1. ¹Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Stockholm, Sweden
2. ²Department of Pharmacology, State University of New York, New York, NY, USA
3. ³Department of Pathology, State University of New York, New York, NY, USA
4. ⁴Department of Obstetrics and Gynecology, Maimonides Medical Center and SUNY Downstate Medical Center, Kings County Hospital, Brooklyn, NY, USA

Correspondence: Professor YL Hurd, Department of Clinical Neuroscience, Psychiatry Section, Karolinska University Hospital, Stockholm 17176, Sweden. E-mail: Yasmin.Hurd@cns.ki.se

Received 2 August 2005; Revised 5 December 2005; Accepted 21 December 2005; Published online 14 February 2006.

Abstract

Fetal development is a period sensitive to environmental influences such as maternal drug use. The most commonly used illicit drug by pregnant women is marijuana. The present study investigated the effects of in utero marijuana exposure on expression levels of opioid-related genes in the human fetal forebrain in light of the strong interaction between the cannabinoid and opioid systems. The study group consisted of 42 midgestation fetuses from saline-induced voluntary abortions. The opioid peptide precursors (preprodynorphin and preproenkephalin (PENK)) and receptor (mu, kappa and delta) mRNA expression were assessed in distinct brain regions. The effect of prenatal cannabis exposure was analyzed by multiple regression controlling for confounding variables (maternal alcohol and cigarette use, fetal age, sex, growth measure and post-mortem interval). Prenatal cannabis exposure was significantly associated with increased mu receptor expression in the amygdala, reduced kappa receptor mRNA in mediodorsal thalamic nucleus and reduced preproenkephalin expression in the caudal putamen. Prenatal alcohol exposure primarily influenced the kappa receptor mRNA with reduced levels in the amygdala, claustrum, putamen and insula cortex. No significant effect of prenatal nicotine exposure could be discerned in the present study group. These results indicate that maternal cannabis and alcohol exposure during pregnancy differentially impair opioid-related genes in distinct brain circuits that may have long-term effects on cognitive and emotional behaviors.