Fenfluramine effects on serotonergic measures in vervet monkeys.
Chronic fenfluramine treatment reduced whole blood serotonin and CSF 5-hydroxyindoleacetic acid, but increased aggressive and locomotor behavior, in adult male vervet monkeys (Cercopithecus aethiops sabaeus). Following a drug-free washout period to monitor the drug recovery course, we initiated a second period of fenfluramine treatment in the same animals. When whole blood serotonin concentrations were reduced by about 40% from predrug baseline levels, we examined 11 cortical and subcortical brain regions for their content of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, norepinephrine, and dopamine. We observed correspondence between the reduction in whole blood serotonin and the reduction in brain 5-hydroxytryptamine. Similarly, there was a correspondence between the reduced 5-hydroxyindoleacetic acid levels observed in CSF and brain. No alterations were noted in the concentrations of norepinephrine or dopamine. These observations suggest that the behavioral effects observed in monkeys after chronic fenfluramine treatment result from reduced central serotonin.
Nonhuman Primate Laboratory, Sepulveda Veterans Administration Medical Center, CA 91343.
G L
GL
Brammer
M J
MJ
Raleigh
E R
ER
Ritvo
E
E
Geller
M T
MT
McGuire
A
A
Yuwiler
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002522:Chlorocebus aethiops; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid / Q000378:metabolism; D012701:Serotonin / Q000097:blood / Q000502:physiology*
D018377:Neurotransmitter Agents; D005277:Fenfluramine; D012701:Serotonin