Differential effects of α7 nicotinic receptor agonist PHA-543613 on spatial memory performance of rats in two distinct pharmacological dementia models

Bali, Zsolt Kristóf; Inkeller, Judit; Csurgyók, Roland; Bruszt, Nóra; Horváth, Hajnalka; Hernádi, István

doi:10.1016/j.bbr.2014.10.030

Cited by 19 publications

(21 citation statements)

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“…A previous study found that ziprasidone might improve performance in MWM in MK-801-treated mice, whereas there was no effect in naïve mice (Tanyeri et al, 2015). PHA-543613 is a highly selective alpha-7 nicotinic acetylcholine receptor agonist with cognitive enhancer potential, but produced little efficacy in terms of the memory deficit of MK-801-treated rats in the previous study (Bali et al, 2015).…”

Section: Introductionmentioning

confidence: 89%

Effects of haloperidol, olanzapine, ziprasidone, and PHA‐543613 on spatial learning and memory in the Morris water maze test in naïve and MK‐801‐treated mice

et al. 2017

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Introduction Cognitive impairment is the core symptom of schizophrenia, significantly impacting the functional outcome. Improvement of cognitive function has been an important aspect of the treatment of schizophrenia. Therefore, this study is to demonstrate the effects of first‐generation antipsychotic haloperidol, second‐generation antipsychotic olanzapine and ziprasidone, and alpha‐7 nicotinic acetylcholine receptor agonist PHA ‐543613 on spatial learning and memory. Material and Methods C57 BL /6 mice received intraperitoneal injections of haloperidol (2 mg/kg), olanzapine (2.5 mg/kg), ziprasidone (2 mg/kg), and PHA ‐543613 (1 mg/kg), and cognitive dysfunctions were induced by MK ‐801 (0.1 mg/kg). Morris water maze was used for investigating the effects of all agents. Results Mk‐801 significantly increased the mean escape latency to the platform and decreased the number of platform area crossings. Ziprasidone had no effect on the mean escape latency to platform and the number of platform area crossings in naïve mice, but haloperidol, olanzapine, and PHA ‐543613 did not. Haloperidol and olanzapine significantly increased the mean escape latency to platform and decreased the number of platform area crossings, while ziprasidone and PHA ‐543613 did not. All the agents had no effect on swimming speed. Conclusions Ziprasidone and alpha‐7 nicotinic acetylcholine receptor agonist PHA ‐543613 might be helpful in the treatment of CIAS .

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Section: Introductionmentioning

confidence: 89%

Effects of haloperidol, olanzapine, ziprasidone, and PHA‐543613 on spatial learning and memory in the Morris water maze test in naïve and MK‐801‐treated mice

et al. 2017

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“…There is a large body of evidence for the cognitive enhancing effects of both alpha7 nAChR agonists and PAMs (for review, see Pandya and Yakel (2013), and Wallace and Porter (2011)). Specifically, PHA-543613, NS-1738 and PNU-120596 were also found effective in improving cognitive performance in different behavioral paradigms in different animal models (Timmermann et al, 2007;Bali et al, 2015;Nikiforuk et al, 2015;Sadigh-Eteghad et al, 2015;. At the moment, it is still not possible to decide whether the desensitization of alpha7 nAChRs decreases the efficacy of agonist compounds in cognitive enhancement.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of alpha7 nAChRs by agonists or PAMs has already been shown to be effective to enhance learning and memory in several behavioral tests in preclinical animal models of various cognitive disorders (Ng et al, 2007;Timmermann et al, 2007;Bali et al, 2015;Nikiforuk et al, 2015; for a review see Wallace and Porter, 2011). Moreover, both alpha7 nAChR agonists and PAMs have been reported to show interaction with the effects of memantine in behavioral experiments Bali et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Facilitation and inhibition of firing activity and N-methyl-D-aspartate-evoked responses of CA1 hippocampal pyramidal cells by alpha7 nicotinic acetylcholine receptor selective compounds in vivo

Bali

Nagy

Budai³

et al. 2019

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Alpha7 nicotinic acetylcholine receptors (nAChRs) are promising novel targets for the treatment of neurocognitive disorders. Although the cognitive enhancer potential of alpha7 nAChR agonists and positive allosteric modulators (PAMs) has been confirmed in several preclinical animal models, there are only sparse in vivo electrophysiological data on their effects on the firing activity and excitability of neurons. The present study investigated and compared local effects of alpha7 nAChR agonist PHA-543613 and PAMs PNU-120596 and NS-1738 on the spontaneous and N-methyl-D-aspartate-evoked (NMDA-evoked) firing rate of rat CA1 hippocampal pyramidal cells, in vivo. Furthermore, effects of alpha7 nAChR antagonist methyllycaconitine (MLA) and GABA were also tested. Results showed substantially different effects of the alpha7 nAChR agonist and PAMs. While PNU-120596 and NS-1738 predominantly and significantly increased both spontaneous and NMDA-evoked firing rate of the neurons, application of PHA-543613 resulted in almost equal distribution of facilitatory and inhibitory effects. The increase of the NMDA-evoked firing rate exerted by NS-1738 was superadditive over the sum of the single effects of NMDA and NS-1738. The simultaneous application of alpha7 nAChR agonist PHA-543613 and PAM NS-1738 resulted in additive increase of both spontaneous and NMDA-evoked firing rate. However, NS-1738 counteracted inhibitory effects of PHA-543613 in 5 out of 6 neurons, resulting in a synergistic potentiation of their firing responses to NMDA. Our results suggest that alpha7 nAChRPAMs increase neuronal excitability more potently than agonists, while the remarkable occurrence of inhibitory effects of PHA-543613 (possibly originating from receptor desensitization) implies that agonists may exert neuroprotective effects.

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“…Our recently-published paper showed its ameliorative effects on spatial memory in Aβ-treated animals 15 . Bali et al described PHA-543613's procognitive effects on T-maze in the scopolamineinduced memory impairment model 7 . Activation of α7-nAChR by various agonists showed improvement in recognition memory in different studies.…”

Section: Effect Of Alpha-7 Nicotinic Acetylcholine Receptor Activatiomentioning

confidence: 99%

“…Moreover, α7-nAChR activation decreases Aβ-induced neurotoxicity 6 . Studies have shown that α7-nAChR activation may represent a therapeutic strategy for AD-related cognitive impairments 7 . Also, the cholinergic-vascular hypothesis, suggests that the loss of cholinergic vascular innervation is responsible for the impairment of cerebral blood flow (CBF) in AD 8 .…”

Section: Introductionmentioning

confidence: 99%

Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

et al. 2015

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PURPOSE:To evaluate the effects of PHA-543613 (α7-nAChR agonist) and galantamine (acetylcholinesterase inhibitor (AChEI)) on recognition memory and neurovascular coupling (NVC) response in beta-amyloid (Aβ) 25-35 -treated mice. METHODS:PHA-543613 (1 mg/kg, i.p.), and galantamine (3 mg/kg, s.c.), effects were tested in Aβ 25-35 mice model of AD. α7-nAChR antagonist, methyllycaconitine (MLA) (1 mg/kg, i.p.), was used for evaluation of receptor blockade effects. Recognition memory in animals was assessed by the novel object recognition (NOR) task. NVC response was analyzed by laser-doppler flow meter in barrel cortex by whisker stimulation method. RESULTS:Both, PHA-543613 and galantamine improve recognition memory in Aβ-treated animals. However, the advantageous effects of PHA-543613 were significantly higher than galantamine. Also, pretreatment with MLA reversed both galantamine and PHA-543613 effects on NOR. Impaired NVC response in AD animals was improved by PHA-543613 and galantamine. However, MLA pretreatment disrupts this function. CONCLUSION: Activation of α7-nAChR improved recognition memory possible through enhancement of neurovascular response inAlzheimer's disease in animals.Key words: Amyloid beta-Peptides. Recognition. Receptors, Nicotinic. Mice. Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

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Differential effects of α7 nicotinic receptor agonist PHA-543613 on spatial memory performance of rats in two distinct pharmacological dementia models

Cited by 19 publications

References 58 publications

Effects of haloperidol, olanzapine, ziprasidone, and PHA‐543613 on spatial learning and memory in the Morris water maze test in naïve and MK‐801‐treated mice

Effects of haloperidol, olanzapine, ziprasidone, and PHA‐543613 on spatial learning and memory in the Morris water maze test in naïve and MK‐801‐treated mice

Facilitation and inhibition of firing activity and N-methyl-D-aspartate-evoked responses of CA1 hippocampal pyramidal cells by alpha7 nicotinic acetylcholine receptor selective compounds in vivo

Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

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