Persistent neurobehavioral effects of early postnatal domoic acid exposure in rats.
Domoic acid (DA) is a marine biotoxin, produced by the diatom Pseudo-nitzchia spp., which has been shown to cause cognitive impairment in adults who are exposed via contaminated seafood. The neurobehavioral consequences of developmental exposure are much less well understood. In a previous study, we showed that a single prenatal exposure to DA in rats at mid-gestation caused neurobehavioral changes that persist into adulthood including increased susceptibility to the benchmark amnestic drug scopolamine. In the current study, we examined the lasting neurobehavioral consequences of DA exposure on the first day of postnatal life, a time in rats marking the completion of the major phase of neuroproliferation and corresponding to week 24 of human gestation. The effects of DA exposure at doses from 0.025-0.1 mg/kg (s.c.) twice per day on each of postnatal days 1 and 2 were compared with vehicle-treated controls and rats treated by the same protocol with 1 mg/kg of kainic acid. Following kainic acid exposure, a sex-selective effect was seen with females but not males showing a significant slowing of response latency in the radial-arm maze. The high DA dose of 0.1 mg/kg was quite toxic causing lethality in all of the offspring exposed and this group was excluded from further analysis. When the offspring in the 0.05 mg/kg DA dose group were tested, significant hypoactivity in the Figure-8 maze was observed during adolescence. No significant DA effects were seen in response latency or choice accuracy on the radial-arm maze during either acquisition or with challenge of the amnestic drug scopolamine. Early postnatal DA exposure in the rat can be lethal and sublethal exposure can cause neurobehavioral effects manifest in modest hypoactivity during the adolescent period. However, the sublethal persistent neurobehavioral toxicity appears to be less pervasive than reported effects following DA administered mid-gestation.
Levin
Edward D
ED
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
Pang
Wyki Gina
WG
Harrison
Jerry
J
Williams
Paul
P
Petro
Ann
A
Ramsdell
John S
JS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D003627:Data Interpretation, Statistical; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000633:toxicity; D009467:Neuromuscular Depolarizing Agents / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D010775:Photic Stimulation; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000633:toxicity
D018690:Excitatory Amino Acid Agonists; D018727:Muscarinic Antagonists; D009467:Neuromuscular Depolarizing Agents; D012601:Scopolamine; C012301:domoic acid; D007608:Kainic Acid