Effects of kindling on subsequent learning, memory, behavior, and seizure susceptibility.
To determine the long-term effects of seizures on the developing brain we kindled 20-, 40-, and 60-day-old rats to stage 5 seizures and then elicited an additional 15 seizures using the same kindling stimulation. At age 80 days, all animals that reached stage 5 kindling, and their respective age-matched controls, underwent behavioral testing using the Morris water maze, open field test, and handling test. Prior to euthanasia the animals had seizure threshold tested using flurothyl inhalation. No differences were noted in time to platform in the water maze or activity level in the open field test between the kindled rats and controls in any of the three age groups. Rats kindled at age 20 and 40 were more emotional than the controls in the handling test. In the flurothyl inhalation test, rats kindled at 40 and 60 days of age had a shorter latency to all seizures stages than the controls. These results demonstrate that while kindling results in no alteration of learning, memory, or activity level, it does result in altered emotionality and activity level in immature animals, as well as reduced seizure threshold in pubescent and mature rats. The animal model used appears to be an important variable in determining the long-term effects of seizures.
Holmes
G L
GL
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, MA 02115.
Chronopoulos
A
A
Stafstrom
C E
CE
Mikati
M A
MA
Thurber
S J
SJ
Hyde
P A
PA
Thompson
J L
JL
D000280:Administration, Inhalation; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001522:Behavior, Animal / Q000502:physiology*; D004198:Disease Susceptibility; D004558:Electric Stimulation; D005481:Flurothyl / Q000494:pharmacology; D006234:Handling, Psychological; D007608:Kainic Acid; D007696:Kindling, Neurologic; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology
D005481:Flurothyl; D007608:Kainic Acid