Department of Behavioral Neuroscience & Drug Development
Modeling human psychological functions is a fundamental challenge in modern neurobiology and psychopharmacology. This applies both to physiological mental processes (memory, cognitive flexibility, anxiety, activity, optimism, social behavior, communication, mood and drive) and to mental disorders (depression, schizophrenia, substance dependence and behavioral addictions such as gambling).
Some of these functions cannot be studied in humans, therefore laboratory rodent tests are used.
The Department of Behavioral Neuroscience and Drug Development investigates the effects of various substances (new chemical compounds or drugs) on animal behavior. We use a variety of tests intended to evaluate the effectiveness of novel chemical formulations for memory-enhancing properties, anxiolytic activity, the ability to change individual levels of pessimism/optimism in rats and mice or to improve an animal performance on neuropsychological testing. We study rodent ultrasonic communication to assess emotional states in animals, expressed by alarm or euphoric sounds. We also investigate whether a given substance may be useful in the treatment of schizophrenia (e.g. intensifies social behavior, improves cognitive functions), depression (e.g. restores good mood, activates animals), or whether it inhibits addiction. The latter aspect is reflected by the reduced attractiveness of the cage in which the drug or alcohol was administered, or an inhibition of rats’ propensity to press the lever in the 'one-armed bandit' model.
The purpose of our research is to understand how chemicals modulate the behavior of laboratory animals. Our research is designed to develop new, effective drugs for psychiatric disorders and to understand how known drugs used in psychiatry affect the brain. The ultimate goal is to develop new therapies for mental illnesses.
- memory tests: new object recognition, Morris water maze, passive and active avoidance, Skinner instrumental cages
- neuropsychological tests: cognitive flexibility (ASST), attention (5-CSRTT)
- anxiety tests: Vogel conflict test, elevated 'plus' maze, four-plates test, open field test
- activity tests: automatic actometers, open field test
- ambiguous-cue interpretation test to measure cognitive judgement bias (optimism / pessimism)
- social interactions and social preferences tests
- system for recording, analyzing and emission ultrasonic vocalizations
- tests to assess antidepressant effects of compounds: forced swim test, sucrose preference
- models of antipsychotic drug action: sensorimotor gating test (PPI), social communication test
- models of addiction: conditional place preference and aversion test, instrumental 'one-armed bandit' gambling model and Iowa test
The most important recent discoveries
- we have shown that serotonin type 6 and 7 receptors may be responsible for some of the antipsychotic effects of drugs used in the treatment of schizophrenia (e.g. Nikiforuk et al. Effects of the selective 5-HT7 receptor antagonist SB-269970, and amisulpride on ketamine-induced schizophrenia like deficits in rats). http://journals.plos.org/2013
- using the cognitive bias test we have demonstrated in that rats that emit positive ultrasound vocalizations are optimistic (Ryguła et al. Laughing rats are optimistic). http://journals.plos.org/2012
See Wikipedia for more information about our research.
Our former students:
Adamcio Bartek, PhD 2001-2004
Bobula Bartosz, PhD 1998-1999
Fijał Katarzyna, PhD 2009-2013
Galoch Zdzisław, PhD 1998-1999
Jamroży Małgorzata, M.Sc. 2006-2007
Kozela Ewa, PhD 1998-2006
Kos Tomasz 2003-2017
Krawczyk Martyna, M.Sc. 2004-2007
Kubik Jakub, M.Sc. 2012-2014
Łopuch Sylwia, PhD 2008-2009
Pluta Helena, M.Sc. 2012-2013
Magalas Zofia, PhD 2000-2001
Rafa Dominik, M.Sc. 2010-2017
Ryguła Rafał, PhD 1999-2001
Ryguła Rafał, PhD 2013-2017
Schneider Tomasz, PhD 2004-2006
Wesołowska Anna, PhD 2007-2008
Novel non-sulfonamide 5-HT6receptor partial inverse agonist in a group of imidazo[4,5-b]pyridines with cognition enhancing properties.
David Vanda, Miroslav Soural, Vittorio Canale, Séverine Chaumont-Dubel, Grzegorz Satała, Tomasz Kos, Petr Funk, Veronika Fülöpová, Barbora Lemrová, Paulina Koczurkiewicz, Elżbieta Pękala, Andrzej J Bojarski, Piotr Popik, Philippe Marin, Paweł Zajdel
European journal of medicinal chemistry, S0223-5234(17)31084-X 10.1016/j.ejmech.2017.12.053
A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats.
Agnieszka Nikiforuk, Predrag Kalaba, Marija Ilic, Volker Korz, Vladimir Dragačević, Judith Wackerlig, Thierry Langer, Harald Höger, Joanna Golebiowska, Piotr Popik, Gert Lubec
Frontiers in behavioral neuroscience, 10.3389/fnbeh.2017.00222
Novel 5-HT7R antagonists, arylsulfonamide derivatives of (aryloxy)propyl piperidines: Add-on effect to the antidepressant activity of SSRI and DRI, and pro-cognitive profile.
Vittorio Canale, Anna Partyka, Rafał Kurczab, Martyna Krawczyk, Tomasz Kos, Grzegorz Satała, Bartłomiej Kubica, Magdalena Jastrzębska-Więsek, Anna Wesołowska, Andrzej J Bojarski, Piotr Popik, Paweł Zajdel
Bioorganic & medicinal chemistry, S0968-0896(17)30359-0 10.1016/j.bmc.2017.03.057
Lesions of the Orbitofrontal but Not Medial Prefrontal Cortex Affect Cognitive Judgment Bias in Rats.
Joanna Golebiowska, Rafal Rygula
Frontiers in behavioral neuroscience, 10.3389/fnbeh.2017.00051
Effects of acute dopaminergic and serotonergic manipulations in the ACI paradigm depend on the basal valence of cognitive judgement bias in rats.
Joanna Golebiowska, Rafal Rygula
Behavioural brain research, S0166-4328(16)31261-X 10.1016/j.bbr.2017.02.013
Stimulation of nicotinic acetylcholine alpha7 receptors rescue schizophrenia-like cognitive impairments in rats.
Agnieszka Potasiewicz, Agnieszka Nikiforuk, Małgorzata Hołuj, Piotr Popik
Journal of psychopharmacology (Oxford, England), 10.1177/0269881116675509
3-Furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic receptor, reverses schizophrenia-like cognitive and social deficits in rats.
Agnieszka Potasiewicz, Małgorzata Hołuj, Tomasz Kos, Piotr Popik, Hugo R Arias, Agnieszka Nikiforuk
Neuropharmacology, S0028-3908(16)30450-6 10.1016/j.neuropharm.2016.10.002
The combination of memantine and galantamine improves cognition in rats: The synergistic role of the α7 nicotinic acetylcholine and NMDA receptors.
Agnieszka Nikiforuk, Agnieszka Potasiewicz, Tomasz Kos, Piotr Popik
Behavioural brain research, 10.1016/j.bbr.2016.07.023 S0166-4328(16)30451-X
The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia.
Agnieszka Nikiforuk, Małgorzata Hołuj, Tomasz Kos, Piotr Popik
Neuropharmacology, 10.1016/j.neuropharm.2016.01.035 S0028-3908(16)30034-X
N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties.
Paweł Zajdel, Krzysztof Marciniec, Grzegorz Satała, Vittorio Canale, Tomasz Kos, Anna Partyka, Magdalena Jastrzębska-Więsek, Anna Wesołowska, Agnieszka Basińska-Ziobroń, Jacek Wójcikowski, Władysława A Daniel, Andrzej J Bojarski, Piotr Popik
ACS medicinal chemistry letters, 10.1021/acsmedchemlett.6b00056
The effects of PDE10 inhibition on attentional set-shifting do not depend on the activation of dopamine D1 receptors.
Agnieszka Nikiforuk, Agnieszka Potasiewicz, Dominik Rafa, Karla Drescher, Anton Bespalov, Piotr Popik
Behavioural pharmacology, 10.1097/FBP.0000000000000201
Alterations of Bio-elements, Oxidative, and Inflammatory Status in the Zinc Deficiency Model in Rats.
Urszula Doboszewska, Bernadeta Szewczyk, Magdalena Sowa-Kućma, Karolina Noworyta-Sokołowska, Paulina Misztak, Joanna Gołębiowska, Katarzyna Młyniec, Beata Ostachowicz, Mirosław Krośniak, Agnieszka Wojtanowska-Krośniak, Krystyna Gołembiowska, Marek Lankosz, Wojciech Piekoszewski, Gabriel Nowak
Neurotoxicity research, 10.1007/s12640-015-9571-7
Anandamide mediates cognitive judgement bias in rats.
J Kregiel, N Malek, P Popik, K Starowicz, R Rygula
Neuropharmacology, S0028-3908(15)30101-5 10.1016/j.neuropharm.2015.09.009
Positive allosteric modulators of alpha 7 nicotinic acetylcholine receptors reverse ketamine-induced schizophrenia-like deficits in rats.
Agnieszka Nikiforuk, Tomasz Kos, Małgorzata Hołuj, Agnieszka Potasiewicz, Piotr Popik
Neuropharmacology, S0028-3908(15)30041-1 10.1016/j.neuropharm.2015.07.034
Antidepressant-like effects of ketamine, norketamine and dehydronorketamine in forced swim test: Role of activity at NMDA receptor.
Kinga Sałat, Agata Siwek, Gabriela Starowicz, Tadeusz Librowski, Gabriel Nowak, Urszula Drabik, Ryszard Gajdosz, Piotr Popik
Neuropharmacology, 10.1016/j.neuropharm.2015.07.037 S0028-3908(15)30044-7
, Agnieszka Potasiewicz, PhD
The effects of positive allosteric modulators of alpha7 nicotinic acetylcholine receptors on complex cognitive processes, Agnieszka Nikiforuk, PhD
α7 nicotinic acetylcholine receptors (α7-nAChRs) play important role in the regulation of complex cognitive functions which may be impaired in a number of psychiatric disorders. Moreover, it has been suggested that the α7-nAChRs may be implicated in the pathogenesis of schizophrenia. Therefore, in recent years, α7-nAChRs arouse a great interest as a target for the development of pharmacological treatment of cognitive dysfunctions in schizophrenia. The activity of α7-nAChR can be modulated be either orthosteric agonists or positive allosteric modulators (PAMs). Despite numerous preclinical evidences, the procognitive action of direct α7-nAChR agonist has not been conclusively confirmed in patients with schizophrenia. Allosteric modulation is thought to be associated with more favourable and more specific action. Hence, α7-nAChR PAMs may represent more promising tool. While several α7-nAChR PAMs have been recently developed, their behavioural effects, including their potential impact on cognitive processes, have not been yet extensively characterised. Our research hypothesis is based on the presumption that the action of PAMs may differ from the effects induced by orthosteric receptor activation. It is suggested by PAM-induced retardation of rapid desensitization, a fundamental feature of α7-nAchR. Therefore, the aim of the proposed project is to examine the effects of α7-nAChR PAM in comparison to orthosteric agonists in animal tasks assessing cognitive domains that are important from the perspective of cognitive deficits encountered in schizophrenia (e.g., executive functions, attention, and working memory).
, Professor Piotr Popik, PhD
The evaluation of the efficacy of ligands of alpha7 nicotinic acetylcholine receptors in models of autism in rats, Agnieszka Nikiforuk, PhD
Autism spectrum disorders (ASD), one of the most common neurodevelopmental disorders, are now a major public health and social concern throughout the world. The ASD symptoms are grouped in two main diagnostic criteria: social/communicative deficits and restricted, repetitive patterns of behaviours. These symptoms manifest themselves at early childhood, persist into adulthood and limit or impair everyday life. ASD is also accompanied by diversity of comorbid features, as for example, anxiety, hyperactivity, impulsivity, inattention, irritability, sensory abnormalities, aggressive behaviour and cognitive deficits. One of the most troublesome aspects of ASD is that the number of patients has strikingly increased in the last years. As a consequence, costs relating to the treatment and care of ASD patients are also dramatically rising.Pharmacologic treatment of ASD is mainly targeted at co-occurring problems. Thus, there is an urgent need for a new pharmacotherapy that can effectively treat the core symptomatology of the disease, particularly in the social/communication domain. A wide body of evidence points to the role of cholinergic system, including alpha 7 nicotinic acetylcholine receptors (α7-nAChR), in the pathophysiology of ASD and pharmacotherapy of this disorder. Nevertheless, the strategy based on a direct activation of α7-nAChR has not yet been assessed for the efficacy against core symptoms of ASD in either clinical or preclinical studies. The research hypothesis of our project is that the selective targeting of α7-nAChR can address both core symptom domains and co-morbid impairments. To test this hypothesis we plan to assess the efficacy of selective α7-nAChR ligands (the agonist and positive allosteric modulators) in neurodevelopmental ASD models in rats. Behavioural studies will be complemented by the assessment of neurochemical changes. The results of the proposed study will provide a preclinical framework for targeting α7-nAChR ligand as a pharmacotherapy of ASD.
- 5 choice serial reaction time test
- active avoidance
- ambiguous-cue interpretation test
- ambiguous-cue interpretation test
- analysis of ultrasonic vocalisations
- attentional set shifting test
- behavioral sensitisation
- conditioned place preference
- discrimination tests
- eleveted zero test
- excitotoxic lesions
- forced swim test
- immobilisation stress
- Iowa test
- locomotor activity
- Morris water maze
- neurochemically specific lesions
- novel obiect recognition
- open field test
- passive avoidance
- prepulse inhibition
- rat Slot Machine Task
- reversal learning
- sexual behaviour
- social interactions
- social interactions
- spatial delayed alteration
- spontaneous alternation test
- sucrose preference test
- tail flick test
- tail suspension test
- Vogels test
- Western Blot
- allosteric modulation
- animal models
- behavioural analysis
- cognitive flexibility
- cognitive functions
- cognitive neuroscience
- drug addiction
- Executive Function
- glutamatergic receptors
- immobilization stress
- metabotropic glutamate receptors
- neurodevelopmental models
- nicotinic receptors
- NMDA receptor
- object recognition
- operant conditioning
- Pavlovian conditioning
- serotonin receptors
- social cognition
- ultrasonic vocalization
- working memory