title: Persisting behavioral consequences of prenatal domoic acid exposure in rats.
abstract: To investigate the behavioral effects of prenatal exposure to the marine toxin domoic acid, pregnant female rats were injected subcutaneously with 0, 0.3, 0.6, or 1.2 mg/kg of domoic acid on gestational day 13. The offspring were then run through a behavioral testing battery to determine the developmental effects of the toxin on spontaneous alternation in the T-maze, on locomotor activity in the Figure-8 maze, and on working memory in the 8-arm radial maze. In the T-maze, no significant domoic acid induced differences were seen on spontaneous alternation, but there were significant domoic acid effects on latency. Prenatal domoic acid exposure caused a dose-related increase in response latency in the second spontaneous alternation test. There was also a significant domoic acid effect seen in the 1-h long Figure-8 maze test. Locomotor activity measured in the Figure-8 maze detected a persisting effect of the 1.2 mg/kg domoic acid dose, which significantly increased the rate of habituation over the activity test session. This was characterized by higher initial activity followed by greater decline in activity. In the radial-arm maze the control vehicle treated rats showed the normal sex-related difference in spatial learning and memory with males outperforming females. Developmental domoic acid exposure decreased this effect such that the normal sex difference in spatial memory was not seen with the 1.2 mg/kg domoic acid dose. The rats of both sexes with a history of prenatal domoic acid exposure showed increased susceptibility to the amnestic effects of the muscarinic acetylcholine scopolamine, suggesting that they had less functional reserve with which to solve the radial-arm maze memory task. This study demonstrates persisting neurobehavioral effects of acute prenatal exposure to domoic acid at doses that do not cause overt clinical signs of toxicity.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3412 DUMC, Durham, NC, 27710, USA. edlevin@duke.edu
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
authors.forename: Kristen
authors.initials: K
authors.lastname: Pizarro
authors.forename: Wyki Gina
authors.initials: WG
authors.lastname: Pang
authors.forename: Jerry
authors.initials: J
authors.lastname: Harrison
authors.forename: John S
authors.initials: JS
authors.lastname: Ramsdell
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D012727:Sex Characteristics
chemical_list: D018727:Muscarinic Antagonists; D009498:Neurotoxins; D012601:Scopolamine; C012301:domoic acid; D007608:Kainic Acid