Gender differences of acute and chronic administration of dehydroepiandrosterone in rats submitted to the forced swimming test

Andrade, Sabrina Chapuis de; Silveira, S.L.; Gomez, Rosane; Barros, Helena Maria Tannhauser; Ribeiro, Maria Flávia Marques

doi:10.1016/j.pnpbp.2006.12.006

Cited by 22 publications

(11 citation statements)

References 60 publications

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“…In our laboratory, we have consistently shown that female rats display higher levels of immobility during the second FST session than male rats and this is suggestive of enhanced depressive behaviour in female rats (Drossopoulou et al, 2004;Dalla et al, 2008;Pitychoutis et al, 2009;Kokras et al, 2012). However, other studies show opposite results regarding immobility levels (Alonso et al, 1991;Barros and Ferigolo, 1998;Brotto et al, 2000;Brummelte et al, 2006;Martinez-Mota et al, 2011) or find no sex differences (Poltyrev et al, 2005;Andrade et al, 2007;Alves et al, 2008). Also, another behaviour that shows significant sex differences in the FST is the frequency of head swinging, with female rats exhibiting lower numbers than male rats (Barros and Ferigolo, 1998;Drossopoulou et al, 2004;Kokras et al, 2009a).…”

Section: Sex Differences In Animal Models Of Depressionmentioning

confidence: 63%

Sex differences in animal models of psychiatric disorders

Kokras

Dalla

2014

British J Pharmacology

353

187

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Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive-compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories. LINKED ARTICLESThis article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2014.171.issue-20 Abbreviations 5-HTT, 5-HT transporter; 8-OH-DPAT, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol; Akt1, V-akt murine thymoma viral oncogene homologue 1; BDNF, brain-derived neurotrophic factor; BTBR, BTBR T + tf/J; CMS, chronic mild stress; COMT, catechol-O-methyltransferase-deficient mice; CR, conditioned response; CRF, corticotrophinreleasing factor; CS, conditioned stimulus; D1 receptor, dopamine 1 receptor; D2 receptor, dopamine 2 receptor; DISC1, disrupted-in-schizophrenia 1; Ehmt1, euchromatin histone methyltransferase 1; FBGRKO, forebrain glucocorticoid type II receptor (NR3C1) knockout; FSL, flinders sensitive rat line; FST, forced swim test; GSK3, glycogen synthase kinase 3; HAB, high anxiety-related behaviour rats; ICSS, intracranial self-stimulation; LAB, low anxiety-related behaviour rats; LI, latent inhibition; Mthfr, methylenetetrahydrofolate reductase; OCD, obsessive-compulsive disorder; PPI, prepulse inhibition; PTSD, post-traumatic stress disorder; SSRI, selective 5-HT re-uptake inhibitors; US, unconditioned stimulus; WKY, Wistar Kyoto IntroductionThe total disease burden for neuropsychiatric disorders in the European Union has been recently ...

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Section: Sex Differences In Animal Models Of Depressionmentioning

confidence: 63%

Sex differences in animal models of psychiatric disorders

Kokras

Dalla

2014

British J Pharmacology

353

187

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“…Previous reports have indicated that females are more active than male rats (Dalla et al, 2008; Yang et al, 2007), male rats show more immobility than do females (Ferigolo et al, 1998; Paré and Redei, 1993), or there are no sex differences (Andrade et al, 2007; David et al, 2001). When comparisons are made between females in low P phases of the estrous cycle, such as diestrous, they typically demonstrate greater immobility than do males (Frye and Wawrzycki, 2003).…”

Section: Discussionmentioning

confidence: 93%

Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice

Frye

2011

Pharmacology Biochemistry and Behavior

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Progesterone may have actions independent of intracellular progestin receptors (PRs) to influence depressive behavior. To investigate this, we examined effects of progesterone (P; 10 mg/kg, SC) on the depressive behavior of mice in the forced swim test (FST). In Experiment 1, subjects were 4 to 6 months old, intact or ovariectomized (OVX) female and intact or gonadectomized (GDX) male, C57/BL6 mice. Progesterone reduced depressive behavior of young diestrous and OVX mice but male mice were impervious to effects of P. In Experiment 2, subjects were intact aged (20–28 months old) C57/BL6 female and male mice. Progesterone reduced depressive behavior of aged female and male C57/BL6 mice, albeit effects were greater among males. In Experiment 3, effects of P were examined in 4 to 6 months old, gonadally-intact, female and male mice that were wildtype or PR knockouts (PRKOs). Progesterone decreased depressive behavior of young adult, wildtype and PRKO mice, which showed greater immobility than did their wildtype counterparts. In Experiment 4, subjects were 18–24 months old wildtype or PRKO mice (Exp 4). Progesterone decreased immobility among wildtype and PRKO mice (which were not different in terms of their baseline depressive behavior). Together these data demonstrate that P decreases depressive behavior of young and older adult C57/BL6, wildtype and PRKO mice, which suggest that acute anti-depressant effects of P may occur independent of actions at “classic” PRs.

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“…To determine the estrous cycle of the female rats, vaginal smears were performed throughout the treatment period by a trained researcher. Only female rats that had two regular 4‐ to 5‐day cycles and were in the diestrus II phase on the day of the experiment were included in this study . This phase of the estrous cycle was chosen because it presents a hormonal correlation with the premenstrual phase in women, which in turn may be related to a higher risk for depression and because this phase was the most responsive to the progesterone treatment in a previous study performed by our group .…”

Section: Methodsmentioning

confidence: 99%

“…17,21,22 Although studies in animals are scarce, hemispheric asymmetry has also been associated with sex differences, stress, and fear behaviors. 23,24 Thus, because of the following: (i) progesterone is a neuroactive steroid with non-genomic effect on the ionotropic GABA A R; 8 (ii) fluctuations on the levels of sex hormones are related to depressive disorders in females; 8,6,25 (iii) brain hemispheric asymmetry has also been associated with depressive behaviors and sex differences; 17,20 (iv) the prefrontal cortex is a nodal point of the limbic circuit involved in the control of emotions and abnormalities in this area are associated with symptoms of depression 17,22,26 ; and (v) the diestrus phase in female rodents shows a hormonal correlation with the premenstrual phase in women, who are at a higher risk for dysphoric disorder, 4,9,17 the objective of the present study was to evaluate the effect of progesterone administration on GABA A R a1 and g2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female rats compared with male rats exposed to the forced swimming test (FST), a tool to assess antidepressant effect of drugs.…”

Section: Introductionmentioning

confidence: 99%

Effect of progesterone on the expression of GABA_A receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere

Andrade

Arbo

Batista

et al. 2012

Cell Biochemistry & Function

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Progesterone is a neuroactive hormone with non-genomic effects on GABA(A) receptors (GABA(A)R). Changes in the expression of GABA(A)R subunits are related to depressive-like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABA(A)R α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats (n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg⁻¹) or vehicle, during two complete female estrous cycles (8-10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive-like behaviors and GABA(A)R α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABA(A)R γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABA(A) system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABA(A) R α1 subunit expression in the right prefrontal cortex of female rats.

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Gender differences of acute and chronic administration of dehydroepiandrosterone in rats submitted to the forced swimming test

Cited by 22 publications

References 60 publications

Sex differences in animal models of psychiatric disorders

Sex differences in animal models of psychiatric disorders

Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice

Effect of progesterone on the expression of GABA_A receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere

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Gender differences of acute and chronic administration of dehydroepiandrosterone in rats submitted to the forced swimming test

Cited by 22 publications

References 60 publications

Sex differences in animal models of psychiatric disorders

Sex differences in animal models of psychiatric disorders

Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice

Effect of progesterone on the expression of GABAA receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere

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Effect of progesterone on the expression of GABA_A receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere