Early post-natal administration of 5,7-dihydroxytryptamine destroys 5-HT neurons but does not affect spatial memory.
The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) may play an important role in learning and memory. It has also been suggested that 5-HT abnormalities may mediate some aspects of the cognitive disorders associated with Korsakoff syndrome and Alzheimer's Disease. The effect of intracisternally applied 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) on learning and memory in rodents was evaluated. Three-day-old rat pups were treated with pargyline (40 mg/kg, i.p.) followed by 5,7-DHT (50 micrograms/pup) and returned to the dam for a month. At 75 days of age, rats were tested on a learning set problem in the Morris water maze for 5 days followed by 30 days of testing in a 12-arm radial maze with 8 of the 12 arms baited. In the Morris water maze, the latency to locate the hidden platform did not differ significantly for 5,7-DHT treated and control rats (F less than 1.0). Similarly, 5,7-DHT treated rats performed comparably to controls on the 12-arm radial maze (F less than 1.0). At 106 days of age the assay of tryptophan hydroxylase activity in the dorsal raphe nuclei and hippocampus showed marked reduction (86%, 78%, respectively) in 5,7-DHT treated animals compared to vehicle injected controls. Immunocytochemical analysis was consistent with the biochemical results. In 5,7-DHT treated animals there was severe loss of neurons that bind 5-HT antibody in the dorsal and medial raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)
Volpe
B T
BT
Cornell University Medical College, Department of Neurology and Neuroscience, Burke Institute for Medical Research, New York, NY 10605.
Hendrix
C S
CS
Park
D H
DH
Towle
A C
AC
Davis
H P
HP
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D013028:Space Perception / Q000187:drug effects*; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D014365:Tryptophan Hydroxylase