Publications by Year: 2012

2012
Kokras N, Dalla C, Sideris AC, Dendi A, Mikail HG, Antoniou K, Papadopoulou-Daifoti Z. Behavioral sexual dimorphism in models of anxiety and depression due to changes in HPA axis activity. Neuropharmacology 2012;62:436-45.Abstract
Anxiety and depression are considered as stress-related disorders, which present considerable sex differentiation. In animal models of anxiety and depression sex differences have been described and linked to the sexually dimorphic hypothalamus-pituitary-adrenals (HPA) axis. The present study aimed to adjust corticosterone, the main HPA axis stress hormone, in male and female adrenalectomized rats with oral (25 μg/ml) corticosterone replacement (ADXR). Subsequently we investigated the behavioral performance of ADXR rats in the open field, light/dark and forced swim test (FST). Male ADXR rats showed less anxiety-like behavior when compared to sham-operated controls, despite adequate corticosterone replacement. They further showed increased swimming and reduced climbing behavior in the FST, while immobility duration did not differ from sham-operated males. On the contrary, adrenalectomy and corticosterone replacement did not have significant effects on the female behavioral response. Females were generally more active and presented less anxiety-like behavior than males, while they exhibited higher depressive-like symptomatology in the FST. ADXR affected behavioral responses predominantly in males, which in turn modified sex differences in the behavioral profile. Females in proestrous and estrous did not differ from females in diestrous and methestrous in any measured behavioral response. Present results suggest that the male and not the female behavioral responses in models of anxiety and depression were mainly affected by ADXR. These findings may play a significant role in explaining the differential coping strategy of the two sexes in response to stressful experiences. This article is part of a Special Issue entitled 'Anxiety and Depression'.
Kouzoupis AV, Lyrakos D, Kokras N, Panagiotarakou M, Syrigos KN, Papadimitriou GN. Dysfunctional remembered parenting in oncology outpatients affects psychological distress symptoms in a gender-specific manner. Stress Health 2012;28:381-8.Abstract
Evidence suggests that gender differences appear in a variety of biological and psychological responses to stress and perhaps in coping with acute and chronic illness as well. Dysfunctional parenting is also thought to be involved in the process of coping with stress and illness; hence, the present study aimed to verify whether dysfunctional remembered parenting would influence psychological distress in a gender-specific manner in patients suffering from cancer. Patients attending an outpatient oncology clinic completed the Remembered Relationships with Parents (RRP), Hospital Anxiety and Depression and Spielberger's State-Trait Anxiety Inventory scales and the National Cancer Center Network Distress Thermometer. Although no baseline gender differences were detected, a multivariate analysis confirmed that anxiety and depression symptoms of men and women suffering from cancer are differentially affected by the RRP Control and Alienation scores. Women with remembered parental alienation and overprotection showed significantly more anxiety symptoms than men, whereas men were more vulnerable to remembered alienation than overprotection with regard to the Distress Thermometer scores. These results suggest that remembered dysfunctional parenting is crucially, and in a gender-specific manner, involved in the coping strategy adopted by male and female cancer patients.
Mikail HG, Dalla C, Kokras N, Kafetzopoulos V, Papadopoulou-Daifoti Z. Sertraline behavioral response associates closer and dose-dependently with cortical rather than hippocampal serotonergic activity in the rat forced swim stress. Physiol Behav 2012;107:201-6.Abstract
The rat Forced Swim Test (FST) is widely used to investigate the response to antidepressant treatment. Selective serotonin reuptake inhibitors (SSRIs) elongate swimming duration during the FST, while climbing duration is unaffected. In the present study, we aimed to correlate behavioral effects of the SSRI sertraline in the FST with respective changes in the serotonergic activity of the hippocampus and the prefrontal cortex. Male rats were subjected to the standard FST (two swim sessions in two consecutive days) and between the two sessions they received three i.p. injections of sertraline (10 mg/kg or 40 mg/kg) or vehicle. All rats were killed immediately after the second FST session. Unstressed animals received the same administration schemes and were killed in equivalent time-points. Serotonin and its metabolite 5-HIAA were assayed in the hippocampus and the prefrontal cortex with the use of high-performance liquid chromatography (HPLC-ED) and their ratio 5-HIAA/5-HT was calculated. Sertraline enhanced swimming and decreased immobility duration at both doses. Serotonergic activity was not altered by the 2-day swim stress in either brain region, while subchronic sertraline treatment enhanced 5-HT levels and decreased 5-HIAA/5-HT in the hippocampus and the prefrontal cortex. The serotonin turnover rate (5-HIAA/5-HT ratio) decrease is probably indicative of reduced 5-HT metabolism, as a result of 5-HT reuptake inhibition. This effect was significant in the prefrontal cortex of unstressed rats only after a higher dose of sertraline. In the prefrontal cortex, but not in the hippocampus, immobility duration was negatively correlated with 5-HT tissue levels, whereas swimming duration was positively correlated with 5-HT. These results indicate that after antidepressant treatment, behavior during the FST can be predictive of respective serotonergic changes, especially in the prefrontal cortex.