PMID- 15121236 OWN - NLM STAT- MEDLINE DCOM- 20040706 LR - 20131121 IS - 0361-9230 (Print) IS - 0361-9230 (Linking) VI - 63 IP - 1 DP - 2004 Mar 1 TI - Altered localization of choline transporter sites in the mouse hippocampus after prenatal heroin exposure. PG - 25-32 AB - Prenatal heroin exposure disrupts hippocampal cholinergic synaptic function and related behaviors. Biochemical studies indicate an increase in the number of presynaptic high-affinity choline transporter (HACT) sites, as assessed by [3H]hemicholinium-3 (HC-3) binding. The present study was designed to assess whether this effect involves global upregulation of the transporter, or whether disruption occurs with a specific tempero-spatial distribution. Pregnant mice were given 10mg/kg per day of heroin subcutaneously on gestational days (GD) 9-18. Autoradiographic distribution of HC-3 binding sites was evaluated in the hippocampus of the offspring at postnatal days 15, 25, and 53. These results, suggestive of hippocampal "miswiring," are likely to explain the net impairment of cholinergic synaptic function after prenatal heroin exposure, despite the simultaneous upregulation of both presynaptic cholinergic activity and postsynaptic receptors. Understanding the subregional selectivity of hippocampal defects can lead to the development of strategies that may potentially enable therapeutic interventions to offset or reverse the neurobehavioral defects. FAU - Vatury, Ori AU - Vatury O AD - The Ross Laboratory for Studies in Neural Birth Defects, Department of Anatomy and Cell Biology, The Hebrew University-Hadassah Medical School, Box 12272, 91120 Jerusalem, Israel. FAU - Barg, Jacob AU - Barg J FAU - Slotkin, Theodore A AU - Slotkin TA FAU - Yanai, Joseph AU - Yanai J LA - eng PT - Journal Article PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Membrane Transport Proteins) RN - 0 (choline transporter) RN - 312-45-8 (Hemicholinium 3) RN - 70D95007SX (Heroin) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/metabolism MH - Animals MH - Binding, Competitive/drug effects/physiology MH - Female MH - Hemicholinium 3/metabolism/pharmacokinetics MH - Heroin/*pharmacology MH - Heroin Dependence/*metabolism/physiopathology MH - Hippocampus/*drug effects/growth & development/metabolism MH - Male MH - Membrane Transport Proteins/*drug effects/metabolism MH - Mice MH - Neural Pathways/drug effects/physiopathology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Presynaptic Terminals/drug effects/metabolism MH - Radioligand Assay MH - Synaptic Membranes/drug effects/metabolism MH - Synaptic Transmission/*drug effects/physiology EDAT- 2004/05/04 05:00 MHDA- 2004/07/09 05:00 CRDT- 2004/05/04 05:00 PHST- 2003/09/07 00:00 [received] PHST- 2003/11/15 00:00 [revised] PHST- 2003/11/30 00:00 [accepted] PHST- 2004/05/04 05:00 [pubmed] PHST- 2004/07/09 05:00 [medline] PHST- 2004/05/04 05:00 [entrez] AID - S036192300300323X [pii] AID - 10.1016/j.brainresbull.2003.11.004 [doi] PST - ppublish SO - Brain Res Bull. 2004 Mar 1;63(1):25-32. doi: 10.1016/j.brainresbull.2003.11.004.