- Email: [email protected]
Gender mainstreaming in health care: Will it stop bias?
POSTER PRESENTATIONS
cohort. B a c k g r o u n d : MetSyn constitutes a major public h e a l t h p r o b l e m with differences in prevalence by gender. D e s i g n / M e t h o d s : As part of the Northern M a n h a t t a n Study, 3297 c o m m u n i t y residents (2077 women) were prospectively followed for a m e a n of 6.5 years. MetSyn was defined b y ATP III. Cox models estimated hazard ratios (HR) a n d 95% CI for vascular events (stroke, MI, or vascular death). Population-level attributable risk for MetSyn was calculated. Logistic regression explored the association between SES a n d MetSyn. R e s u l t s : Over 46% of w o m e n (mean 68 years) h a d MetSyn. MetSyn was significantly greater in w o m e n (W) t h a n m e n (M): vascular risk ([W] 1.8; 95% CI, 1.36, 2.38 vs. [M] 1.4; 95% CI, 1.0-1.9) after a d j u s t m e n t for age, ethnicity, education, a n d risk factors a n d accounted for 27% of vascular events in W. We identified two subgroups: M e t S y n l - a c o m b i n a t i o n of blood pressure, blood glucose, a n d HDL; a n d M e t S y n 2 - a n y o t h e r ATP III c o m b i n a t i o n . After adjustment, the effect of MetSynl o n vascular risk was similar for W (HR 2.9; 95% CI [1.7M.8]) a n d M (HR 2.0; 95% CI [1.1-3.6]). MetSyn2 was only associated with vascular risk in W (HR 1.5; 95% CI [1.0-2.3]). W o m e n w i t h MetSyn were significantly more likely be Hispanic (1.6, 95% CI 1.2-2.1), socially isolated (1.4, 95% CI 1.05-1.8), a n d inactive (1.3, 95% CI 1.0-1.4). C o n c l u s i o n s : Metabolic syndrome m a y be a more i m p o r t a n t risk factor for vascular events in women. Lack of social resources m a y contribute to the d e v e l o p m e n t of metabolic syndrome.
13
Sex-Different Regulation of Fatty Acid Translocase/CD36 Expression in Rat Liver Louisa C h e u n g l ; M a l i n Andersen2; N i n a Stahlbergl; A m i l c a r Flores-Moralesl; L e a n d r o Fernandez3; J a c o b Odenberg2; G u n n a r Norstedtl; a n d Petra Tollet-Egnell 1
iDepartment of Molecular Medicine and Surge~ Kamlinska Institute, Stockholm, Sweden; 2Department of Biotechnology, Royal Institute of Technology, Stockholm, Sweden; and 3Pharmacology Section, Department of Clinical Sciences, Health Sciences CenteB Universityof Lus Palmus de Gran CanariG Canary Islands, Spain Based o n data from microarray analyses, fatty acid translocase (FAT or CD36) is a m o n g the most sex-differentiated gene products in rat liver, with lO-fold higher mRNA levels in females. CD36 is a nmltiligand cell surface receptor associated with a broad array of physiological processes and involved in markedly diverse disorders, including atherosclerosis, dyslipidemia, insulin resistance, a n d diabetes. Sexdifferent regulation of CD36 expression m i g h t therefore contribute to sex-different onset or severity of metabolic disease. The purpose of this study was to determine the molecular mechanisms b e h i n d the female-predominant expression of this gene. Hepatic CD36 mRNA levels were determined by RT-PCR in rats of different h o r m o n a l and nutritional status, identifying b o t h estradiol and growth h o r m o n e as regulators. Different first exon usage was observed, w h i c h motivated sequencing of the " u n k n o w n " exon lb. Based o n in silico promoter analysis by CONSITE, a region 200-bp upstream of exon l b showed high sequence similarity between h u m a n , mouse, a n d rat sequences. Many putative transcription factor b i n d i n g sites were located within this region. None of these have previously been associat-
ed with sex-different gene expression. Some were confirmed by gel-shift assay, showing sex-preferential b i n d i n g activity.
14
Cross-Species Comparison of Hepatic Sex Differences Identified in Transcript Profiles Louisa Cheung; Elizabeth Rico-Bautista; G u n n a r Norsted; a n d Petra Tollet-Egnell
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden Sex-related differences in b o d y composition a n d onset of metabolic disease m i g h t be related to differences in the metabolism of carbohydrates a n d lipids. More knowledge c o n c e r n i n g sex differences in fuel metabolism a n d the m e c h a n i s m s b e h i n d this m i g h t therefore help us to understand w h y w o m e n to some extent are protected against metabolic disorders a n d cardiovascular disease. We have recently described the utility of gene arrays to identify sexrelated gene products in rat liver. Here we have extended this initial study to include sex-dependent transcript profiles from rat, mouse, a n d h u m a n liver. The online software DAVID was used to classify the obtained profiles into functional groups. Regardless of species, 15% of the genes represented o n the arrays were expressed a n d roughly 15% of those were sex-differentiated. Some interesting functional groups were identified, such as lipid metabolism, insulin signaling, a n d i m m u n e responses. W i t h i n these functional groups of transcripts, specific genes with a sex-differentiated expression in all three species were identified. It seems likely t h a t sets of genes from specific metabolic pathways m a y be regulated in a coordinated manner. Identification of prom o t e r sequences a n d cis-regulatory elements shared by this set of co-regulated genes m i g h t lead to the characterization of c o m m o n l y used transcription factors a n d upstream signaling pathways.
15
Gender Mainstreaming in Health Care: Will It Stop Bias? Alice C h w o s t a l ; Angelika Bader2; Doris Musshauserl; a n d M a r g a r e t h e H o c h l e i t n e r 3
iLudwig Boltzmann Institute for Gender Studies, Tyrol±Austria; eWomen's Health Office of the State of Tyrol, Austria; and 3Innsbruck Medical University, Tyrol' Austria Heart d e a t h is the n u m b e r - o n e killer for w o m e n a n d bias in cardiology is well documented. Can we prove a n y change due to the EU action plan o n gender mainstreaming? In 2000, we conducted a prospective study o n high-tech cardiology for Tyrol/Austria including mortality and p o p u l a t i o n statistics a n d compared these data with 1995, a year prior to gender m a i n s t r e a m i n g health-care. In Tyrol, more w o m e n t h a n m e n have died due to a cardiac d e a t h t h r o u g h o u t decades. In 1995, 1008 females a n d 875 males, a n d in 2000, 1104 females a n d 792 males were registered. In 2000, 128 (43.5%) w o m e n a n d 166 (56.5%) m e n got a pacemaker; in 1995, 96 (46.6%) w o m e n and 110 (53.4%) men. A total of 688 (32.5%) w o m e n a n d 1429 (67.5%) m e n u n d e r w e n t coronary aniography. In 1995, 332 (33.9%) women, a n d 646 (66.1%) m e n received CA. In 2000, 42 (27.5%) w o m e n a n d 157 (72.5%) m e n underwent bybass surgery; in 1995, there were 54 (33.0%) w o m e n a n d 156 (67.0%) men. The $47
GENDERMEDICINE
demographic data show hardly any change; however, the mortality statistics show an increase of 9.5% for female heart deaths, but a decrease of 9.5% in males. In conclusion, all interventions show a decrease in females percentage and worst of all, we see a remarkable increase in female heart deaths. Although the coronary angiography capacity was doubled between 1995 and 2000 and the n u m b e r of coronary angiographies increased also in women, the bias against w o m e n was even worse. So these data demonstrate no benefit for w o m e n at all. Of course, sociopsychological changes need m u c h longer t h a n five years. So let's hope for the best!
16 Gender Differences in the Relation Between Ambulatory Blood Pressure and Left Ventricular Mass in Hypertensive Outpatients Franco Cipollini2; Flavia Franconil; Carlo Porta2; Enrica Arcangeli2; a n d Giuseppe Seghieri 2
iDept. Scienze del Farmaco-universita di Sassari, Italy; and 2Centroper l'ipertensione, Spedali Riuniti, Pistoia, Italy B a c k g r o u n d a n d Aims: Since gender seems to have a role in modulating the relation between hypertension and left ventricular hypertrophy (LVH), the aim of this study was to investigate whether left ventricular mass (LVM) is differently related to blood pressure (BP) in male compared to female patients. P a t i e n t s a n d M e t h o d s : We monitored 24-h ambulatory BP and measured LVM (by echographic method) in 151 (81M/70F) patients, consecutively referred to our unit to confirm hypertension or to modify therapy. Results: Twenty-four-hour systolic BP was similar in men, and in preor postmenopausal women, while 24-h diastolic BP was lower and pulse BP higher in postmenopausal women. LVH prevalence was highest in postmenopausal women, and LVM weighted more in n o n dippers t h a n in dippers in m e n (P = 0.008), in postmenopausal (P = 0.0004), but n o t premenopausal women. Percentage of LVM variance explained by systolic and diastolic BP was h i g h e r a m o n g premenopausal women, while 24-h pulse BP was about 5- to 6-fold more predictive of LVM variance in women. For every 1-mm Hg increase in either mean 24-h systolic- or pulse-BP the adjusted relative risk for LVH was 2- to 3-fold higher in w o m e n t h a n in men. Nondippers had a higher adjusted relative risk for LVH only in w o m e n (OR 7.88; 95% CI 1.37-45.4 in women; OR 2.47; 95% CI 0.67-9.13 in men). C o n c l u s i o n s : Gender is an important modulator of LVM dependence by BP. Pulse BP is a strong i n d e p e n d e n t predictor of LVM, especially and specifically in women, either prior to or after menopause, while n o n dippers are associated with LVH a m o n g women, stressing once again their different response to a same long-acting blood BP load. 17
Gender Specific Differences in Left Ventricular Hypertrophy in DOCA-Salt Mice With Hypertensive Kidney Disease Aysun Karatasl; Melina Nieminen-Kelha2; M a x i m Krikov3; Yvonne Linde2; Bjorn Hegner2; a n d Duska Dragun 2
iDepartment of Nephrology and Center for Cardiovascular Research (CCR), University Hospital Charite Campus Mitre, Berlin, Germany; 2Department of Nephrology, UniversityHospital Charite Campus Mitre, Berlin, Germany; and 3Institute of $48
Toxikology and Pharmakology, Center for Cardiovascular Research (CCR), Charite Campus Mitre, Berlin, Germany In chronic renal failure, volume overload and hypertension due to aldosterone excess lead to combination of concentric and eccentric hypertrophy. Deoxycorticosterone acetate (DOCA) mimics aldosterone by stimulation of sodium reabsorbtion in the kidney collecting ducts. Consequently, mice develop renal disease and left ventricular hypertrophy within 3-6 weeks. Signaling by the calcium-dependent phosphatase calcineurin contributes to cardiac hypertrophy in response to pathologic stimuli. Whether or not activation of calcineurin-signaling displays gender-specific differences has not been investigated yet. We hypothesized that putative gender differences in the activation of calcineurin-signaling in DOCA-salt model are estrogen dependent and mediated through estrogen-receptors. In order to differentiate blood pressure-dependent from independent effects, we will employ pharmacological intervention with hydralazine. DOCA pellets were implanted to uninephrectomized female and male C57BL/6J mice receiving a high salt diet. Blood pressure and urinary excretion were monitored weekly. At the endpoints, after 3 or 6 weeks the invasive blood pressure measurement was performed and hearts and kidneys were harvested. We studied structural and molecular markers of cardiac and renal hypertrophy and fibrosis. We preliminarily show that DOCA-salt induces volume overload and hypertension in a gender independent manner. Yet, female mice display a trend of increased renal and decreased cardiac hypertrophy implicating better adaptation to injurious stimulus. Hearts and kidneys show signs of beginning fibrosis and glomerulosclerosis in a gender dependent manner. Further experiments are directed to investigate gender specificity in the calcineurin pathway and the role of estrogen receptors.
18
Dopamine D1 Receptor Involvement in the Antidepressant-like Effect of AIIopregnanolone in the Forced Swimming Test Paolo S. D'Aquila; Marco Sardella; Maria E. Canu; Davide Carta; G i u s e p p i n a M o n n i ; Serra Gino; a n d Flavia F r a n c o n i
Dipartimento di Scienze del Farmaco, Universita di Sassari, Italy Women are more susceptible than m e n to major depression and may develop mood disturbances related to their reproductive cycle. Among the factors that may account for such gender difference, neurosteroids seem to play a major role. Evidence has been produced showing the involvement of neurosteroids, and in particular of allopregnanolone, both in the mechanism of action of antidepressants and in depressive-like behavior in animal models. Previous studies performed in male subjects have shown that dopamine D1 receptor stimulation results in an antidepressant-like effect and is critical for the expression of the effect of antidepressant drugs in the forced swimming model of depression. In the present study we examined, in Sprague-Dawley female rats, the effect of the dopamine D1 receptor antagonist SCH 23390 (0.01 and 0.025 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the forced swimming test. Since in preliminary experiments we failed to show in this strain of rats any difference in this test related to the phase of oeslxous cycle both in basal conditions and after allopregnanolone adminislxation, the subjects were tested regardless of their oes~us cycle
cohort. B a c k g r o u n d : MetSyn constitutes a major public h e a l t h p r o b l e m with differences in prevalence by gender. D e s i g n / M e t h o d s : As part of the Northern M a n h a t t a n Study, 3297 c o m m u n i t y residents (2077 women) were prospectively followed for a m e a n of 6.5 years. MetSyn was defined b y ATP III. Cox models estimated hazard ratios (HR) a n d 95% CI for vascular events (stroke, MI, or vascular death). Population-level attributable risk for MetSyn was calculated. Logistic regression explored the association between SES a n d MetSyn. R e s u l t s : Over 46% of w o m e n (mean 68 years) h a d MetSyn. MetSyn was significantly greater in w o m e n (W) t h a n m e n (M): vascular risk ([W] 1.8; 95% CI, 1.36, 2.38 vs. [M] 1.4; 95% CI, 1.0-1.9) after a d j u s t m e n t for age, ethnicity, education, a n d risk factors a n d accounted for 27% of vascular events in W. We identified two subgroups: M e t S y n l - a c o m b i n a t i o n of blood pressure, blood glucose, a n d HDL; a n d M e t S y n 2 - a n y o t h e r ATP III c o m b i n a t i o n . After adjustment, the effect of MetSynl o n vascular risk was similar for W (HR 2.9; 95% CI [1.7M.8]) a n d M (HR 2.0; 95% CI [1.1-3.6]). MetSyn2 was only associated with vascular risk in W (HR 1.5; 95% CI [1.0-2.3]). W o m e n w i t h MetSyn were significantly more likely be Hispanic (1.6, 95% CI 1.2-2.1), socially isolated (1.4, 95% CI 1.05-1.8), a n d inactive (1.3, 95% CI 1.0-1.4). C o n c l u s i o n s : Metabolic syndrome m a y be a more i m p o r t a n t risk factor for vascular events in women. Lack of social resources m a y contribute to the d e v e l o p m e n t of metabolic syndrome.
13
Sex-Different Regulation of Fatty Acid Translocase/CD36 Expression in Rat Liver Louisa C h e u n g l ; M a l i n Andersen2; N i n a Stahlbergl; A m i l c a r Flores-Moralesl; L e a n d r o Fernandez3; J a c o b Odenberg2; G u n n a r Norstedtl; a n d Petra Tollet-Egnell 1
iDepartment of Molecular Medicine and Surge~ Kamlinska Institute, Stockholm, Sweden; 2Department of Biotechnology, Royal Institute of Technology, Stockholm, Sweden; and 3Pharmacology Section, Department of Clinical Sciences, Health Sciences CenteB Universityof Lus Palmus de Gran CanariG Canary Islands, Spain Based o n data from microarray analyses, fatty acid translocase (FAT or CD36) is a m o n g the most sex-differentiated gene products in rat liver, with lO-fold higher mRNA levels in females. CD36 is a nmltiligand cell surface receptor associated with a broad array of physiological processes and involved in markedly diverse disorders, including atherosclerosis, dyslipidemia, insulin resistance, a n d diabetes. Sexdifferent regulation of CD36 expression m i g h t therefore contribute to sex-different onset or severity of metabolic disease. The purpose of this study was to determine the molecular mechanisms b e h i n d the female-predominant expression of this gene. Hepatic CD36 mRNA levels were determined by RT-PCR in rats of different h o r m o n a l and nutritional status, identifying b o t h estradiol and growth h o r m o n e as regulators. Different first exon usage was observed, w h i c h motivated sequencing of the " u n k n o w n " exon lb. Based o n in silico promoter analysis by CONSITE, a region 200-bp upstream of exon l b showed high sequence similarity between h u m a n , mouse, a n d rat sequences. Many putative transcription factor b i n d i n g sites were located within this region. None of these have previously been associat-
ed with sex-different gene expression. Some were confirmed by gel-shift assay, showing sex-preferential b i n d i n g activity.
14
Cross-Species Comparison of Hepatic Sex Differences Identified in Transcript Profiles Louisa Cheung; Elizabeth Rico-Bautista; G u n n a r Norsted; a n d Petra Tollet-Egnell
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden Sex-related differences in b o d y composition a n d onset of metabolic disease m i g h t be related to differences in the metabolism of carbohydrates a n d lipids. More knowledge c o n c e r n i n g sex differences in fuel metabolism a n d the m e c h a n i s m s b e h i n d this m i g h t therefore help us to understand w h y w o m e n to some extent are protected against metabolic disorders a n d cardiovascular disease. We have recently described the utility of gene arrays to identify sexrelated gene products in rat liver. Here we have extended this initial study to include sex-dependent transcript profiles from rat, mouse, a n d h u m a n liver. The online software DAVID was used to classify the obtained profiles into functional groups. Regardless of species, 15% of the genes represented o n the arrays were expressed a n d roughly 15% of those were sex-differentiated. Some interesting functional groups were identified, such as lipid metabolism, insulin signaling, a n d i m m u n e responses. W i t h i n these functional groups of transcripts, specific genes with a sex-differentiated expression in all three species were identified. It seems likely t h a t sets of genes from specific metabolic pathways m a y be regulated in a coordinated manner. Identification of prom o t e r sequences a n d cis-regulatory elements shared by this set of co-regulated genes m i g h t lead to the characterization of c o m m o n l y used transcription factors a n d upstream signaling pathways.
15
Gender Mainstreaming in Health Care: Will It Stop Bias? Alice C h w o s t a l ; Angelika Bader2; Doris Musshauserl; a n d M a r g a r e t h e H o c h l e i t n e r 3
iLudwig Boltzmann Institute for Gender Studies, Tyrol±Austria; eWomen's Health Office of the State of Tyrol, Austria; and 3Innsbruck Medical University, Tyrol' Austria Heart d e a t h is the n u m b e r - o n e killer for w o m e n a n d bias in cardiology is well documented. Can we prove a n y change due to the EU action plan o n gender mainstreaming? In 2000, we conducted a prospective study o n high-tech cardiology for Tyrol/Austria including mortality and p o p u l a t i o n statistics a n d compared these data with 1995, a year prior to gender m a i n s t r e a m i n g health-care. In Tyrol, more w o m e n t h a n m e n have died due to a cardiac d e a t h t h r o u g h o u t decades. In 1995, 1008 females a n d 875 males, a n d in 2000, 1104 females a n d 792 males were registered. In 2000, 128 (43.5%) w o m e n a n d 166 (56.5%) m e n got a pacemaker; in 1995, 96 (46.6%) w o m e n and 110 (53.4%) men. A total of 688 (32.5%) w o m e n a n d 1429 (67.5%) m e n u n d e r w e n t coronary aniography. In 1995, 332 (33.9%) women, a n d 646 (66.1%) m e n received CA. In 2000, 42 (27.5%) w o m e n a n d 157 (72.5%) m e n underwent bybass surgery; in 1995, there were 54 (33.0%) w o m e n a n d 156 (67.0%) men. The $47
GENDERMEDICINE
demographic data show hardly any change; however, the mortality statistics show an increase of 9.5% for female heart deaths, but a decrease of 9.5% in males. In conclusion, all interventions show a decrease in females percentage and worst of all, we see a remarkable increase in female heart deaths. Although the coronary angiography capacity was doubled between 1995 and 2000 and the n u m b e r of coronary angiographies increased also in women, the bias against w o m e n was even worse. So these data demonstrate no benefit for w o m e n at all. Of course, sociopsychological changes need m u c h longer t h a n five years. So let's hope for the best!
16 Gender Differences in the Relation Between Ambulatory Blood Pressure and Left Ventricular Mass in Hypertensive Outpatients Franco Cipollini2; Flavia Franconil; Carlo Porta2; Enrica Arcangeli2; a n d Giuseppe Seghieri 2
iDept. Scienze del Farmaco-universita di Sassari, Italy; and 2Centroper l'ipertensione, Spedali Riuniti, Pistoia, Italy B a c k g r o u n d a n d Aims: Since gender seems to have a role in modulating the relation between hypertension and left ventricular hypertrophy (LVH), the aim of this study was to investigate whether left ventricular mass (LVM) is differently related to blood pressure (BP) in male compared to female patients. P a t i e n t s a n d M e t h o d s : We monitored 24-h ambulatory BP and measured LVM (by echographic method) in 151 (81M/70F) patients, consecutively referred to our unit to confirm hypertension or to modify therapy. Results: Twenty-four-hour systolic BP was similar in men, and in preor postmenopausal women, while 24-h diastolic BP was lower and pulse BP higher in postmenopausal women. LVH prevalence was highest in postmenopausal women, and LVM weighted more in n o n dippers t h a n in dippers in m e n (P = 0.008), in postmenopausal (P = 0.0004), but n o t premenopausal women. Percentage of LVM variance explained by systolic and diastolic BP was h i g h e r a m o n g premenopausal women, while 24-h pulse BP was about 5- to 6-fold more predictive of LVM variance in women. For every 1-mm Hg increase in either mean 24-h systolic- or pulse-BP the adjusted relative risk for LVH was 2- to 3-fold higher in w o m e n t h a n in men. Nondippers had a higher adjusted relative risk for LVH only in w o m e n (OR 7.88; 95% CI 1.37-45.4 in women; OR 2.47; 95% CI 0.67-9.13 in men). C o n c l u s i o n s : Gender is an important modulator of LVM dependence by BP. Pulse BP is a strong i n d e p e n d e n t predictor of LVM, especially and specifically in women, either prior to or after menopause, while n o n dippers are associated with LVH a m o n g women, stressing once again their different response to a same long-acting blood BP load. 17
Gender Specific Differences in Left Ventricular Hypertrophy in DOCA-Salt Mice With Hypertensive Kidney Disease Aysun Karatasl; Melina Nieminen-Kelha2; M a x i m Krikov3; Yvonne Linde2; Bjorn Hegner2; a n d Duska Dragun 2
iDepartment of Nephrology and Center for Cardiovascular Research (CCR), University Hospital Charite Campus Mitre, Berlin, Germany; 2Department of Nephrology, UniversityHospital Charite Campus Mitre, Berlin, Germany; and 3Institute of $48
Toxikology and Pharmakology, Center for Cardiovascular Research (CCR), Charite Campus Mitre, Berlin, Germany In chronic renal failure, volume overload and hypertension due to aldosterone excess lead to combination of concentric and eccentric hypertrophy. Deoxycorticosterone acetate (DOCA) mimics aldosterone by stimulation of sodium reabsorbtion in the kidney collecting ducts. Consequently, mice develop renal disease and left ventricular hypertrophy within 3-6 weeks. Signaling by the calcium-dependent phosphatase calcineurin contributes to cardiac hypertrophy in response to pathologic stimuli. Whether or not activation of calcineurin-signaling displays gender-specific differences has not been investigated yet. We hypothesized that putative gender differences in the activation of calcineurin-signaling in DOCA-salt model are estrogen dependent and mediated through estrogen-receptors. In order to differentiate blood pressure-dependent from independent effects, we will employ pharmacological intervention with hydralazine. DOCA pellets were implanted to uninephrectomized female and male C57BL/6J mice receiving a high salt diet. Blood pressure and urinary excretion were monitored weekly. At the endpoints, after 3 or 6 weeks the invasive blood pressure measurement was performed and hearts and kidneys were harvested. We studied structural and molecular markers of cardiac and renal hypertrophy and fibrosis. We preliminarily show that DOCA-salt induces volume overload and hypertension in a gender independent manner. Yet, female mice display a trend of increased renal and decreased cardiac hypertrophy implicating better adaptation to injurious stimulus. Hearts and kidneys show signs of beginning fibrosis and glomerulosclerosis in a gender dependent manner. Further experiments are directed to investigate gender specificity in the calcineurin pathway and the role of estrogen receptors.
18
Dopamine D1 Receptor Involvement in the Antidepressant-like Effect of AIIopregnanolone in the Forced Swimming Test Paolo S. D'Aquila; Marco Sardella; Maria E. Canu; Davide Carta; G i u s e p p i n a M o n n i ; Serra Gino; a n d Flavia F r a n c o n i
Dipartimento di Scienze del Farmaco, Universita di Sassari, Italy Women are more susceptible than m e n to major depression and may develop mood disturbances related to their reproductive cycle. Among the factors that may account for such gender difference, neurosteroids seem to play a major role. Evidence has been produced showing the involvement of neurosteroids, and in particular of allopregnanolone, both in the mechanism of action of antidepressants and in depressive-like behavior in animal models. Previous studies performed in male subjects have shown that dopamine D1 receptor stimulation results in an antidepressant-like effect and is critical for the expression of the effect of antidepressant drugs in the forced swimming model of depression. In the present study we examined, in Sprague-Dawley female rats, the effect of the dopamine D1 receptor antagonist SCH 23390 (0.01 and 0.025 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the forced swimming test. Since in preliminary experiments we failed to show in this strain of rats any difference in this test related to the phase of oeslxous cycle both in basal conditions and after allopregnanolone adminislxation, the subjects were tested regardless of their oes~us cycle