Fluoxetine-induced changes in body weight and 5-HT1A receptor-mediated hormone secretion in rats on a tryptophan-deficient diet.
Tryptophan depleting protocols are commonly used to study the role of serotonin in mood disorders. The present study examined the impact of a tryptophan-deficient diet and fluoxetine on the serotonergic regulation of neuroendocrine function and body weight. We hypothesized that the regulation of postsynaptic 5-HT1A receptors is dependent on the levels of 5-HT in the synapse. Rats on a control or a tryptophan-deficient diet received daily injections of saline or fluoxetine (5 or 10 mg.kg-1.day-1 ip) from day 7 to day 21. The tryptophan-deficient diet produced a 41% reduction in the level of 5-HT but no change in the density of [3H]paroxetine-labeled 5-HT transporters. Treatment with fluoxetine inhibited the gain in weight in rats maintained on the control diet. The tryptophan-deficient diet produced a significant loss in body weight that was not significantly altered by treatment with fluoxetine. Treatment with fluoxetine produced a dose-dependent desensitization of hormone responses to injection of the 5-HT1A receptor agonist (+/-)8-hydroxy-2-(di-n-propylamino)tetralin ((+/-)8-OH-DPAT). The tryptophan-deficient diet produced an increase in the basal levels of corticosterone but did not alter the basal levels of ACTH or oxytocin. Also, this diet inhibited the magnitude of 8-OH-DPAT-induced increase in plasma levels of ACTH and oxytocin but did not impair the ability of fluoxetine to desensitize the 5-HT1A receptor-mediated increase in plasma hormones. These data suggest that a reserve of 5-HT enables fluoxetine to desensitize postsynaptic 5-HT1A receptors in the hypothalamus. In conclusion, the profound physiological changes induced by tryptophan depletion may complicate the interpretation of studies using this experimental approach.
D'Souza
D N
DN
Dept. of Pharmacology, Loyola Univ. of Chicago, School of Medicine, 2160 South First Ave., Maywood, IL 60153, USA.
Zhang
Y
Y
Garcia
F
F
Battaglia
G
G
Van de Kar
L D
LD
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004032:Diet; D005473:Fluoxetine / Q000494:pharmacology*; D006728:Hormones / Q000378:metabolism*; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism*; D010121:Oxytocin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014364:Tryptophan / Q000172:deficiency*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D005473:Fluoxetine; D006728:Hormones; D010121:Oxytocin; D044263:Receptors, Serotonin, 5-HT1; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan