Prenatal phencyclidine exposure alters hippocampal cell proliferation in offspring rats

• Published in: Synapse (New York, N.Y.) Vol. 63; no. 9; pp. 729 - 736
• Main Authors: Tanimura, Atsushi, Liu, Juan, Namba, Takashi, Seki, Tatsunori, Matsubara, Yoichiro, Itoh, Masanobu, Suzuki, Toshihito, Arai, Heii
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2009
• Subjects: Animals; Animals, Newborn; Behavior, Animal - drug effects; Behavior, Animal - physiology; Bromodeoxyuridine; Cell Count; Cell Proliferation - drug effects; CNS development; Dentate Gyrus - drug effects; Dentate Gyrus - pathology; Dentate Gyrus - physiopathology; Disease Models, Animal; drug abuse; Excitatory Amino Acid Antagonists - toxicity; Female; hippocampal neurogenesis; Hippocampus - drug effects; Hippocampus - pathology; Hippocampus - physiopathology; Male; Memory Disorders - chemically induced; Memory Disorders - pathology; Memory Disorders - physiopathology; Motor Activity - drug effects; Motor Activity - physiology; neonatal rats; Neurogenesis - drug effects; Neurogenesis - physiology; phencyclidine; Phencyclidine - toxicity; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - pathology; Prenatal Exposure Delayed Effects - physiopathology; prenatal stress; Rats; Rats, Sprague-Dawley
• ISSN: 0887-4476; 1098-2396; 1098-2396
• DOI: 10.1002/syn.20660

Multiple case reports have described pregnancy in phencyclidine hydrochloride (PCP) abusers. Characteristic clinical symptoms of PCP‐exposed infants have revealed neurobehavioral or physical abnormalities. We designed this study to evaluate whether chronic prenatal exposure to PCP during the last 2 weeks of gestation in rats produces alterations of hippocampal neurogenesis in offspring. Rats received repeated subcutaneous injection of PCP (5 mg/kg) once daily during the last 2 weeks of gestation. Control animals received subcutaneous injection of physiological saline during gestation. Dams receiving repeated PCP administrations showed markedly increased locomotor activities on days 1, 5, and 10 during the last 2 weeks of gestation. At 21 days after birth, 5‐bromo‐2′‐deoxyuridine (BrdU)‐positive cells of offspring were counted in the granule cell layer (GCL) and subgranular zone of the dentate gyrus. The numbers of BrdU‐positive cells in the GCL in male and female offspring of the PCP‐treated group were significantly increased by ∼77% compared with those from the control group. At 56 days, the number of surviving BrdU‐positive cells also remained to be increased by 74% in the GCL in PCP‐treated group. At 21 days, locomotor activities of offspring in the PCP‐treated group were significantly decreased by ∼30% compared with those in the control group. However, neuronal differentiation of newly formed cells and cell survival were not influenced at 5 weeks after BrdU injections. Some altered biochemical or physiological conditions of offspring from dams receiving repeated PCP injections during pregnancy could influence changes in cell proliferation in the GCL of offspring during early development. Changes to cell proliferation in the hippocampus may affect behavioral abnormalities during infancy in offspring. Synapse 63:729–736, 2009. © 2009 Wiley‐Liss, Inc.