Transgenerational consequences of prepregnancy chronic morphine use on spatial learning and hippocampal Mecp2 and Hdac2 expression.

Abstract

There has recently been increasing interest in the transgenerational effects of opioids. Herein, transgenerational consequences of maternal chronic morphine consumption before gestation were investigated at the behavioral and molecular levels of next two generations. Twelve female Wistar rats were randomly divided into two groups: pregestation morphine-consuming and control mothers. Morphine-consuming mothers had access to morphine solution ad libitum for 2 months, whereas the control mothers received only tap water. One month after stopping morphine consumption, rats were mated. After parturition, male and female offspring and later grandoffspring of morphine-consuming and control mothers were divided and used as the study groups. Behavioral testing comprised spatial memory assessment using Morris water maze. Hippocampal expressions of Mecp2 and Hdac2 were investigated through real-time PCR. Spatial memory was significantly diminished in male but not female offspring and grandoffspring of morphine-consuming mothers versus control (P<0.01). Hippocampal Mecp2 and Hdac2 were significantly upregulated in male but not in female offspring and grandoffspring of morphine-consuming mothers compared with control (P<0.05). Consequences of prepregnancy morphine consumption have sex differences and are detectable at the behavioral and molecular level over at least the next two generations.