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1

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

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Holuj M., Nikiforuk A., Pupik P.
Acta Neurobiologiae Experimentalis
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2014
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tom 74
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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.
2

Social play behavior of rats in the model of autism induced by prenatal exposure to polyinosinic: polycytidylic acid

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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.
3

Activation of Alpha 7 nicotinic acetylcholine receptors against cognitive and sensorimotor gating deficits in animal model of schizophrenia

100%
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.
4

Social interactions and ultrasonic vocalisation in serotonin trasporter knockout rats

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Golebiowska J., Holuj M., Piotrowska D., Nikiforuk A., Popik P., Homberg J.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
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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.
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