PMID- 11248144
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20190513
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 60
IP  - 2
DP  - 2001 Apr
TI  - Neurotoxicological outcomes of perinatal heptachlor exposure in the rat.
PG  - 315-26
AB  - The developing nervous system has been identified as a potential target of 
      pesticide exposure. Heptachlor is a cyclodiene pesticide that was widely used for 
      many years, and for which inadvertent exposure to children and fetuses took place 
      in the early 1980s; yet little is known regarding the developmental neurotoxicity 
      of it and other cyclodienes. The aim of this study was to determine whether 
      perinatal heptachlor exposure results in persistent alterations in nervous system 
      function. Pregnant Sprague-Dawley dams were dosed from gestational day (GD) 12 to 
      postnatal day (PND) 7, whereupon the rat pups were dosed directly until PND 21 
      (group A) or PND 42 (group B). Dose levels were 0, 0.03, 0.3, or 3 mg/kg/day, po. 
      There were no dose-related effects on maternal weight, litter size, or pup 
      growth. GABA(A) receptor binding (using [(35)S] 
      tert-butylbicyclophosphorothionate; TBPS) and GABA-stimulated Cl- flux were 
      evaluated in control and high-dose brain tissues taken on PND 7, 21, and 43. The 
      B(max) values for [(35)S]-TBPS binding in brainstem, but not cortex, were 
      decreased in female rats across all ages tested. There were no such changes in 
      male rats, nor were K(D) values altered in either tissue or gender. 
      GABA-stimulated Cl- flux was decreased in female cortex synaptoneurosomes only on 
      PND 21. The ontogeny of the righting response (PND 2-5) was delayed in the 
      high-dose females. All subsequent testing took place a week to months after 
      dosing ceased. The functional observational battery (FOB) showed 
      treatment-related, but not necessarily dose-related, changes in different aspects 
      of the rat's reactivity and activity levels. Group-A rats also showed altered 
      within-session habituation of motor activity. There were no heptachlor-related 
      differences in motor activity following challenge with a range of 
      chlordiazepoxide doses. Cognitive assessments were conducted in both groups of 
      rats. There were no statistically significant differences among treatment groups 
      in a one-trial passive avoidance test, although there was a trend toward less 
      learning. In group B, rats (both sexes), heptachlor altered spatial learning in 
      the Morris water maze during two weeks of daily training (2 trials/day). On probe 
      trials, heptachlor-treated rats did not show significant preference for the 
      correct quadrant (all dose groups in males, high dose in females). These rats did 
      not show alterations on subsequent working-memory training (where the platform 
      position was relearned each day). Thus, perinatal exposure to heptachlor produced 
      neurochemical and persistent neurobehavioral changes, including alterations in 
      spatial learning and memory.
FAU - Moser, V C
AU  - Moser VC
AD  - Neurotoxicology Division, National Health and Environmental Effects Research 
      Laboratory, Office of Research and Development, U.S. EPA, Research Triangle Park, 
      North Carolina 27711, USA. moser.ginger@epa.gov
FAU - Shafer, T J
AU  - Shafer TJ
FAU - Ward, T R
AU  - Ward TR
FAU - Meacham, C A
AU  - Meacham CA
FAU - Harris, M W
AU  - Harris MW
FAU - Chapin, R E
AU  - Chapin RE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Chlorides)
RN  - 0 (Insecticides)
RN  - 0 (Receptors, GABA)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 7GLS9ACN3L (Heptachlor)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Behavior, Animal/*drug effects
MH  - Body Weight/drug effects
MH  - Brain/*drug effects/embryology/physiopathology
MH  - Brain Chemistry
MH  - Chlorides/metabolism
MH  - Embryonic and Fetal Development/*drug effects
MH  - Female
MH  - Heptachlor/pharmacokinetics/*toxicity
MH  - Insecticides/pharmacokinetics/*toxicity
MH  - Litter Size/drug effects
MH  - Male
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA/metabolism
MH  - Tissue Distribution
MH  - Toxicity Tests
MH  - gamma-Aminobutyric Acid/pharmacology
EDAT- 2001/03/15 10:00
MHDA- 2001/06/19 10:01
CRDT- 2001/03/15 10:00
PHST- 2001/03/15 10:00 [pubmed]
PHST- 2001/06/19 10:01 [medline]
PHST- 2001/03/15 10:00 [entrez]
AID - 10.1093/toxsci/60.2.315 [doi]
PST - ppublish
SO  - Toxicol Sci. 2001 Apr;60(2):315-26. doi: 10.1093/toxsci/60.2.315.