PMID- 12460655
OWN - NLM
STAT- MEDLINE
DCOM- 20030312
LR  - 20190922
IS  - 0892-0362 (Print)
IS  - 0892-0362 (Linking)
VI  - 24
IP  - 6
DP  - 2002 Nov-Dec
TI  - Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.
PG  - 733-41
AB  - Use of chlorpyrifos (CPF) has been curtailed due to its developmental 
      neurotoxicity. In rats, postnatal CPF administration produces lasting changes in 
      cognitive performance, but less information is available about the effects of 
      prenatal exposure. We administered CPF to pregnant rats on gestational days (GD) 
      17-20, a peak period of neurogenesis, using doses (1 or 5 mg/kg/day) below the 
      threshold for fetal growth impairment. We then evaluated performance in the 
      T-maze, Figure-8 apparatus and 16-arm radial maze, beginning in adolescence and 
      continuing into adulthood. CPF elicited initial locomotor hyperactivity in the 
      T-maze. Females showed slower habituation in the Fig. 8 maze; no effects were 
      seen in males. In the radial-arm maze, females showed impaired choice accuracy 
      for both working and reference memory and again, males were unaffected. Despite 
      the deficits, all animals eventually learned the maze with continued training. At 
      that point, we challenged them with the muscarinic antagonist, scopolamine, to 
      determine the dependence of behavioral performance on cholinergic function. 
      Whereas control females showed impairment with scopolamine, CPF-exposed females 
      did not, implying that the delayed acquisition of the task had been accomplished 
      through alternative mechanisms. The differences were specific to muscarinic 
      circuits, as control and CPF groups responded similarly to the nicotinic 
      antagonist, mecamylamine. Surprisingly, adverse effects of CPF were greater in 
      the group receiving 1 mg/kg as compared to 5 mg/kg. Promotional effects of 
      acetylcholine (ACh) on cell differentiation may thus help to offset CPF-induced 
      developmental damage that occurs through other noncholinergic mechanisms. Our 
      results indicate that late prenatal exposure to CPF induces long-term changes in 
      cognitive performance that are distinctly gender-selective. Additional defects 
      may be revealed by similar strategies that subject the animals to acute 
      challenges, thus, uncovering the adaptive mechanisms that maintain basal 
      performance.
FAU - Levin, Edward D
AU  - Levin ED
AD  - Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 
      Durham, NC 27710, USA. edlevin@duke.edu
FAU - Addy, Nii
AU  - Addy N
FAU - Baruah, Avanti
AU  - Baruah A
FAU - Elias, Alana
AU  - Elias A
FAU - Christopher, N Channelle
AU  - Christopher NC
FAU - Seidler, Frederic J
AU  - Seidler FJ
FAU - Slotkin, Theodore A
AU  - Slotkin TA
LA  - eng
GR  - ES10356/ES/NIEHS NIH HHS/United States
GR  - ES10387/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Receptors, Muscarinic)
RN  - DL48G20X8X (Scopolamine)
RN  - JCS58I644W (Chlorpyrifos)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/drug effects/physiopathology
MH  - Chlorpyrifos/*toxicity
MH  - Cholinergic Fibers/drug effects/physiology
MH  - Cholinesterase Inhibitors/*toxicity
MH  - Cognition Disorders/*chemically induced/physiopathology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Male
MH  - Maze Learning/*drug effects/physiology
MH  - Memory, Short-Term/drug effects/physiology
MH  - Mental Disorders/*chemically induced/physiopathology
MH  - Motor Activity/*drug effects/physiology
MH  - Muscarinic Antagonists/pharmacology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reaction Time/drug effects/physiology
MH  - Receptors, Muscarinic/drug effects/metabolism
MH  - Scopolamine/pharmacology
MH  - Sex Characteristics
EDAT- 2002/12/04 04:00
MHDA- 2003/03/13 04:00
CRDT- 2002/12/04 04:00
PHST- 2002/12/04 04:00 [pubmed]
PHST- 2003/03/13 04:00 [medline]
PHST- 2002/12/04 04:00 [entrez]
AID - S0892036202002726 [pii]
AID - 10.1016/s0892-0362(02)00272-6 [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 2002 Nov-Dec;24(6):733-41. doi: 
      10.1016/s0892-0362(02)00272-6.