Maternal Cannabinoid Use Alters Cannabinoid (CB1) and Endothelin (ETB) Receptor Expression in the Brains of Dams but Not Their Offspring

Abstract

According to the 2015 National Survey on Drug Use and Health, cannabis (marijuana) is the most commonly used recreational drug in the US. Among pregnant women aged 14-55 years, 3.4% were cannabis users. Presently, little is known about the neurodevelopmental effect of cannabis use during pregnancy and/or nursing on neonates. Endothelin (ET) is essential for normal development of the central nervous system (CNS). Decreases in ETB receptor expression correlate with a decline in nerve growth factor (NGF) and an increase in vascular endothelial growth factor (VEGF) in postnatal brain. Activation of ETB and cannabinoid 1 (CB1) receptors each promote neurogenesis and enhance angiogenesis, indicating that both ET and CB systems play a critical role during early CNS development. Hence the purpose of this study was to determine whether maternal CB abuse during pregnancy and lactation alters the expression of ETB receptors, CB1 receptors, VEGF, and NGF in the postnatal rat brain. Sixteen pregnant Sprague-Dawley rats were administered either saline or anandamide (AEA) at a dose of 3 mg/kg/day i.p. from gestational day 7 and continued through weaning on postnatal day (PND) 21. Rat pups were subdivided into 4 subgroups and sacrificed on PND 2, 7, 14, and 28. Brain tissue of the pups and dams (sacrificed on PND 21) was analyzed via Western blot for the expression of ETB receptors, CB1 receptors, VEGF, and NGF. AEA-exposed dams had significantly fewer live births (p = 0.027), and their pups presented with significantly lower body weights on PND 7 (p = 0.013) and PND 28 (p = 0.018). There was no significant difference noted in ETB receptor, CB1 receptor, NGF, or VEGF expression in the pup brains. In all pups, brain ETB receptor expression decreased and CB1 receptor expression increased with age. In the AEA-exposed dam brain, however, there was a decrease in ETB receptor (p = 0.043) and an increase in CB1 receptor expression (p = 0.033). AEA exposure during pregnancy appears to affect fetal viability and postnatal weight gain in offspring while not altering the expression patterns of ETB receptors, CB1 receptors, NGF, or VEGF in the pup brain. The observed trend to an increase in CB1 receptor expression concurrent with a decrease in ETB receptor expression in both dams and pups may point to a homeostatic regulation between these 2 systems in CNS development and neuroprotection.