Laboratory of Behavioral Pharmacology
In the Behavioural Pharmacology Laboratory we conduct behavioural studies on the role of chronic stress in aetiology of neuropsychiatric diseases (depression, treatment-resistant depression, schizophrenia). With the use of a Chronic Mild Stress model of depression, we also do a basic research on identification of new, potential antidepressants and other non-pharmacological (eg. Deep Brain Stimulation) treatments for depression. Finally, we investigate mechanisms of coexistence of anhedonia, anxiety, cognitive disorders, drug addictions and depression in animals.
In our behavioural studies we employ Wistar and/or Wistar-Kyoto rats. Our methodology includes the following models and tests:
- Models of depression: Chronic Mild Stress, Forced Swim test, Olfactory Bulbectom, Deep Brain Stimulation and Optogenetic stimulation and inhibition in animal models of treatment-resistant depression
- Models of anxiety: Open Field, Elevated Plus-Maze, Vogel's test, Spontaneous Alternation test
- Models of cognitive deficits: Novel Object Recognition, Delayed Spatial Alternation test
- Brain reward system: Sucrose consumption test, Conditioned Place Preference and Aversion
- Dependence and drug abuse: measures of physical and psychological dependence, precipitated and conditioned withdrawal effects, withdrawal- and cue-induced place aversions
The most important recent discoveries
- Demonstrating that, in the CMS model of depression, repeated administration of compounds with different pharmacological profiles cause effects similar to those observed after traditional antidepressants, with significant faster onset of action. Two of the compounds tested in this procedure, (agomelatine, escitalopram), are now officially registered and used to treat depression in humans, and the next few ones are in the clinical trial phase.
- Demonstration that repeated administrations of rivastigmine, donepezil and ketamine, but not memantine, reverse the CMS-induced anhedonia, anxiety and cognitive deficits.
Demonstration that the CMS procedure causes impairments similar to those observed obsessive-compulsive disease (OCD) in humans. These effects are mediated by the dopaminergic D2 and D3 receptors in the nucleus accumbens septi and are normalized by a repeated administration of SSRIs but not imipramine.
- Demonstration that the CMS procedure accelerates the development of dependence on various addictive substances (morphine, nicotine, diazepam) and enhances physical and motivational withdrawal symptoms in addicted animals. These effects are normalized by repeated administration of SSRIs.
- Demonstration that Deep Brain Stimulation (DBS) in ventro-medial prefrontal cortex reverses the CMS-induced anhedonia, anxiety and cognitive deficits in two animal models of drug-resistant depression, and presenting evidence that these effects are not mediated by the dopaminergic D1, D2 and D3 receptors.
Validation of chronic mild stress in the Wistar-Kyoto rat as an animal model of treatment-resistant depression.
Paul Willner, Piotr Gruca, Magdalena Lason, Katarzyna Tota-Glowczyk, Ewa Litwa, Monika Niemczyk, Mariusz Papp
Behavioural pharmacology, 10.1097/FBP.0000000000000431
Rapid antidepressant effects of deep brain stimulation of the pre-frontal cortex in an animal model of treatment-resistant depression.
Mariusz Papp, Piotr Gruca, Magdalena Lason, Katarzyna Tota-Glowczyk, Monika Niemczyk, Ewa Litwa, Paul Willner
Journal of psychopharmacology (Oxford, England), 10.1177/0269881118791737
Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression.
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Behavioural pharmacology, 10.1097/FBP.0000000000000259
The Effect of Chronic Treatment with Lurasidone on Rat Liver Cytochrome P450 Expression and Activity in the Chronic Mild Stress Model of Depression.
Marta Kot, Anna Haduch, Mariusz Papp, Władysława A Daniel
Drug metabolism and disposition: the biological fate of chemicals, 10.1124/dmd.117.077826
S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms.
Indira Mendez-David, Jean-Philippe Guilloux, Mariusz Papp, Laurent Tritschler, Elisabeth Mocaer, Alain M Gardier, Sylvie Bretin, Denis J David
Frontiers in pharmacology, 10.3389/fphar.2017.00462
Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment`.
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Ewa Litwa, Monika Niemczyk, Katarzyna Tota-Glowczyk, Paul Willner
Stimulatory effect of desipramine on lung metastases of adenocarcinoma MADB 106 in stress highly-sensitive and stress non-reactive rats.
Beata Grygier, Marta Kubera, Danuta Wrona, Adam Roman, Agnieszka Basta-Kaim, Piotr Gruca, Mariusz Papp, Zofia Rogoz, Monika Leskiewicz, Boguslawa Budziszewska, Magdalena Regulska, Barbara Korzeniak, Katarzyna Curzytek, Katarzyna Glombik, Joanna Slusarczyk, Michael Maes, Wladyslaw Lason
Progress in neuro-psychopharmacology & biological psychiatry, S0278-5846(17)30063-5 10.1016/j.pnpbp.2017.04.024
Basal prolactin levels in rat plasma correlates with response to antidepressant treatment in animal model of depression.
A Faron-Górecka, M Kuśmider, K Szafran-Pilch, M Kolasa, D Żurawek, P Gruca, M Papp, J Solich, P Pabian, M Dziedzicka-Wasylewska
Neuroscience letters, S0304-3940(17)30254-9 10.1016/j.neulet.2017.03.034
Chronic Mild Stress-Induced Alterations of Local Protein Synthesis: A Role for Cognitive Impairment.
Francesca Calabrese, Paola Brivio, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Mariusz Papp, Marco A Riva
ACS chemical neuroscience, 10.1021/acschemneuro.6b00392
Involvement of GABAB Receptor Signaling in Antipsychotic-like Action of the Novel Orthosteric Agonist of the mGlu4 Receptor, LSP4-2022.
Monika Woźniak, Francine Acher, Marcin Marciniak, Magdalena Lasoń-Tyburkiewicz, Piotr Gruca, Mariusz Papp, Andrzej Pilc, Joanna M Wierońska
Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model.
J Depciuch, M Sowa-Kucma, G Nowak, M Papp, P Gruca, P Misztak, M Parlinska-Wojtan
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, S1386-1425(16)30722-3 10.1016/j.saa.2016.12.007
Reciprocal MicroRNA Expression in Mesocortical Circuit and Its Interplay with Serotonin Transporter Define Resilient Rats in the Chronic Mild Stress.
Dariusz Zurawek, Maciej Kusmider, Agata Faron-Gorecka, Piotr Gruca, Paulina Pabian, Joanna Solich, Magdalena Kolasa, Mariusz Papp, Marta Dziedzicka-Wasylewska
Molecular neurobiology, 10.1007/s12035-016-0107-9
The Effect of Chronic Mild Stress and Imipramine on the Markers of Oxidative Stress and Antioxidant System in Rat Liver.
Weronika Duda, Katarzyna Curzytek, Marta Kubera, Małgorzata Iciek, Danuta Kowalczyk-Pachel, Anna Bilska-Wilkosz, Elżbieta Lorenc-Koci, Monika Leśkiewicz, Agnieszka Basta-Kaim, Bogusława Budziszewska, Magdalena Regulska, Joanna Ślusarczyk, Piotr Gruca, Mariusz Papp, Michael Maes, Władysław Lasoń, Lucyna Antkiewicz-Michaluk
Neurotoxicity research, 10.1007/s12640-016-9614-8
Antidepressant, anxiolytic and procognitive effects of rivastigmine and donepezil in the chronic mild stress model in rats.
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Chronic mild stress-induced alterations of clock gene expression in rat prefrontal cortex: modulatory effects of prolonged lurasidone treatment.
Francesca Calabrese, Elisa Savino, Mariusz Papp, Raffaella Molteni, Marco A Riva
Pharmacological research, 10.1016/j.phrs.2015.12.023 S1043-6618(15)30086-4
Pharmacological and optogenetic investigation of the mechanism of action of Deep Brain Stimulation of the ventromedial prefrontal cortex in an animal model of treatmentresistant depression, Professor Mariusz Papp, PhD
NCN grant no: 2017/25/B/NZ7/02710
Investigation of the effects and mechanisms of action of Deep Brain Stimulation in two animal models of treatment-resistant depression., Professor Mariusz Papp, PhD
NCN grant no: 2015/17/B/NZ7/02979
The effect of imipramine and risperidone on regulation of the chronic mild stressinduced anhedonia and memory impairment by the limbic D1, D2 and D3 receptors in rats, Professor Mariusz Papp, PhD
NCN grant no: 2013/09/B/NZ7/04098