Altered localization of choline transporter sites in the mouse hippocampus after prenatal heroin exposure.
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.
Vatury
Ori
O
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.
Barg
Jacob
J
Slotkin
Theodore A
TA
Yanai
Joseph
J
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D005260:Female; D006426:Hemicholinium 3 / Q000378:metabolism / Q000493:pharmacokinetics; D003932:Heroin / Q000494:pharmacology*; D006556:Heroin Dependence / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D026901:Membrane Transport Proteins; C065637:choline transporter; D006426:Hemicholinium 3; D003932:Heroin; D000109:Acetylcholine