Changes in prodynorphin and POMC gene expression in several brain regions of rat fetuses prenatally exposed to Δ9-tetrahydrocannabinol

Abstract

Recently, we demonstrated that prenatal Δ9-tetrahydrocannabinol (Δ9-THC) exposure alters proenkephalin mRNA levels in several brain regions of rat fetuses. In the present study, we analyzed mRNA levels of the two other opioid peptide precursors, prodynorphin and proopiomelanocortin (POMC), in several brain nuclei of rat fetuses which were exposed daily to Δ9-THC from day 5 of gestation. Prenatal Δ9-THC exposure altered POMC and prodynorphin mRNA levels in most of the brain areas studied at different fetal ages, but the effects were sex-dependent. Thus, POMC mRNA levels increased in Δ9-THC-exposed females, but decreased in Δ9-THC-exposed males at GD21 in the arcuate nucleus, cerebral cortex and habenular nuclei. POMC mRNA levels also increased in the arcuate nucleus and cerebral cortex of Δ9-THC-exposed fetuses at GD18. Prodynorphin mRNA levels were not altered by the prenatal Δ9-THC exposure in the striatum, cerebral cortex, hippocampus and hypothalamic structures of fetuses at GD16 and GD18, but a sexually dimorphic response was observed at GD21. Thus, prodynorphin mRNA levels increased in the cerebral cortex, hippocampus and paraventricular hypothalamic nucleus of Δ9-THC-exposed females, whereas no changes were observed in Δ9-THC-exposed males. In summary, Δ9-THC exposure altered the prenatal development of POMC and prodynorphin mRNA levels in several brain structures. Changes in POMC were similar to those reported previously for proenkephalin, increases in females but decreases in males, whereas changes in prodynorphin were only observed in females.