| Objective To investigate the influence of estradiol and fluoxetine on rat behavior in an animal model of depression-the forced swimming test (FST) and body weight, explore the potential antidepressant effect of estradiol by comparing with fluoxetine.Methods 42 female Sprague-Dawley rats were randomly divided into ovariectomy group and sham group, according to different drug treatment, animals were then divided into 6 groups (n=7):the ovariectomy+oil group, the ovariectomy +estradiol group, the ovariectomy+fluoxetine group, the ovariectomy+estradiol+ fluoxetine group, the sham+saline group and the sham+fluoxetine group. Three weeks after the ovariectomy and sham operation, an effective dose of estradiol (10μg·rat-1·day-1) and fluoxetine (10 mg·kg-1·day-1) were used and drugs were administered for fourteen days along with oil as control intervention. On the fourteenth day, the animals were subjected to the 15-min FST procedure and videotaped. Rat behavior was then analyzed using time-sampling technique according to the methods widely accepted. Rat body weights were recorded on alternate days.Results (1) The body weights gained during the three weeks periods before the drug treatment in the ovariectomy group [(54.3±15.1)g] was significantly higher than that in the Sham group [(30.8±11.0)g] (t=5.16, P<0.01). (2) The body weights lose during the fourteen days drug treatment periods were significantly higher in the ovariectomy+fluoxetine group [-48.0(-59.8--15.3)g] than that in the ovariectomy+ fluoxeitne+estradiol group [-5.0(-5.8-8.3)g] (H=25.96, P<0.001). (3) During the 15-min FST, immobility behavior in the ovariectomy+oil group [(55.4±10.1) counts/15 min] was significantly more than that in the ovariectomy+estradiol group [(23.6±4.4) counts/15 min], ovaricetomy+fluoxetine group [(15.7±3.7) counts/15 min], ovariecrtomy+estradiol+fluoxetine group [(15.1±3.0) counts/15 min], sham +saline group [(36.7±2.8) counts/15 min] and sham+fluoxetine group [(12.2±5.0) counts/15 min] (F5,34=62.80, P<0.001). (4) During the 15 min FST, the swimming behavior in the ovariectomy+estradiol group [(86.6±9.1) counts/15 min], ovaricetomy+fluoxetine group [(93.8±5.6) counts/15 min], ovariecrtomy+ estradiol+fluoxetine group [(94.1±8.0) counts/15 min] and sham+fluoxetine group [(98.7±14.7) counts/15 min] was significantly more than that in the ovariectomy+ oil group [(61.7±6.3) counts/15 min] (F5,34=14.47, P<0.001). (5) The immobility increased significantly during the 15-min FST procedure through three continuous 5-min part of 15 min (F2,12=62.33, P<0.001).Conclusion (1) Body weight of rats was gained significantly after ovariectomy. Fluoxetine administration significantly dropped rat body weight. Estradiol attenuates the body weight effect caused by fluoxetine administration to ovariectomized female rats. (2) In the FST, chronic administration of estradiol exhibits an antidepressant-like effect as FLX, which was evidenced by increased swimming and decreased immobility. Objective To investigate the influence of estradiol and fluoxetine with rats subjected to the forced swimming stress on 5-hydroxytryptamine neurotransmitter system (tryptophan hydroxylase,5-hydroxytryptamine content in raphe nuclei, and serotonin transporter protein,5-hydroxytryptamine 2C receptor content respectively in hippocampus, amygdala) of rat brain. Explore the antidepressant mechanism of estradiol and fluoxetine in women depression.Methods Three weeks after the ovariectomy,42 ovariectomized (OVX) female Sprague-Dawley rats were randomly divided into 6 groups (n=7) according to different treatment meausures:the ovariectomy+oil+non-stress group (oil,0.1 ml·rat-1·day-1, subcutaneous administered, s.c.), the ovariectomy+oil+stress group (oil,0.1 ml·rat-1·day-1, s.c.), the ovariectomy+estradiol+stress group (17β-estradiol benzoate,10μg·0.1ml-1·rat-1·day-1, s.c.), the ovariectomy+fluoxetine+stress group (fluoxetine,10 mg·kg-1·day-1, intraperitoneally administered, i.p.), the ovariectomy+ estradiol+fluoxetine+stress group (same dosage as above) and the sham+saline+ non-stress group. An effective dose of estradiol and fluoxetine were used and drugs were administered as single daily dose for fourteen days. On the fourteenth day, the animals were subjected to the 15-min forced swimming test (FST). Two hours after the FST, rats in each group were anesthetized and perfused with 4% paraformaldehyde for trryptophan hydroxylase,5-hydroxytryptamine, serotonin transporter and 5-hydroxytryptamine 2C receptor immunofluorescence staining. The integrated optical density of targeted antigen positive region was used as representative for the level of trryptophan hydroxylase,5-hydroxytryptamine, serotonin transporter protein and 5-hydroxytryptamine 2C receptor.Results (1) The integrated optical density in the targeted antigens positive regions in the ovariectomy+oil non-stress group does not differ from that of sham+ saline+non-stress group, which include tryptophan hydroxylase,5-hydroxytryptamine in the raphe nucleus, serotonin transporter,5-hydroxytryptamine 2C receptor in the hippocampus and amygdala (P>0.05). (2) The foced swimming stress significantly decreased the integrated optical density of tryptophan hydroxylase-and 5-hydroxytryptamine-positive regions in the raphe nuclei of female ovariectomized rats (P<0.05), while increased the integrated optical density of serotonin transporter-and 5-hydroxytryptamin-positive regions in the hippocampus CA3 region, basolateral amygdaloid nucleus (P<0.01). (3) Compared with ovariectomy+oil+stress group, it has been shown that giving estradiol, fluoxeitne and estradiol+fluoxetine combination administration in advance for fourteen days significantly increased the integrated optical density of tryptophan hydroxylase-,5-hydroxytryptamin-positive regions in the raphe nuclei, while decreased the integrated optical density of serotonin transporter-and 5-hydroxytraptamine 2C receptor-positive regions in hippocampus CA3, basolateral amygdaloid nucleus (P<0.01) of ovariectomized female rats subjected to forced swimming test.Conclusion (1) In the fifth week of ovariectomy which caused the significantly dropped gonadal hormone level, the content of tryptophan hydroxylase and 5-hydroxytryptamine in the raphe nucleus, serotonin transporter protein, 5-hydroxytryptamine 2C receptor in the hippocampus and amydala remained unchanged. (2) Forced swimming stress showed decreasing effect on tryptophan hydroxylase and 5-hydroxytryptamine content in the raphe nucleus and increasing effect on the serotonin transporter protein,5-hydroxytryptamine 2C receptor content in the hippocampus CA3 and basolateral amygdaloid nucleus. (3) Estradiol and fluoxetine given advance can prevent the changes in the serotonin system in rat brain induced by the forced swimming stress, which can increase tryptophan hydroxylase and 5-hydroxytrytamine content in the raphe nuclei and decrease serotonin transporter protein,5-hydroxytryptamine 2C receptor content in the hippocampus and basolateral amygdaloid nucleus. Combining the results in our behavior study of forced swimming test, these biochemical mechanisms may be one of the underlying antidepressant mechanisms of estradiol and fluoxetine.
|
PDF Full Text Request