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Od laboratorium do kliniki: ocena funkcji poznawczych w modelach zwierzęcych

100%
Nikiforuk A.
Wszechświat
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2016
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tom 117
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nr 01-03
2

The effect of selective 5HT2A, 5HT6 and 5HT7 receptor antagonists on ketamine-induced social deficits in rats

51%
Holuj M., Nikiforuk A., Pupik P.
Acta Neurobiologiae Experimentalis
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2014
|
tom 74
|
nr 3
Social withdrawal is one of the negative symptoms of schizophrenia, which often precedes the onset of the first psychotic episode and persists for most of patient‘s life. Current antipsychotics are relatively ineffective in normalize this social dysfunction. There are only a few studies addressing the efficacy of antipsychotic drugs in animal models of social deficits. The aim of the present study was to evaluate the effects of the selective serotonin 5HT2A, 5HT6 and 5HT7 receptor antagonists in ketamine-induced schizophrenia-like social deficit in rats. After 5 days of social isolation male Sprague-Dawley rats were individually adapted to the open field arena for 7 minutes. On the next day, two unfamiliar rats of matched body weight received the same treatment and were placed in the open field arena for 10 minutes. The active, non-agressive social behaviors were scored: sniffing, social grooming , following, mounting and climbing. Ketamine caused significant reduction of the time of active social behavior. Administration of 5HT7 but not 5HT6 or 5HT2A receptor antagonist reversed ketamine-induced social deficits. Present findings suggest the importance of 5HT7 receptor antagonism in ameliorating the negative symptoms of psychoses. It is noteworthy that most recently synthesized second and third generation antipsychotic exhibit a high, nano-molar affinity for 5HT7 receptor. Supported by the Statutory Funds of the Institute of Pharmacology, Polish Academy of Sciences.
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Social play behavior of rats in the model of autism induced by prenatal exposure to polyinosinic: polycytidylic acid

51%
Gzielo K., Holuj M., Popik P., Nikiforuk A.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
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nr Suppl.1
INTRODUCTION: Social play behavior is crucial for acquiring social skills and the development of normal socioaffective responses. The repertoire of social play in rats changes throughout the life, peaking during the juvenile period and falling off around adolescence. The most characteristic postures in social plays of rodents are pinning and pouncing. In addition to playful activities during social play, rats also engage in non-playful behaviors including social exploration. The lack of ability to engage in social play with conspecifics is the main indicator of neuropsychiatric disorders like autism. There is strong evidence suggesting that maternal infection during pregnancy is correlated with increased risk of developing autism spectrum disorder (ASD) in the child. To model maternal immune activation, polyinosinic: polycytidylic acid (poly(I:C)) is used to induce inflammatory response in the maternal-placental-fetal axis. The resulting inflammation leads to perturbation of the brain development of pups and consequently may lead to development of the symptoms of autism. AIM(S): We performed the Social Play Test to study changes in social play behavior of rats in an ASD model induced by prenatal exposure to poly(I:C). METHOD(S): Pregnant Sprague-Dawley rat dams received a single intraperitoneal injection of poly(I:C) (5 mg/kg) or vehicle at gestational day 15. The 30 – 35 days-old rats were then tested using the Social Play Test. RESULTS: Rats that were prenatally exposed to poly(I:C) demonstrated a significant decrease in a number of episodes of pinning compared to the vehicle-treat ed controls. We also observed significantly diminished time of social exploration in the offspring of poly(I:C) treated females. CONCLUSIONS: The present study demonstrated that prenatal exposure to poly(I:C) results in social deficits in juvenile rats. Measures of social play behaviours in rats could be useful for quantifying abnormal levels of sociability associated with autism. FINANCIAL SUPPORT: Supported by NSC grant: 2016/23/B/NZ7/01131.
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Activation of Alpha 7 nicotinic acetylcholine receptors against cognitive and sensorimotor gating deficits in animal model of schizophrenia

51%
Potasiewicz A., Nikiforuk A., Holuj M., Popik P.
Acta Neurobiologiae Experimentalis
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2015
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tom 75
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nr Supl.
BACKGROUND AND AIMS: Alpha 7 nicotinic acetylcholine receptors(α7 nAChRs) are involved in the regulation of cognitive processes. Furthermore, it has been suggested that α7 nAChRs might be implicated in the pathophysiology of schizophrenia. Hence, selective activation of α7 nAChRs is considered to be a potential therapeutic strategy aimed at ameliorating cognitive dysfunctions associated with schizophrenia. Preclinical data indicated that orthosteric ligands, like the partial α7 nAChR agonist, A582941, produced procognitive effects, but little is known about efficacy of this compound in animal models of schizophrenia. The aim of present study was to evaluate the efficacy of A582941 against MK-801- induced schizophrenia-like deficits in rats. Prepulse inhibition of startle response test (PPI), discrete paired-trial delayed alternation task in a T-maze and five-choice serial reaction time task (5-CSRTT) were employed in this study. RESULTS: A582941 reversed the sensorimotor gating and working memory impairment evoked by MK-801 as assessed in the PPI test and T-maze, respectively. However, this compound did not affect the rats’ attentional performance in the 5-CSRTT. CONCLUSIONS: The present study demonstrates the beneficial effects of α7 nAChRs agonist on sensorimotor gating and some aspects of cognition in rats tested in impaired conditions. Therefore, our results support the notion that α7 nAChRs may constitute a useful targets for procognitive therapy in schizophrenia. This study was supported by the Polish National Science Centre grant NCN 2012/07/B/NZ/01150 and statutory funds from the Institute of Pharmacology, Polish Academy of Sciences (Krakow, Poland). Agnieszka Potasiewicz is a holder of scholarship from the KNOW sponsored by Ministry of Science and Higher Education, Republic of Poland.
5

Time-related discriminatory stimulus following LSD administration in rats

51%
Kuziak A., Krawczyk M., Nikiforuk A., Popik P.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
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nr Suppl.1
INTRODUCTION: Drug discrimination is an important technique in behavioral pharmacology since the last 40 years. LSD affects multiple receptor subtypes of the serotonergic system and is one of the most powerful agents producing psychedelic effects. METHOD(S): Male Sprague Dawley rats were trained in two lever operant conditioning chambers using the FR10 schedule of reinforcement to discriminate 0.08 mg/kg LSD from vehicle, 15 min following administration. The experiment was conducted 5 days/week during the light phase of the light/dark cycle. AIM(S): The aim was to examine the time after which the animals were able to discriminate two treatment conditions. Animals were tested 5, 15, 30, and 90 min after 0.08 mg/kg of LSD administration. RESULTS: All animals tested 15 min following LSD administration choose the LSD lever. In the test carried out after 5 min following injection, 70% of rats choose the LSD lever. The subjects tested after 30 min displayed similar discrimination as tested following 15 min. However, after 90 min following LSD administration, the rats choose the vehicle lever. CONCLUSIONS: The present data suggest that the cue produced by LSD in the drug discrimination test could be detected shortly after its administration.
6

SB 742,457, a 5-HT6 receptor antagonist, reverses cognitive impairment induced by scopolamine in the Novel Object Recognition Test in rats

51%
Kos T., Nikiforuk A., Zajdel P., Popik P.
Acta Neurobiologiae Experimentalis
|
2014
|
tom 74
|
nr 3
Serotonin (5-HT) type 6 antagonists have been regarded as cognition-enhancing principles associated with schizophrenia and Alzheimer’s disease. It has been proposed that these favorable effects are mediated through a blockade of excitatory tonic action of 5-HT6 receptors located at GABAergic neurons in the hippocampus and cortex. This blockade is leading to an indirect enhancement of cholinergic and glutamatergic neurotransmission. To evaluate the cognitive effects of SB 742,457, the novel object recognition test (NOR) was performed following scopolamineadministration. As a positive control, galantamine, a competitive and reversible cholinesterase inhibitor, was used. We report that compound SB 742,457 reversed scopolamine-induced memory impairment in a dose-dependent manner. The effect of higher dose of 1 mg/kg was as strong as an effect of a positive control, galantamine. Present data confirm that antagonists of 5-HT6 receptors exhibit pro-cognitive effects purportedly useful in the treatment of cognitive deficits associated with Alzheimer’s disease and schizophrenia. Supported by statutory funds from the Institute of Pharmacology, Polish Academy of Sciences (Cracow, Poland)
7

Positive allosteric modulation of nicotinic receptors: a new hope to treat cognitive deficits?

51%
Potasiewicz A., Nikiforuk A., Popik P.
Acta Neurobiologiae Experimentalis
|
2014
|
tom 74
|
nr 3
Alpha-7 nicotinic acetylcholine receptors (α7-nAChRs) represent the promising target for the development of new therapies of cognitive dysfunctions associated with schizophrenia and Alzheimer’s disease. Activation of these receptors produces procognitive effects. Recent data suggest that the positive allosteric modulators (PAMs) of α7-nAChRs may demonstrate a more favorable pharmacological profile than the orthosteric agonists. However, little is known about the potential efficacy of α7-nAChRs PAMs on cognitive processes. The aim of the present study was to evaluate the effects of the PNU 120596, an α7-nAChRs PAM (1 and 3 mg/kg, ip), on cognitive processes in rats. We used odor span test (OST), novel object recognition (NOR) task and 5-choice serial reaction time task (5-CSRTT) to assess the working memory capacity, episodic memory and attention, respectively. The compound enhanced episodic memory tested 24 h following its administration, however, PNU-120596 did not affect rat’s performance in OST and 5-CSRTT. The present study demonstrates the beneficial effects of PNU 120596 on some aspects of cognition in rats tested in cognition-unimpaired conditions. Further studies are now ongoing to evaluate the efficacy of this compound in cognition-deficit based models. Supported by the Polish National Science Centre grant NCN 2012/07/B/NZ/01150.
8

Rats that ‘gamble’ demonstrate impaired cognitive flexibility in the attentional set shifting task

51%
Rafa D., Potasiewicz A., Nikiforuk A., Popik P.
Acta Neurobiologiae Experimentalis
|
2014
|
tom 74
|
nr 3
Pathological gambling (PG), a behavioral addiction resembling substance abuse disorder can be modeled in laboratory rats using slot machine task (rSMT). Animals that respond to the cues suggesting, but not warranting food reward (‘near miss’ responses) can be classified as ‘gamblers’. This pathological response apparently persists in some animals and could be viewed as a behavioral trait. The correct response in this task involves a number of cognitive processes, including cognitive flexibility, i.e., an ability to adapt to the changing rules. This phenomenon may be assessed in rodents in the attentional set shifting task (ASST). We investigated whether ‘gamblers’ differed from ‘non-gamblers’ in cognitive flexibility. Animals were trained in rSMT by responding to a series of three flashing lights. A winning trial was signaled when all three lights were illuminated. At the end of each trial, rat chose between responding on the ‚collect‘ lever (that on the ‘win’ trials resulted in reward delivery, and on the ‘loose’ trials in a time penalty), or responding on the ‘roll’ lever that initiated the next trial. Then, the ‘gamblers’ and ‘non-gamblers’ were tested in the ASST. Animals exhibiting a ‘gambling’ trait required more trials to reach criterion at the Reversal and Extra Dimensional (ED) phases of ASST, that require animals to switch their attention to previously irrelevant stimulus exemplars or stimulus dimension, respectively. These results suggest that impairment of cognitive flexibility may play an important role in pathological gambling phenomenon. Supported by the grant NR 72/H/E/13 from the Ministry of Health
9

Pups' altered ultrasonic vocalisation in the poly I:C rat model of autism spectrum disorder: results from the mother isolation test

45%
Piotrowska D., Sopel J., Potasiewicz A., Popik P., Nikiforuk A.
Acta Neurobiologiae Experimentalis
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2019
|
tom 79
|
nr Suppl.1
INTRODUCTION: A large body of evidence suggests a connection between maternal infection during pregnancy and increased risk of developing autism spectrum disorder (ASD) in the child. One of the characteristic symptoms of ASD is deficits in communication. Rodent models of ASD include the administration of a synthetic double-stranded RNA, the polyinosinic-polycytidylic acid (poly(I:C)) to the pregnant dam, that evokes an antiviral‑like immune reaction. Rat pups isolated from their mother emit calls within ultrasonic spectrum of ~40 kHz. AIM(S): In this study, we examined whether poly I:C pups presented an altered pattern of ultrasonic vocalization (USV) during the mother isolation test. METHOD(S): Pregnant Sprague-Dawley dams received an intraperitoneal injection of poly I:C (5 mg/kg) or vehicle on GD 15. The isolation of male and female offspring was performed on PND 6. RESULTS: We observed changes in the number of vocalisations and an altered structure of emitted calls. Poly I:C males emitted less calls than control animals. A similar change in females was not observed. Both male and female poly I:C pups emitted calls of lower call bandwidth and peak frequency. CONCLUSIONS: Such changes of the structure of emitted calls suggest an impairment of vocal communication in the poly I:C animals. A decrease in the number of emitted calls in poly I:C males may reflect the fact that the prevalence and severity of symptoms of ASD is higher in boys and it appears that this higher susceptibility of males is present also in the poly I:C model. FINANCIAL SUPPORT: This study was supported by the Polish National Science Centre grant NCN 2016/23/B/NZ7/01131.
10

Social interactions and ultrasonic vocalisation in serotonin trasporter knockout rats

39%
Golebiowska J., Holuj M., Piotrowska D., Nikiforuk A., Popik P., Homberg J.
Acta Neurobiologiae Experimentalis
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2019
|
tom 79
|
nr Suppl.1
INTRODUCTION: The serotonergic system has been implicated in several CNS activities, including social behaviour. The serotonin reuptake transporter (SERT) plays a key role in the regulation of serotonergic system functioning. Therefore, rats lacking SERT (SERT- /- ) represent a valuable model to study the consequences of constitutive increases in serotonin concentrations. In adult laboratory rats, two main types of ultrasonic vocalisations (USVs) have been described: the low (22-kHz) and high (50‑kHz) frequency calls. The low, termed an “alarm” vocalization, has been associated with negative social experiences. The high may be detected in appetitive contexts, including social interactions. AIM(S): The goal of the current study was to examine male SERT- /- and SERT+ /+ rats in the social interaction test to investigate genotype differences in social behaviour and communication. METHOD(S): Two unfamiliar rats of matched body weight were placed in the open field arena, and their behaviour was recorded. Durations of the following behaviours were scored: social contact behaviour (including sniffing, anogenital sniffing, social grooming, and mounting/climbing) and following the partner. Additionally, USVs were measured during the social interaction tests. RESULTS: We report that SERT-/- rats spent significantly less time on social contact but demonstrated more of partner following behaviour as compared to SERT+ /+ rats. There were no effects of genotype on the number of 22-kHz and 50-kHz USVs emitted during social interaction. However, serotonin transporter deletion affected the distribution of sound categories in that SERT- /- rats demonstrated a decrease in the percentage of complex calls and an increase in the percentage of trill and step calls. CONCLUSIONS: The current study further supports the role of serotonin in the regulation of social and communicative behaviour. FINANCIAL SUPPORT: This study was supported by the grant ERA‑NET Neuron II JTC 2015 Respond.
11
Content available remote

Ghrelin - a new gastroprotective factor in gastric mucosa

33%
Konturek P. C., Brzozowski T., Pajdo R., Nikiforuk A., Kwiecien S., Harsch I., Drozdowicz D., Hahn E. G., Konturek S. J.
Journal of Physiology and Pharmacology
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2004
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tom 55
|
nr 2
Ghrelin, a novel peptide expressed in the gastrointestinal tract, especially in the gastric mucosa, exerts several biological activities including the stimulation of appetite and food intake, the stimulation of intestinal motility and the release of growth hormone. The aim of this study was to examine the expression of ghrelin in gastric mucosa after its exposure to ethanol and its effects on gastric lesions induced by ethanol with and without pretreatment with indomethacin. Acute gastric lesions were induced by intragastric administration of 75% ethanol in rats pretreated with saline-vehicle or ghrelin injected intraperitoneally (i.p.) without or with i.p. pretreatment with indomethacin. At the end of experiments, the rats were anesthetized, the stomach was exposed to measure gastric blood flow (GBF), to determine the area of gastric lesions and to take biopsy samples from the oxyntic mucosa for determination of transcripts of ghrelin, tumor necrosis alpha (TNF-alpha) and transforming growth factor alpha (TGFalpha) using RT-PCR and to assess the generation of PGE2 by RIA. Exposure of gastric mucosa to 75% ethanol resulted in numerous mucosal lesions of an area of about 115 mm2 and in the increase of mucosal expression of TNF-alpha, PGE2, TGFalpha and ghrelin with concomitant decrease in GBF. Exogenous ghrelin reduced dose-dependently acute gastric lesions with simultaneous attenuation of GBF and a decrease in the expression of TNF-alpha but not TGFalpha. Pretreatment with indometahcin, which suppressed the generation of PGE2 by about 85%, augmented ethanol-induced gastric lesions and eliminated the ghrelin-induced protection of mucosa against ethanol. We conclude that ghrelin, whose mucosal expression is enhanced after exposure to ethanol, exhibits a strong gastroprotection, at least in part, due to its anti-inflammatory action mediated by prostaglandins.
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