Behavioral effects of PNU-282987, an alpha7 nicotinic receptor agonist, in mice

Vicens, Paloma; Ribes, Diana; Torrente, Margarita; Domingo, José L.

doi:10.1016/j.bbr.2010.08.015

Cited by 39 publications

(38 citation statements)

References 47 publications

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“…Finally, a subset of a6-containing nAChRs (a6b2b3*) regulates sustained release on dopamine nerve terminals and, therefore, may provide the efficacy through which both short-term and long-term ABT-089 alleviate withdrawal symptoms (Marks et al, 2009). To date, a7 nAChRs have not been implicated in anxiety during nicotine withdrawal (Vicens et al, 2011), and they do not appear to be necessary for somatic signs of withdrawal (Markou and Paterson, 2001). However, as short-term ABT-107 reduced latency to consume during nicotine withdrawal, the targeting of a7 nAChRs may relieve withdrawal symptoms by activating nAChRs in the absence of nicotine.…”

Section: Anxiolytic Effects and Nachr Regulation Of Abt-089 Discussionmentioning

confidence: 99%

“…For example, alterations in the activation of the a4 nAChR subunit result in heightened anxiety (Ross et al, 2000;Labarca et al, 2001). Furthermore, although a7 nAChRs have not been implicated directly in anxiety (Paylor et al, 1998;Vicens et al, 2011) they are necessary in the ventral tegmental area for the expression of withdrawal from nicotine, suggesting that targeting of the a7 subtype may also relieve nicotine withdrawal symptoms (Nomikos et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Activation ofα4β2/α6β2 Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

Yohn

Turner

Blendy

2014

J Pharmacol Exp Ther

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Although nicotine mediates its effects through several nicotinic acetylcholine receptor (nAChR) subtypes, it remains to be determined which nAChR subtypes directly mediate heightened anxiety during withdrawal. Relative success in abstinence has been found with the nAChR partial agonist varenicline (Chantix; Pfizer, Groton, CT ); however, treatment with this drug fails to alleviate anxiety in individuals during nicotine withdrawal. Therefore, it is hypothesized that success can be found by the repurposing of other nAChR partial agonists for cessation therapies that target anxiety. It is noteworthy that the selective partial agonists for a4b2, ABT-089 [2-methyl-3-[2(S)-pyrrolidinylmethoxy]pyridine], and a7, ABT-107North Chicago, IL), have not been evaluated as possible therapeutics for nicotine cessation. Therefore, we examined the effect of ABT-089 and ABT-107 on anxiety during withdrawal from nicotine in the novelty-induced hypophagia (NIH) paradigm. We found that short-term administration of ABT-089 and ABT-107 alleviate anxiety-like behavior during withdrawal from nicotine while long-term administration of ABT-089 but not ABT-107 reduces anxiety-like behavior during withdrawal. After behavioral testing, brains were harvested and b2-containing nAChRs were measured using [3 H]epibaditine. ABT-089 and ABT-107 do not upregulate nAChRs, which is in contrast to the upregulation of nAChRs observed after nicotine. Furthermore, ABT-089 is anxiogenic in nicotine naive animals, suggesting that the effects on anxiety are specifically related to the nicotinedependent state. Together, these studies identify additional nAChR partial agonists that may aid in the rational development of smoking cessation aids.

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Section: Anxiolytic Effects and Nachr Regulation Of Abt-089 Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation ofα4β2/α6β2 Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

Yohn

Turner

Blendy

2014

J Pharmacol Exp Ther

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“…PNU-282987 showed both selectivity and potency as an a7 nAChR agonist (K i = 29 nM), retaining full agonist efficacy relative to nicotine in functional assays . PNU-282987 has been thoroughly characterized both in vitro and in vivo, demonstrating the restoration of P50 gating deficits in rodents, and has served as a tool molecule to advance basic research efforts Vicens et al, 2010;McLean et al, 2011). However, a major drawback of this compound was the interaction with the human ether à go-go-related gene (hERG) channel, which could represent a major cardiovascular risk (Walker et al, 2006).…”

Section: Gts-21mentioning

confidence: 99%

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

et al. 2015

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“…In addition, NO has neuroprotective effects by acting as a potent antioxidant or an inhibitor of apoptosis-related enzymes [27,28] , and then could modulate the function and expression of α7 nAChR directly or indirectly. As noted, α7 nAChRs are thought to improve spatial learning and memory and neuronal plasticity [6,29,30] . Therefore, it is possible that some of the effects of NO on learning and memory are mediated through an increase of α7 nAChR expression.…”

Section: Discussionmentioning

confidence: 92%

Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

et al. 2013

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Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of L-arginine and N ω -nitro-Larginine methylester (L-NAME, a nitric oxide synthase inhibitor) on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor), L-NAME, or 0.9% NaCl (control), once daily for seven consecutive days. Twelve hours after the last injection, they underwent an electric shock-paired Y maze test. Twenty-four hours later, the rats' memory of the safe illuminated arm was tested. After that, the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memory-testing session. In contrast, L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memory-testing session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. Similarly, α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Y-maze.

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Behavioral effects of PNU-282987, an alpha7 nicotinic receptor agonist, in mice

Cited by 39 publications

References 47 publications

Activation ofα4β2/α6β2 Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

Activation ofα4β2/α6β2 Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

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Behavioral effects of PNU-282987, an alpha7 nicotinic receptor agonist, in mice

Cited by 39 publications

References 47 publications

Activation ofα4β2*/α6β2* Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

Activation ofα4β2*/α6β2* Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

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Product

Resources

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Activation ofα4β2/α6β2 Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors

Activation ofα4β2/α6β2 Nicotinic Receptors Alleviates Anxiety during Nicotine Withdrawal Without Upregulating Nicotinic Receptors