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

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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.

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

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Potasiewicz A., Nikiforuk A., Popik P.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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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.

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

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Rafa D., Potasiewicz A., Nikiforuk A., Popik P.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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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

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

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Piotrowska D., Sopel J., Potasiewicz A., 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: 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.

Ograniczanie wyników

4 Acta Neurobiologiae Experimentalis

4 Nikiforuk A.

4 Popik P.

4 Potasiewicz A.

1 Holuj M.

1 Piotrowska D.

1 Rafa D.

1 Sopel J.

1 2019

1 2015

2 2014

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

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

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

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