Team II

Research profile

Recently, our research has been focused on the effects of new psychoactive substances (NPS), commonly referred to as designer drugs, on the central nervous system and their potential neurotoxic properties. These compounds  have been detected, for example, in ecstasy pills, which are used as psychostimulats mainly by young people (16-24 years old, according to the GIS [Chief Sanitary Inspectorate] data). However, in addition to psychostimulatory properties, NPS produce also a wide range of adverse reactions. It is speculated that NPS may have neurotoxic properties, that are more severe than neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) or methamphetamine. So far, we have found that single and multiple doses of NPS produce significant changes in the release of dopamine, serotonin, glutamate and γ-aminobutyric acid (GABA) in various structures of the rat brain. The above mentioned studies have been performed using microdialysis procedure in freely-moving animals and HPLC. We also measure monoamine levels in the brain to identify the deficits which are indicative of damaged nerve endings. DNA damage, determined using a comet assay, provides another progression marker of the neurodegenerative process. As a part of NPS research, our team uses also various behavioral tests. Separate ongoing research project conducted in our laboratory refers to neurotoxic effects of MDMA administered jointly with caffeine, the substance found in "party pills" used for recreational purposes. Following single and repeated administration, both substances caused drastic changes in monoamine release in mouse brain. Significant DNA damage was also observed, indicating the presence of oxidative stress. We are also involved in the collaboration with other departments in the Institute of Pharmacology. These studies include, among others, evaluation of combined antidepressant and antipsychotic treatments as a novel alternative therapy in drug-resistant depression and chronic schizophrenia. For this purpose, the release of dopamine and serotonin in the rat frontal cortex is examined. Our team also participates in the search for new antidepressants and antipsychotics within a large group of newly synthesized ligands and modulators of metabotropic glutamate receptor subtypes. Analysis of neurotransmitters is carried out using high-performance liquid chromatography (HPLC) with electrochemical, coulochemic and fluorescence detection.

Research methods:

1. Brain microdialysis in rats and mice
2. High performance liquid chromatography (HPLC) with electrochemical, coulochemical and fluorescence detection
3. Assessment of DNA damage using a comet assay
4. Behavioral tests

The most important two discoveries in the last 3 years

1. Demonstration of antioxidant and anti-inflammatory properties of A2A receptor antagonists as a new, non-dopaminergic treatment in Parkinson's disease.
2. Caffeine-induced augmentation of psychostimulant and neurotoxic effects of MDMA (ecstasy) in mice.
   

Keywords:

- dopamine, serotonin, glutamate, GABA, adenosine
- receptors and the release of neurotransmitters in vivo (microdialysis)
- new psychoactive substances (NPS)
- neurodegeneration
- neurotoxicity
- oxidative DNA damage (comet test)
- oxidative stress, free radicals
- metabotropic receptor ligands for glutamate
- antidepressants and atypical antipsychotics