Department of Behavioral Neuroscience & Drug Development

Department of Behavioral Neuroscience and Drug Development has had accreditation for the EQIPD (Enhancing Quality In Preclinical Data) quality system since November, 2021. This non-GLP quality system - see the paper aims to optimize the robustness and reliability of preclinical biomedical research.  Department of Behavioral Neuroscience and Drug Development, one of EQIPD’s stakeholders was commended, inter alia, for the systematic approaches for planning and documentation of standardized research studies, and the highest culture of performing experiments.

Description

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.


Research methods

- 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
- The continued need for animals to advance brain research.
Judith R Homberg, Roger A H Adan, Natalia Alenina, Antonis Asiminas, Michael Bader, Tom Beckers, Denovan P Begg, Arjan Blokland, Marilise E Burger, Gertjan van Dijk, Ulrich L M Eisel, Ype Elgersma, Bernhard Englitz, Antonio Fernandez-Ruiz, Carlos P Fitzsimons, Anne-Marie van Dam, Peter Gass, Joanes Grandjean, Robbert Havekes, Marloes J A G Henckens, Christiane Herden, Roelof A Hut, Wendy Jarrett, Kate Jeffrey, Daniela Jezova, Andries Kalsbeek, Maarten Kamermans, Martien J Kas, Nael Nadif Kasri, Amanda J Kiliaan, Sharon M Kolk, Aniko Korosi, S Mechiel Korte, Tamas Kozicz, Steven A Kushner, Kirk Leech, Klaus-Peter Lesch, Heidi Lesscher, Paul J Lucassen, Anita Luthi, Liya Ma, Anne S Mallien, Peter Meerlo, Jorge F Mejias, Frank J Meye, Anna S Mitchell, Joram D Mul, Umberto Olcese, Azahara Oliva González, Jocelien D A Olivier, Massimo Pasqualetti, Cyriel M A Pennartz, Piotr Popik, Jos Prickaerts, Liset M de la Prida, Sidarta Ribeiro, Benno Roozendaal, Janine I Rossato, Ali-Akbar Salari, Regien G Schoemaker, August B Smit, Louk J M J Vanderschuren, Tomonori Takeuchi, Rixt van der Veen, Marten P Smidt, Vladyslav V Vyazovskiy, Maximilian Wiesmann, Corette J Wierenga, Bella Williams, Ingo Willuhn, Markus Wöhr, Monique Wolvekamp, Eddy A van der Zee, Lisa Genzel 

- Introduction to the EQIPD quality system. Anton Bespalov, René Bernard, Anja Gilis, Björn Gerlach, Javier Guillén, Vincent Castagné, Isabel A Lefevre, Fiona Ducrey, Lee Monk, Sandrine Bongiovanni, Bruce Altevogt, María Arroyo-Araujo, Lior Bikovski, Natasja de Bruin, Esmeralda Castaños-Vélez, Alexander Dityatev, Christoph H Emmerich, Raafat Fares, Chantelle Ferland-Beckham, Christelle Froger-Colléaux, Valerie Gailus-Durner, Sabine M Hölter, Martine Cj Hofmann, Patricia Kabitzke, Martien Jh Kas, Claudia Kurreck, Paul Moser, Malgorzata Pietraszek, Piotr Popik, Heidrun Potschka, Ernesto Prado Montes de Oca, Leonardo Restivo, Gernot Riedel, Merel Ritskes-Hoitinga, Janko Samardzic, Michael Schunn, Claudia Stöger, Vootele Voikar, Jan Vollert, Kimberley E Wever, Kathleen Wuyts, Malcolm R MacLeod, Ulrich Dirnagl, Thomas Steckler

- 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 this 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
Hołuj Gosia, PhD                   1998-2020
Kozela Ewa, PhD                   1998-2006
Kos Tomasz, PhD                  2003-2017
Krawczyk Martyna, M.Sc.     2004-2007
Krawczyk Martyna, M.Sc.     2017-2020
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


More publications
  • , 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.
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Head

Professor Piotr Popik, PhD

Phone number: +48 12 6623375
E-mail: popikp@if-pan.krakow.pl

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