PMID- 16079074
OWN - NLM
STAT- MEDLINE
DCOM- 20060217
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 113
IP  - 8
DP  - 2005 Aug
TI  - Alterations in central nervous system serotonergic and dopaminergic synaptic 
      activity in adulthood after prenatal or neonatal chlorpyrifos exposure.
PG  - 1027-31
AB  - Exposure to chlorpyrifos (CPF) alters neuronal development of serotonin (5HT) and 
      dopamine systems, and we recently found long-term alterations in behaviors 
      related to 5HT function. To characterize the synaptic mechanisms underlying these 
      effects, we exposed developing rats to CPF regimens below the threshold for 
      systemic toxicity, in three treatment windows: gestational days (GD) 17-20, 
      postnatal days (PN) 1-4, or PN11-14. In early adulthood (PN60), we assessed basal 
      neurotransmitter content and synaptic activity (turnover) in brain regions 
      containing the major 5HT and dopamine projections. CPF exposure on GD17-20 or 
      PN1-4 evoked long-term increases in 5HT turnover across multiple regions; the 
      effects were not secondary to changes in neurotransmitter content, which was 
      unaffected or even decreased. When the treatment window was shifted to PN11-14, 
      there were no long-term effects. Dopamine turnover also showed significant 
      increases after CPF exposure on GD17-20, but only when the dose was raised above 
      the threshold for overt toxicity; however, hippocampal dopamine content was 
      profoundly subnormal after exposures below or above the acute, toxic threshold, 
      suggesting outright neurotoxicity. These results indicate that, in a critical 
      developmental period, apparently nontoxic exposures to CPF produce lasting 
      activation of 5HT systems in association with 5HT-associated behavioral 
      anomalies.
FAU - Aldridge, Justin E
AU  - Aldridge JE
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, North Carolina 27710, USA.
FAU - Meyer, Armando
AU  - Meyer A
FAU - Seidler, Frederic J
AU  - Seidler FJ
FAU - Slotkin, Theodore A
AU  - Slotkin TA
LA  - eng
GR  - R01 ES010387/ES/NIEHS NIH HHS/United States
GR  - ES10356/ES/NIEHS NIH HHS/United States
GR  - P42 ES010356/ES/NIEHS NIH HHS/United States
GR  - T32 ES007031/ES/NIEHS NIH HHS/United States
GR  - ES07031/ES/NIEHS NIH HHS/United States
GR  - ES10387/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Insecticides)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 333DO1RDJY (Serotonin)
RN  - JCS58I644W (Chlorpyrifos)
RN  - VTD58H1Z2X (Dopamine)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/*drug effects/metabolism
MH  - Chlorpyrifos/*toxicity
MH  - Dopamine/metabolism
MH  - Female
MH  - Homovanillic Acid/metabolism
MH  - Insecticides/*toxicity
MH  - Male
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Synaptic Transmission/drug effects
PMC - PMC1280344
EDAT- 2005/08/05 09:00
MHDA- 2006/02/18 09:00
PMCR- 2005/08/01
CRDT- 2005/08/05 09:00
PHST- 2005/08/05 09:00 [pubmed]
PHST- 2006/02/18 09:00 [medline]
PHST- 2005/08/05 09:00 [entrez]
PHST- 2005/08/01 00:00 [pmc-release]
AID - ehp0113-001027 [pii]
AID - 10.1289/ehp.7968 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2005 Aug;113(8):1027-31. doi: 10.1289/ehp.7968.