Is a serotonergic mechanism involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced appetite suppression in the Sprague-Dawley rat?
The major cause of TCDD-induced death in rats is a progressive voluntary feed refusal which has been correlated with reduced gluconeogenesis. Since centrally administered TCDD does not cause death or decreased feed intake in rats, the ability of TCDD to suppress appetite via peripheral mechanisms acting on the central nervous system was examined in two experimental models. First, it was found that the feed intake of rats on scheduled feeding cycles was not decreased by blood transfused from rats with TCDD-induced appetite suppression (8 days after a lethal dose of TCDD, i.p.). In contrast, a similar transfusion from normal, satiated rats did reduce feed intake of recipient rats by approximately 40%, suggesting that TCDD-treated rats are not satiated but rather that they are not hungry. In the second study tryptophan (the amino acid precursor of the neurotransmitter serotonin) was measured in the plasma and tryptophan, serotonin, norepinephrine and dopamine in the hypothalamus as well as dopamine and its metabolites in the striatum 4, 8, and 16 days after TCDD dosage (125 micrograms/kg, i.p.). Progressive time-dependent increases in tryptophan levels in plasma and brain were paralleled by increases in brain serotonin and 5-hydroxyindoleacetic acid (the primary metabolite of serotonin) in TCDD-treated rats. No changes were observed regarding the other biogenic amines. It is suggested based on these data and on substantial evidence from the published literature that a serotonergic mechanism may be involved in TCDD-induced feed intake reduction.
Rozman
K
K
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Pfeifer
B
B
Kerecsen
L
L
Alper
R H
RH
D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001803:Blood Transfusion; D002395:Catecholamines / Q000032:analysis; D003345:Corticosterone / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000502:physiology*; D014364:Tryptophan / Q000032:analysis
D002395:Catecholamines; D000072317:Polychlorinated Dibenzodioxins; D012701:Serotonin; D014364:Tryptophan; D003345:Corticosterone