Laboratory of Behavioral Pharmacology
Research profile
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.
Research methods
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.
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Behavioral and molecular effects of the antipsychotic drug blonanserin in the chronic mild stress model.
Maria Serena Paladini, Vittoria Spero, Veronica Begni, Francesca Marchisella, Alice Guidi, Piotr Gruca, Magdalena Lason, Ewa Litwa, Maurisz Papp, Marco A Riva, Raffaella Molteni
Pharmacological research, S1043-6618(20)31638-8 10.1016/j.phrs.2020.105330
PMID:33276101 -
AMPA receptors mediate the pro-cognitive effects of electrical and optogenetic stimulation of the medial prefrontal cortex in antidepressant non-responsive Wistar-Kyoto rats.
Mariusz Papp, Piotr Gruca, Magdalena Lason, Ewa Litwa, Wojciech Solecki, Paul Willner
Journal of psychopharmacology (Oxford, England), 10.1177/0269881120967857
PMID:33200659 -
Effect of lurasidone treatment on chronic mild stress-induced behavioural deficits in male rats: The potential role for glucocorticoid receptor signalling.
Francesca Calabrese, Paola Brivio, Giulia Sbrini, Piotr Gruca, Magdalena Lason, Ewa Litwa, Monika Niemczyk, Mariusz Papp, Marco A Riva
Journal of psychopharmacology (Oxford, England), 10.1177/0269881119895547
PMID:31913065 -
Effects on brain-derived neurotrophic factor signalling of chronic mild stress, chronic risperidone and acute intracranial dopamine receptor challenges.
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Ewa Litwa, Monika Niemczyk, Katarzyna Tota-Glowczyk, Agata Faron-Gorecka, Maciej Kusmider, Joanna Solich, Marta Szlachta, Paul Willner
Behavioural pharmacology, 10.1097/FBP.0000000000000392
PMID:29537988 -
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
PMID:30204592 -
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
PMID:30182787 -
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
PMID:27759570 -
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
PMID:28935656 -
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
PMID:28769796 -
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
Psychopharmacology, 10.1007/s00213-017-4651-4
PMID:28567697 -
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
PMID:28433460 -
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
PMID:28336340 -
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
PMID:28094500 -
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
Current neuropharmacology,
PMID:26769224 -
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
PMID:28063309
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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
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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