TY - JOUR
T1 - Altered localization of choline transporter sites in the mouse hippocampus after prenatal heroin exposure
AU - Vatury, Ori
AU - Barg, Jacob
AU - Slotkin, Theodore A.
AU - Yanai, Joseph
PY - 2004/3/1
Y1 - 2004/3/1
N2 - 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 10 mg/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.
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 10 mg/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.
KW - Acetylcholine
KW - Autoradiography
KW - Choline transporter
KW - Hemicholinium-3
KW - Heroin
KW - Hippocampus
UR - http://www.scopus.com/inward/record.url?scp=2342452614&partnerID=8YFLogxK
U2 - 10.1016/j.brainresbull.2003.11.004
DO - 10.1016/j.brainresbull.2003.11.004
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C2 - 15121236
AN - SCOPUS:2342452614
SN - 0361-9230
VL - 63
SP - 25
EP - 32
JO - Brain Research Bulletin
JF - Brain Research Bulletin
IS - 1
ER -