The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats

2005 ◽  
Vol 288 (6) ◽  
pp. R1486-R1491 ◽  
Author(s):  
Lisa A. Eckel ◽  
Heidi M. Rivera ◽  
Deann P. D. Atchley

The controls of food intake differ in male and female rats. Daily food intake is typically greater in male rats, relative to female rats, and a decrease in food intake, coincident with the estrous stage of the ovarian reproductive cycle, is well documented in female rats. This estrous-related decrease in food intake has been attributed to a transient increase in the female rat's sensitivity to satiety signals generated during feeding bouts. Here, we investigated whether sex or stage of the estrous cycle modulate the satiety signal generated by fenfluramine, a potent serotonin (5-HT) releasing agent. To examine this hypothesis, food intake was monitored in male, diestrous female, and estrous female rats after intraperitoneal injections of 0, 0.25, and 1.0 mg/kg d-fenfluramine. The lower dose of fenfluramine decreased food intake only in diestrous and estrous females, suggesting that the minimally effective anorectic dose of fenfluramine is lower in female rats, relative to male rats. Although the larger dose of fenfluramine decreased food intake in both sexes, the duration of anorexia was greater in diestrous and estrous female rats, relative to male rats. Moreover, the magnitude of the anorectic effect of the larger dose of fenfluramine was greatest in estrous rats, intermediate in diestrous rats, and least in male rats. Thus our findings indicate that the anorectic effect of fenfluramine is modulated by gonadal hormone status.

2001 ◽  
Vol 91 (5) ◽  
pp. 2005-2009 ◽  
Author(s):  
Christian K. Roberts ◽  
Nosratola D. Vaziri ◽  
R. James Barnard

Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hormone status in the development and reversibility of hypertension. Normal male and female and ovariectomized (OVX) female Fischer rats were placed on either a high-fat (primarily saturated), refined carbohydrate (sucrose) (HFS) or a low-fat, complex carbohydrate (LFCC) diet at 2 mo of age, and body weight and systolic blood pressure (BP) were measured. Male and OVX female rats were initially on the diets for 7 mo, whereas normal female rats were on the diets for 2 yr. After this initial phase, a group of rats from each of the normal HFS groups were converted to the LFCC diet for a period of 1 mo (males) and 2 mo (females). The OVX females were subcutaneously implanted with a 0.5-mg estradiol (E2) pellet for 1 mo. A significant rise in arterial BP occurred within 12 mo in female and only 2 mo in male rats on the HFS diet, exceeding 140 mmHg after 24 and 7 mo, respectively. Conversion from the HFS to the LFCC diet led to a normalization of BP in both female and male rats. HFS diet-induced hypertension was accelerated by OVX in female rats, approaching the pattern seen in male rats. The effect of OVX was completely reversed by E2replacement. BP did not significantly change in any of the LFCC groups at any time point, and E2 replacement had no effect on BP in the OVX LFCC group. All HFS groups had significantly greater body weight, with differences occurring sooner in the male and OVX rats compared with the female rats. Diet modification resulted in a partial but significant reduction of body weight, but E2replacement did not. These results demonstrate that long-term consumption of HFS diet induces hypertension in both genders and is reversible by diet modification. Hypertension is significantly delayed in females with functional ovaries. This protection is lost by OVX and restored by estrogen replacement. Thus hormone status contributes to the delayed onset of diet-induced hypertension in females compared with males.


2013 ◽  
pp. S99-S108 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
E. MACÚCHOVÁ ◽  
K. NOHEJLOVÁ-DEYKUN ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
...  

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.


1989 ◽  
Vol 257 (6) ◽  
pp. R1417-R1422 ◽  
Author(s):  
S. Rivest ◽  
Y. Deshaies ◽  
D. Richard

The purpose of this study was to investigate the effects of a chronic intracerebroventricular administration of corticotropin-releasing factor (CRF) on energy balance of male and female rats. One week after their delivery to the laboratory, both male and female rats were divided into two groups. One group in each sex was treated with human/rat CRF, while another group was infused with the vehicle. Chronic administration of CRF was accomplished by means of miniosmotic pumps connected to a cannula that was stereotaxically directed into the third ventricle. Food intake and body weight were measured each day during the study. After 14 days of treatment, the rats were killed by decapitation. Energy, fat, and protein contents of the carcasses were quantified. Serum testosterone and estradiol were assayed in males and females, respectively. Administration of CRF significantly reduced body weight gain and food intake in male rats. No significant difference in those variables was observed between female rats treated with CRF and their controls infused with saline. Similarly, metabolizable energy intake and body energy gain were reduced in male rats infused with CRF, whereas no difference was observed between female animals treated with CRF and those infused with saline. In male rats, body fat and body protein contents were lower in CRF-treated than in saline-infused rats. In female rats, CRF did not affect body composition. Serum testosterone in male rats and serum estradiol in female animals were reduced after chronic infusion of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)


1989 ◽  
Vol 257 (4) ◽  
pp. R738-R743 ◽  
Author(s):  
J. T. Crofton ◽  
L. Share

To examine the osmotic control of vasopressin release, hypertonic saline was infused in conscious unrestrained male rats and female rats in each phase of the estrous cycle. The progressive increase in plasma osmolality was accompanied by a progressive increase in the plasma vasopressin concentration, but the magnitude of the former was smaller in metestrus than in other phases of the cycle and in males (P less than 0.01). The osmotic threshold for vasopressin release was higher in males than in females in each phase of the estrous cycle (P less than 0.05 to P less than 0.01), but the sensitivity of the osmotic control of vasopressin release was similar in male and female rats. Although the pressor response to hypertonic saline was greater in estrous females than in the other females (P less than 0.05 to P less than 0.01), the reduction in blood pressure, after a V1 antagonist 30 min after starting the hypertonic saline infusion, was similar in males and females. Thus there are gender-related differences in the osmotic control of vasopressin release and, in females, cycle-dependent differences in the cardiovascular responses to hypertonic saline.


1987 ◽  
Vol 113 (3) ◽  
pp. 479-484 ◽  
Author(s):  
M. N. Sillence ◽  
R. G. Rodway

ABSTRACT The effects of the adrenal inhibitor trilostane were examined in male and female rats to determine whether growth rate could be improved by lowering circulating plasma corticosterone concentrations. Dose–response studies revealed that in young female rats (125 g) trilostane lowered peak plasma corticosterone levels in a dose-dependent manner. In male rats plasma corticosterone concentrations were reduced only by very high doses of trilostane (200 mg/kg), while lower doses (2–8 mg/kg) actually increased them. Five growth studies were conducted using a total of 90 rats. In female animals, daily injections of trilostane (10 mg/day) caused an age-dependent increase in growth rate ranging from 11% in 127 g rats to 30% in 164 g rats. In three out of four experiments using females, food intake was slightly increased by the drug. Food conversion efficiency was improved consistently by trilostane by up to 18%. Trilostane-treated females had significantly heavier adrenal glands and livers, but lighter kidneys than control rats. When a complete carcass analysis was performed on one experimental group, no significant differences were found. Carcass component weights relative to control values were: body weight (103%), body water (105%), fat-free solids (103%), carcass weight (103%), body length (103%), body fat (95%) and gut content (96%). In male rats (160 g), daily injections of trilostane (10 mg) resulted in a steady and sustained depression of growth rate reflecting a similar fall in food intake, with no change in food conversion efficiency. It is concluded that in older female rats growth rate is constrained by physiological concentrations of glucocorticoids. Younger females are either less sensitive to trilostane or to changes in plasma corticosterone levels. Male rats are less responsive to adrenal suppression by trilostane than are females of a similar age and do not exhibit an anabolic response to this drug. J. Endocr. (1987) 113, 479–484


1953 ◽  
Vol 31 (5) ◽  
pp. 377-386
Author(s):  
Jules Tuba ◽  
G. Stuart Wiberg

A dextrinogenic micromethod was used to establish serum amylase levels in adult male and female rats which were maintained on a standard laboratory diet. A highly significant difference was found to exist between the activities of the enzyme in the male and female rats. The effect of fasting, and of limiting food consumption, indicated a highly significant correlation between daily food intake and serum amylase levels. The polyphagia manifested by alloxan diabetic rats was not reflected in abnormally high amylase activity, as might be expected, but there was a departure from the normal response to the levels of food ingested each day. Oestradiol dipropionate and testosterone propionate were injected into normal male and female rats for seven days. Treatment with male hormone produced no significant variation in food consumption or serum amylase activity in either sex. Injections with oestradiol resulted in significantly lowered food intake in both sexes, but only in the case of males was there an accompanying fall in enzyme levels. On the basis of the experiments described in this paper it is seen that rat serum amylase consists of two fractions, and that the major portion may be considered to be of an adaptive nature. This adaptive portion appears to a large measure to be a reflection of the total daily food intake, which may be influenced by certain factors, such as sex hormones and alloxan diabetes.


Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2689-2699 ◽  
Author(s):  
A. C. Kentner ◽  
S. A. McLeod ◽  
E. F. Field ◽  
Q. J. Pittman

Inflammatory molecules, such as cyclooxygenase (COX), a prostaglandin synthetic enzyme, have been identified as a marker of depressive symptomology. Previously, we have observed elevated basal COX-2 expression in the hypothalamus of adult male rats treated neonatally with lipopolysaccharide (LPS), which might suggest a phenotype for disrupted hedonic behavior, a symptom of depression. However, COX-2 and its contribution to the expression of anhedonic behavior has not been investigated in these males or in female rats across the estrous cycle, which is the purpose of the current work. Here, we examine the effects of a neonatal LPS challenge or saline on the sucrose preference test as a measure of anhedonia, and hypothalamic COX-2 expression, in adult male and freely cycling female rats. Our data indicate a sex difference in that neonatal LPS at postnatal d 14 causes elevated basal expression of hypothalamic COX-2 in male, but not in female, rats. Additionally, baseline sucrose preference in male and female rats was unaltered as a function of neonatal LPS treatment or estrous cycle stage. In both male and female animals, 50 μg/kg LPS in adulthood caused elevated plasma IL-6 and hypothalamic COX-2 expression in neonatally saline-treated rats but significantly less so in neonatally LPS-treated rats of both sexes; this neonatal programming was not evident for sucrose preference or for total fluid intake (even after much higher doses of LPS). Our data are suggestive of a dissociation between inflammation and anhedonic behavior and a differential effect of neonatal inflammation in males and females.


2008 ◽  
Vol 295 (6) ◽  
pp. R1747-R1753 ◽  
Author(s):  
Sean Z. Goodin ◽  
Alicia R. Keichler ◽  
Marissa Smith ◽  
Donna Wendt ◽  
April D. Strader

Agouti-related peptide (AgRP), the endogenous antagonist to the melanocortin 3 and 4 receptors, elicits robust hyperphagia and weight gain in rodents when administered directly into the central nervous system. The relative influence of AgRP to cause weight gain in rodents partially depends on the activity level of the melanocortin agonist-producing proopiomelanocortin neurons. Both proopiomelanocortin and AgRP neurons within the arcuate nucleus receive energy storage information from circulating peripheral signals such as leptin and insulin. Another modulator of AgRP activity includes the cell surface molecule syndecan-3. Because leptin and insulin affect food intake in a sexually dimorphic way in rodents and syndecan-3-deficient mice regulate adiposity levels through distinct physiological mechanisms, we hypothesized that AgRP-induced weight gain would also be sexually dimorphic in rats. In the present study, the behavioral and physiological effects of centrally-administered AgRP in male and female were investigated. In male rats, AgRP (1 nmol) induced 5 days ( P < 0.0001) of significantly elevated feeding compared with vehicle-treated controls, while females displayed 3 days of hyperphagia ( P < 0.05). However, 1 wk after the injection, both male and female rats gained the same percent body weight (6%). Interestingly, female rats exhibited a greater reduction in energy expenditure (vo2) following AgRP compared with male rats ( P < 0.05). Removal of the gonads did not alter cumulative food intake in male or female rats but did attenuate the dramatic reduction in Vo2 exhibited by females. Both intact and gonadectomized rats demonstrated significantly increased respiratory quotient supporting the anabolic action of AgRP ( P < 0.01). These findings are novel in that they reveal sex-specific underlying physiology used to achieve weight gain following central AgRP in rats.


Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 523-533 ◽  
Author(s):  
Christophe Lenglos ◽  
Juliane Calvez ◽  
Elena Timofeeva

This study compared the effects of relaxin-3 (RLN3) on food intake, plasma corticosterone, and the expression of corticotropin-releasing factor (CRF) in male and female rats. RLN3 was injected into the lateral ventricle at 25, 200, and 800 pmol concentrations. RLN3 at 25 pmol increased food intake (grams) at 30 and 60 minutes after injection in female but not male rats. Female rats also showed higher increase in relative to body weight (BW) food intake (mg/g BW) for all RLN3 concentrations at 30 minutes and for 800 pmol of RLN3 at 60 minutes. Moreover, RLN3 at 800 pmol significantly increased 24-hour BW gain in female but not male rats. At 60 minutes after administration, 800 pmol of RLN3 produced a significant increase in plasma corticosterone and in the expression of CRF and c-fos mRNAs in the parvocellular paraventricular hypothalamic nucleus (PVN) in male but not female rats. The levels of c-fos mRNA in the magnocellular PVN were increased by RLN3 but did not differ between the sexes. Conversely, expression of CRF mRNA in the medial preoptic area was increased in female rats but was not sensitive to 800 pmol of RLN3. In the bed nucleus of the stria terminalis, 800 pmol of RLN3 significantly increased CRF mRNA expression in female but not male rats. Therefore, female rats showed more sensitivity and stronger food intake increase in response to RLN3. The differential effects of RLN3 on CRF expression in the PVN and bed nucleus of the stria terminalis may contribute to the sex-specific difference in the behavioral response.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Paula S. Dornellas ◽  
Giovana C. Macedo ◽  
Minna H. McFarland ◽  
Alexander Gómez-A ◽  
Todd K. O’Buckley ◽  
...  

Mesolimbic dopamine transmission is dysregulated in multiple psychiatric disorders, including addiction. Previous studies found that the endogenous GABAergic steroid (3α,5α)-3-hydroxy-5-pregnan-20-one (allopregnanolone) modulates dopamine levels in the nucleus accumbens and prefrontal cortex. As allopregnanolone is a potent positive allosteric modulator of GABAA receptors, and GABAA receptors can regulate dopamine release, we hypothesized that allopregnanolone would reduce phasic fluctuations in mesolimbic dopamine release that are important in learning and reward processing. We used fast-scan cyclic voltammetry in anesthetized female and male rats to measure dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area, before and after administration of allopregnanolone. Allopregnanolone (7.5–25 mg/kg, IP) reduced evoked dopamine release in both male and female rats, compared to β-cyclodextrin vehicle. In males, all doses of allopregnanolone decreased dopamine transmission, with stronger effects at 15 and 25 mg/kg allopregnanolone. In females, 15 and 25 mg/kg allopregnanolone reduced dopamine release, while 7.5 mg/kg allopregnanolone was no different from vehicle. Since allopregnanolone is derived from progesterone, we hypothesized that high endogenous progesterone levels would result in lower sensitivity to allopregnanolone. Consistent with this, females in proestrus (high progesterone levels) were less responsive to allopregnanolone than females in other estrous cycle stages. Furthermore, 30 mg/kg progesterone reduced evoked dopamine release in males, similar to allopregnanolone. Our findings confirm that allopregnanolone reduces evoked dopamine release in both male and female rats. Moreover, sex and the estrous cycle modulated this effect of allopregnanolone. These results extend our knowledge about the pharmacological effects of neurosteroids on dopamine transmission, which may contribute to their therapeutic effects.


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