Domoic acid: neurobehavioral and neurohistological effects of low-dose exposure in adult rats.
Adult rats treated IP with domoic acid at 0, 0.22, 0.65, or 1.32 mg/kg were tested for passive avoidance (PA), auditory startle (AS), or conditioned avoidance (CAR) behaviors. Clinical signs were observed only at the 1.32 mg/kg dose level. Within 24 h of dosing, rats surviving a dose of 1.32 mg/kg exhibited transient decreased body weight and exaggerated AS responding. Startle latency and habituation, PA, and CAR were not affected. Examination of brains from six rats per group revealed a subset (2/6) of animals receiving 1.32 mg/kg domoic acid with degenerating neurons in the hippocampal CA1/CA3 subregions and gliosis. The decreased body weight and increased startle suggest a hyperreactivity syndrome possibly related to neuronal degeneration in the hippocampus. In a separate experiment, domoic acid at an IP dose of 0.93 mg/kg was found to produce hypomotility in addition to a decrease in body weight. Both effects were reduced by pretreatment with scopolamine (2 mg/kg), but not with caffeine (30 mg/kg), indicating a possible cholinergic involvement in domoate's toxicity.
Sobotka
T J
TJ
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC 20204, USA. tjs@fdacf.ssw.dhhs.gov
Brown
R
R
Quander
D Y
DY
Jackson
R
R
Smith
M
M
Long
S A
SA
Barton
C N
CN
Rountree
R L
RL
Hall
S
S
Eilers
P
P
Johannessen
J N
JN
Scallet
A C
AC
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001362:Avoidance Learning / Q000187:drug effects*; D001835:Body Weight; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D006185:Habituation, Psychophysiologic; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*
D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid