal saline-treated females when compared to nulliparous controls. Thus, chronic morphine exposure during puberty results in long-term alterations in mu- and kappa-receptor as well as POMC mRNA expression in the MBH which are similar to the changes observed following reproductive experience. These changes do not correlate with the decreased prolactin secretion observed during early lactation; however, they do demonstrate the enduring nature of the effects of chronic opiate exposure during puberty on hypothalamic opioid systems in adulthood.