Serotonergic effects on feeding, but not hypothalamus-pituitary-adrenal secretion, are altered in ovine pregnancy

Abstract

Lingis M, Richards E, Perrone D, Keller-Wood M. Serotonergic effects on feeding, but not hypothalamus-pituitary-adrenal secretion, are altered in ovine pregnancy. Am J Physiol Endocrinol Metab 302: E1231-E1238, 2012. First published February 28, 2012 doi:10.1152/ajpendo.00582.2011In ovine pregnancy, as in human pregnancy, hypothalamus-pituitary-adrenal activity is chronically increased. These studies were designed to test the hypotheses that expression of serotonergic genes and responsiveness to serotonin are increased in pregnancy. We tested the stimulatory effect of an acute, intracerebroventricular injection of the serotonin reuptake inhibitor fluoxetine on plasma ACTH and cortisol in ewes during late pregnancy or postpartum. We also tested the effect of lower-dose, longer-term stimulation by intracerebroventricular infusion of fluoxetine in pregnant and nonpregnant ewes over 6 days. Overall, we found that the stimulatory effect of fluoxetine on ACTH and cortisol was not significantly different between late-gestation and nonpregnant ewes, although the effect of acute fluoxetine administration was inversely related to plasma progesterone concentrations. Also, there were no differences in hypothalamic expression of the glucocorticoid and mineralocorticoid receptors, corticotropin-releasing hormone, AVP, the serotonin reuptake transporter, or the serotonin [5-hydroxytryptamine (5-HT)] receptors 5-HT 1A and 5-HT2A with pregnancy or fluoxetine treatment. However, chronic fluoxetine infusion reduced food intake in the nonpregnant, but not pregnant, ewes. Expression of proopiomelanocortin mRNA in the hypothalamus was reduced in pregnant compared with nonpregnant ewes. Our results indicate that pregnancy does not increase responsiveness of ACTH and cortisol to serotonergic stimulation but, rather, that progesterone reduces the ACTH response. In addition, we found a reduced ability of serotonin to inhibit feeding in the pregnant ewes, consistent with a reduction in anorexic mechanisms in the pregnant state. adrenocorticotropic hormone; cortisol; proopiomelanocortin; serotonin THE SEROTONERGIC SYSTEM is one of the stimulatory inputs to the hypothalamus-pituitary-adrenal (HPA) axis (9, 15). In the rat, serotonergic axons synapse on neurons in the paraventricular nucleus of the hypothalamus (PVN), which contain corticotropin-releasing hormone (CRH), and serotonin directly stimulates CRH release in hypothalamic cultures (10). In vivo administration of serotonin [5-hydroxytryptamine (5-HT)], its precursors, or 5-HT receptor agonists in humans and animal models, including sheep, increases plasma ACTH and cortisol (7,9,15,(21)(22)(23)26; reviewed in Ref. 12). Selective serotonin reuptake inhibitors (SSRIs), which act on the transporter responsible for removing serotonin from the synaptic cleft, also acutely increase plasma ACTH concentrations (16,22). Serotonin-induced stimulation of ACTH involves hypothalamic 5-HT 1A and 5-HT 2A receptors (reviewed in Ref. 12).Studies in several species suggest that gonadal steroids may al...

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“…This is illustrated by the results of the study, wherein the long-term stimulation of nonpregnant ewes by intracerebroventricular infusion of fluoxetine reduced food intake but had no influence on the expression of proopiomelanocortin mRNA in the hypothalamus. However, such infusion into pregnant ewes decreased the production of proopiomelanocortin but did not change significantly the feeding behavior [ 101 ]. It should be taken into account that the acute or short-term treatment of animals with centrally administered SSRI, serotonin and 5-HTR agonists, led to the results which differed considerably from those obtained in the case of chronic treatment.…”

The use of anxiolytic drugs for the correction of behavioral disorders in mammals

“…Fluoxetine does not adversely affect the appetite of pregnant ewes (Lingis, 2012). However, according to Nguyen et al (2011), motor hyperactivity of lambs under antenatal fluoxetine exposure may indicate an increased rate of brain maturation.…”