Sex differences in the reversal of fluoxetine-induced anorexia following raphe injections of 8-OH-DPAT.
OBJECTIVE
Serotonin (5-hydroxytryptamine, 5-HT) is widely distributed in the central nervous system and it is well established that this neurotransmitter plays an inhibitory role in the control of ingestive behavior. Administration of various 5-HT agonists and selective serotonin reuptake inhibitors, including fluoxetine (FLU), suppress food intake under free-feeding and food-restricted conditions. In contrast, activation of somatodendritc 5-HT(1A) receptors in the raphe nuclei reduces forebrain 5-HT bioavailability and agonists of these receptors, including 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), reliably stimulate eating behavior.


METHODS
In the present study male ( n=8 per group) and female ( n=8 per group) rats were pretreated with 8-OH-DPAT in an attempt to reverse FLU's inhibitory effect on feeding. 8-OH-DPAT was injected into either the dorsal or median raphe of male and female rats at doses of 0.1-0.4 nmol. FLU was then injected IP at a dose of 2 mg/kg. Both compounds were administered just prior to the onset of the dark cycle. Food intake was measured 2 h post-injection. Similar effects were also measured in female rats after ovariectomy.


CONCLUSIONS
FLU suppressed food intake comparably in male and female rats. Dorsal and median raphe injections of 8-OH-DPAT dose dependently reversed the anorectic effect of FLU in male rats. Higher doses of 8-OH-DPAT completely antagonized this response. In female rats, however, 8-OH-DPAT pretreatment was largely ineffective except in ovariectomized females where results were similar to male rats. These findings suggest that male and female rats are differentially sensitive to the ability of 5-HT(1A) receptor agonists to antagonize the feeding suppressive action of FLU and imply a role for neuroendocrine mechanisms in enabling the somatodendritic autoreceptor to control serotonergic neurotransmission under these conditions.
Currie
Paul J
PJ
Department of Psychology, Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, USA. pjc37@columbia.edu
Braver
Melissa
M
Mirza
Aaisha
A
Sricharoon
Krisna
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects*; D008297:Male; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D012737:Sex Factors
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors