Altered localization of choline transporter sites in the mouse hippocampus after prenatal heroin exposure

Brain Res Bull. 2004 Mar 1;63(1):25-32. doi: 10.1016/j.brainresbull.2003.11.004.


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.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Female
  • Hemicholinium 3 / metabolism
  • Hemicholinium 3 / pharmacokinetics
  • Heroin / pharmacology*
  • Heroin Dependence / metabolism*
  • Heroin Dependence / physiopathology
  • Hippocampus / drug effects*
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Male
  • Membrane Transport Proteins / drug effects*
  • Membrane Transport Proteins / metabolism
  • Mice
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Radioligand Assay
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology


  • Membrane Transport Proteins
  • choline transporter
  • Hemicholinium 3
  • Heroin
  • Acetylcholine