Selective nicotinic receptor antagonists: effects on attention and nicotine-induced attentional enhancement

Hahn, Britta; Shoaib, Mohammed; Stolerman, I. P.

doi:10.1007/s00213-011-2258-8

Cited by 48 publications

(33 citation statements)

References 49 publications

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“…On the same task, the α7 nicotinic antagonist MLA also showed efficacy in reversing dizocilpine-induced attentional impairment. This finding is in line with previous research into the effect of low dose MLA on attentional enhancement (Hahn et al, 2011). …”

Section: Introductionsupporting

confidence: 93%

Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats

Burke

Heshmati

Kholdebarin

et al. 2014

European Journal of Pharmacology

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Nicotinic systems have been shown by a variety of studies to be involved in cognitive function. Nicotinic receptors have an inherent property to become desensitized after activation. The relative role of nicotinic receptor activation vs. net receptor inactivation by desensitization in the cognitive effects of nicotinic drugs remains to be fully understood. In these studies, we tested the effects of the α7 nicotinic receptor antagonist methyllycaconitine (MLA), the α4β2 nicotinic receptor antagonist dihydro-β-erythroidine (DHβE), the nonspecific nicotinic channel blocker mecamylamine and the α4β2 nicotinic receptor desensitizing agent sazetidine-A on learning in a repeated acquisition test. Adult female Sprague-Dawley rats were trained on a repeated acquisition learning procedure in an 8-arm radial maze. MLA (1–4 mg/kg), DHβE (1–4 mg/kg), mecamylamine (0.125–0.5 mg/kg) or sazetidine-A (1 and 3 mg/kg) were administered in four different studies either alone or together with the NMDA glutamate antagonist dizocilpine (0.05 and 0.10 mg/kg). MLA significantly counteracted the learning impairment caused by dizocilpine. The overall choice accuracy impairment caused by dizocilpine was significantly attenuated by co-administration of DHβE. Low doses of the non-specific nicotinic antagonist mecamylamine also reduced dizocilpine-induced repeated acquisition impairment. Sazetidine-A reversed the accuracy impairment caused by dizocilpine. These studies provide evidence that a net decrease in nicotinic receptor activity can improve learning by attenuating learning impairment induced by NMDA glutamate blockade. This adds to evidence in cognitive tests that nicotinic antagonists can improve cognitive function. Further research characterizing the efficacy and mechanisms underlying nicotinic antagonist and desensitization induced cognitive improvement is warranted.

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Section: Introductionsupporting

confidence: 93%

Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats

Burke

Heshmati

Kholdebarin

et al. 2014

European Journal of Pharmacology

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“…Administration of α7 nAChR full/partial agonists or positive allosteric modulators (PAMs) exerted beneficial effects on attention, working and recognition memory, and cognitive flexibility in normal rodents and aged non-human primates (Boess et al, 2007; Bitner et al, 2007; Callahan et al, 2013; Levin et al, 1999; Nikiforuk et al, 2016; Rezvani et al, 2009; Tietje et al, 2008). On the other hand, systemic or intracranial infusions of α7 nAChR antagonist produced impairments in attention and working memory in normal rats (Chan et al, 2007; Hahn et al, 2011; Levin et al, 2002). α7 nAChR modulators have also been shown to improve attention and cognitive flexibility in animal models used to study cognitive symptoms of schizophrenia such as the developmental models (neonatal rat ventral hippocampus lesion, th(tk-)/th(tk-) mice), models of NMDA glutamate receptor hypofunction (MK801, phencyclidine, ketamine, kynurenic acid) and inbred mouse model (DBA/2J) with poor sensory gating (Alexander et al, 2012; Barak et al, 2009; Brooks et al, 2012; Hauser et al, 2009; Jones et al, 2014; McLean et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives

Parikh

Kutlu

Gould

2016

Schizophrenia Research

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Introduction The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. Methods Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 275 articles were used for the qualitative synthesis of this review. Results Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. Conclusions The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence.

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“…Methyllycaconitine (MLA) is a selective a7 nAChR competitive antagonist, and dihydro-beta-erythroidine (DHbE) is a selective a4b2 nAChR competitive antagonist. Both of these drugs have been shown to induce memory deficits in rodents [32], when administered at a high enough dose [33]. Besides inducing cognitive deficits on their own, these drugs are also used to counteract the procognitive effect of agonists at their corresponding nAChR subtype.…”

Section: Inhibition Of Energy/glucose Metabolismmentioning

confidence: 99%

“…Besides inducing cognitive deficits on their own, these drugs are also used to counteract the procognitive effect of agonists at their corresponding nAChR subtype. This approach is used in order to confirm that the procognitive effects of a selective nAChR agonist are indeed mediated via a specific nAChR [27,33].…”

Section: Inhibition Of Energy/glucose Metabolismmentioning

confidence: 99%

Cognitive Disorders: Impairment, Aging, and Dementia

Goethem

Lardenoije

Kompotis

et al. 2014

In Vivo Models for Drug Discovery

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Selective nicotinic receptor antagonists: effects on attention and nicotine-induced attentional enhancement

Cited by 48 publications

References 49 publications

Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats

Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives

Cognitive Disorders: Impairment, Aging, and Dementia

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