Postnatal behavior in hatano high- and low-avoidance rats following prenatal exposure to low-dose methylazoxymethanol.
The hypothesis that genetic factors influence behavioral effects was tested in rats exposed prenatally to methylazoxymethanol (MAM). We examined whether baseline behavior is an important factor influencing behavioral effects, and whether a behaviorally selected strain was useful for study of neurobehavioral teratology. Pregnant high- and low-avoidance animals (HAAs and LAAs) of the Hatano strain, selectively bred for high and low shuttlebox avoidance responses, respectively, were given an IP injection of a low dose of MAM (15 mg/kg) on day 14 of gestation. The offspring of these animals were subjected to behavioral tests for locomotor activity (running-wheel and open-field tests) and learning ability (Biel maze and shuttlebox avoidance tests). There were no significant effects of MAM on running-wheel activity or shuttlebox avoidance learning, whereas the number of errors in the Biel maze was increased in the MAM offspring of both strains. Interestingly, open-field activity of the MAM offspring was markedly decreased in LAAs but not in HAAs. Therefore, an additional experiment was performed to determine plasma levels of ACTH and corticosterone following open-field exposure. When compared to control offspring of the respective strains, plasma levels of ACTH and corticosterone were not altered by prenatal MAM treatment in LAAs. Instead, the MAM offspring in HAAs exhibited decreased ACTH levels in absence of behavioral alterations. These results demonstrated that prenatal exposure to low doses of MAM may alter postnatal behavior and endocrine response of the offspring, although to a differing degree in HAAs and LAAs. Our observations suggested that behaviorally selected strains are sensitive to neurobehavioral teratogens such as MAM.
Ohta
R
R
Laboratory of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, 257-8523, Hadano, Kanagawa, Japan.
Matsumoto
A
A
Sato
M
M
Shirota
M
M
Nagao
T
T
Tohei
A
A
Taya
K
K
D000311:Adrenal Glands / Q000033:anatomy & histology / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D004702:Endocrine Glands / Q000187:drug effects; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D008746:Methylazoxymethanol Acetate; D000324:Adrenocorticotropic Hormone; C030667:methylazoxymethanol; D003345:Corticosterone