Psychopharmacology Research Group » Research » Current Research

Ongoing Main Projects

Sex differences in stress and depression: preclinical and clinical studies

Depression is twice more common in women than men, whereas there is evidence for sex differences in antidepressant drug response. Preclinical research that aims to improve antidepressant treatments, should use animal models validated for both sexes (Kokras and Dalla 2014). Our group has studied sex differences in models of depression and antidepressant activity since 2000. We have concluded that preclinical sex differences could have important implications for clinical research (Kokras and Dalla 2017). We have shown that female rats demonstrate enhanced immobility than males in the Forced Swim Test (FST), which is a test commonly used for screening of new antidepressants. Marked sex differences are also observed in the behavior of head swinging in the FST, with females exhibiting lower counts than males. This behavioral index might prove to be important for studying sex differences in antidepressant response (Kokras et al. 2016). Sex differences with several classes of antidepressants have been identified in behavioral, neurochemical and molecular level. Overall, our studies highlight the importance of inclusion of both male and female animals in preclinical research for depression and antidepressant response. 

Related project: “Sex differences in pharmacokinetic/pharmacodynamic interactions of antidepressant drugs”, funded by the State Scholarship foundation (IKY), 2020-2022.  

Estrogen effects in animal models of depression

We have been investigating the behavioral, neurochemical and hormonal effects of aromatase inhibitors (i.e. letrozole) in rat models of depression. Specifically, when subacute letrozole treatment was studied in the forced swim test (FST), which is a test of antidepressant potential in cycling female rats, immobility duration was reduced indicating letrozole’s antidepressant potential. Instead, aromatase inhibition for one week did not show an antidepressant response (Kokras eta la 2014). Recent findings concern letrozole effects on gonadectomized male and female rats. In these studies,  neurochemical analysis showed that aromatase inhibition decreased noradrenaline levels and dopaminergic ratios in the hippocampus and prefrontal cortex of male and female rats, irrespectively of gonadectomy. These findings indicate that aromatase inhibitors might have psychotropic attributes that depend on treatment duration.

This project took place in collaboration with Dr. Charlotte Cornil, University of Liege. Dr. Nikolaos Pastromas has recently completed his PhD thesis, under the supervision of Assoc. Prof. Christina Dalla, concerning sex differences in the role of estrogens derived from the gonads and the brain in animal models of depression.

Related current project: “GPER1 neuroestrogen membrane receptor: a novel, rapid-acting, promising target for psychopharmacology”, funded by the Hellenic Foundation for Research and Innovation (ELIDEK), Greece 2020-2023. 

The role of the thalamic nucleus reuniens in models of depression

Recent data suggest that the thalamic reuniens (RE) plays a significant role in depression (published at Mol. Psychiatry). Lesion and inactivation studies have shown that the integrity of the circuit hippocampus – prefrontal cortex (PFC) is necessary for the expression of passive (depressive) behaviors in the forced swim test in both sexes. Moreover, when RE is lesioned, male rats do not exhibit a reduction in anhedonic behavior, evident as decreased sucrose intake in the chronic mild stress (CMS). The CMS-induced alterations in neuroplasticity indices, such as decreased spine density and dendritic neuronal length in the PFC and the hippocampus are prevented in lesioned male rats. This project was in collaboration with the ICVS Institute, University of Minho in Portugal and was supported by an IBRO short-stay award. 

Ongoing collaborative projects

Erasmus+ project entitled: “Sharing Good Practices for Brain Education in Europe” (Share4Brain) granted to the Belgian Brain Council, the National Kapodistrian University of Athens and other partners, funded by the European Union, Horizon 2020, 2019-2021. 

Module coordinators at the project entitled: “Addressing Sex as a Biological Variable in Preclinical Pharmacology and Neuroscience Research: Accounting for Neglected Factors and Applying Practical Solutions to Enhance Rigor and Reproducibility?” granted to Cohen Veterans Bioscience and European College of Neuropsychopharmacology Preclinical Data Forum Network, funded by the National Institute of Health, USA 2019-2022. 

WP Leaders at PEERS (Internet platform for preclinical research standardization) granted to Cohen Veterans Bioscience and European College of Neuropsychopharmacology Preclinical Data Forum Network and funded by Cohen Veterans Biosciences, USA, 2020. 

Other projects:

  • Behavioral and neurochemical profile of the neuroactive compound BNN. In collaboration with Prof. A. Gravanis and Assoc. Prof. I. Charalampopoulos, University of Crete.
  • Pharmacological screening of the natural compound TC4 derived from Crocus Sativus. In collaboration with Prof. A. Tsarbopoulos.
  • Development of research infrastructure and software related to animal behavior (home cage activity, ultrasonic vocalizations e.t.c.). In collaboration with software developers and engineers.
  • Neurotransmitter analysis in Alzheimer's disease animal models. In collaboration with Dr. I. Sotiropoulos at the ICVS, University of Minho, Portugal.
  • Neurotransmitter analysis in rat models of drug abuse. In collaboration with Prof. K. Antoniou, University of Ioannina.

More information on national and international collaborators 

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