Medical School
Psychopharmacology Research Group
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.
Estrogen effects in animal models of depression
Our lab investigates the role of estrogens and estrogen-related pathways in mood regulation, focusing on their behavioral, neurochemical, and immunological effects in animal models of depression. Two complementary lines of research explore how modulation of estrogen synthesis and estrogen receptor activity can influence depressive phenotypes in a sex-informed manner.
Aromatase Inhibition and Estrogen Synthesis
We have been exploring the behavioral and neurochemical consequences of inhibiting estrogen synthesis using aromatase inhibitors such as letrozole. In cycling female rats, subacute letrozole administration reduced immobility in the forced swim test (FST), suggesting antidepressant-like effects. However, one-week treatment failed to produce similar outcomes, highlighting the importance of treatment duration (Kokras et al., 2014). More recent studies extended this work to gonadectomized male and female rats. Neurochemical analyses revealed that letrozole decreased noradrenaline levels and altered dopaminergic turnover in the hippocampus and prefrontal cortex of both sexes, regardless of gonadal status. These findings suggest that aromatase inhibitors may exert psychotropic effects through complex, time- and sex-dependent mechanisms.
GPER1: A Novel Estrogen Receptor Target
In parallel, we are investigating the rapid antidepressant potential of activating the G protein-coupled estrogen receptor 1 (GPER1), a recently characterized membrane-bound estrogen receptor. Ongoing studies aim to validate GPER1 as a novel, rapid, effective, and safe treatment target for female depression. We use brain-specific genetic overexpression and pharmacological activation and chronic mild stress model to examine behavioral and molecular outcomes in both sexes.
Together, these projects seek to expand our understanding of estrogen-mediated mechanisms in depression and to identify new, sex-informed therapeutic strategies that address unmet needs in mental health treatment.
Ongoing collaborative projects
Psychedelic renaissance: turn on, tune in and drop in
Funder: European Cooperation in Science and Technology, COST actions - CA24130
European Initiative to Enhance the Current SABV Policy in Preclinical Biomedical Research (EU-SABV)
Funder: European Cooperation in Science and Technology, COST actions - CA24168
INTEGRATE – Interdisciplinary Network for Training, Education, and Growing Research into Applications of and Therapeutic Expertise around Psychedelics
In collaboration with Prof. Robert Schoevers, University Medical Center Groningen (UMCG), The Netherlands. 2026–2030. Funder: European Commission – Horizon Europe Programme, Marie Skłodowska-Curie Doctoral Networks.
OPIoid-induced AUTOphagy, NEUronal plasticity and stress-related behavioural Disorders
In collaboration with Dr. Iro Georgousi, NCSR Demokritos, Greece. 2024–2025. Funder: Hellenic Foundation for Research and Innovation (H.F.R.I.).
Nutritional supplements with anti-anxiety and anti-depressant properties from Greek medicinal plants
In collaboration with Dr. Iro Georgousi, NCSR Demokritos, Greece. 2023-2024. Funder: Municipality of Attica, Greece.
Preclinical assessments of canabinoids' therapeutic efficacy in the Fmr1 KO rat model of autism, CANNABinAutism
In collaboration with Prof. K. Antoniou, University of Ioannina, Greece. 2020-2022. Funder: General Secretariat for Research and Innovation, Ministry of Development Hellenic Republic, and co-funded by the European Union.
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