Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms

Hamouda, Ayman K.; Bautista, Malia; Akinola, Lois S.; Alkhlaif, Yasmin; Jackson, Asti; Carper, Moriah; Toma, Wisam; Garai, Sumanta; Chen, Yen-Chu; Thakur, Ganesh A.; Fowler, Christie D.; Damaj, M. Imad

doi:10.1016/j.neuropharm.2021.108568

Cited by 9 publications

(3 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In each case, receptor upregulation induced by individual agents correlated with their in vitro potency for inhibiting [ 3 H] nicotine binding (Tomizawa & Casida, 2000 ). The upregulation of a high nicotine sensitivity α4β2 (α4(x2) β2(x3)) receptors is thought to drive preference seeking behaviour in humans (Ngolab et al, 2015 ) and nicotine alone has reinforcing actions (Hamouda et al, 2021 ). Similarly, preference seeking behaviour have also been reported in honeybees (Kessler et al, 2015 ) and the bumblebee B. terrestris (Arce et al, 2018 ; Kessler et al, 2015 ), but not B. impatiens (Muth et al, 2020 ) with field‐relevant levels of the neonicotinoids, thiamethoxam or imidacloprid.…”

Section: Chronic Exposure To Pesticides May Alter the Pharmacological...mentioning

confidence: 99%

Environmental pharmacology—Dosing the environment: IUPHAR review 36

Connolly¹,

Alexander

Davies

et al. 2022

British J Pharmacology

View full text Add to dashboard Cite

Pesticide action is predominantly measured as a toxicological outcome, with pharmacological impact of sublethal doses on bystander species left largely undocumented. Likewise, chronic exposure, which often results in responses different from acute administration, has also been understudied. In this article, we propose the application of standard pharmacological principles, already used to establish safe clinical dosing regimens in humans, to the ‘dosing of the environment’. These principles include relating the steady state dose of an agent to its beneficial effects (e.g. pest control), while minimising harmful impacts (e.g. off‐target bioactivity in beneficial insects). We propose the term ‘environmental therapeutic window’, analogous to that used in mammalian pharmacology, to guide risk assessment. To make pharmacological terms practically useful to environmental protection, quantitative data on pesticide action need to be made available in a freely accessible database, which should include toxicological and pharmacological impacts on both target and off‐target species.

show abstract

Section: Chronic Exposure To Pesticides May Alter the Pharmacological...mentioning

confidence: 99%

Environmental pharmacology—Dosing the environment: IUPHAR review 36

Connolly¹,

Alexander

Davies

et al. 2022

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Subunit diversity yields different nAChR subtypes, each having unique biophysical properties, including permeability to calcium and ligand sensitivity (Hernández-Vivanco et al, 2014; Jones et al, 1999; Papke, 1993). Studies show that the most prevalent nAChR subtypes in the CNS contain β2 and α4 subunits, which can heterodimerize to form various subtypes, including α4β2, α4α6β2, and α4(2)α5β2(2) nAChRs (*denotes that these nAChRs can contain other α and β subunits) (Flores et al, 1992; Gotti et al, 2009; Hamouda et al, 2021; Liu et al, 2003; Moroni et al, 2006). α4β2* nAChRs have been implicated in a variety of diseases as possible targets for the treatment of nicotine dependence, pain, as well as many cognitive and neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and Tourette’s syndrome (McEvoy and Allen, 2002; Okada et al, 2013; Quik and Wonnacott, 2011); however, the heterogeneity displayed by this receptor system has made it challenging to investigate specific subunits in isolation, and finding selective tools to investigate these subtypes has proved difficult (Alkondon and Albuquerque, 2004; Fowler et al, 2008; Improgo et al, 2010; Levin, 2002; Pimlott et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background: Because of their implications in several pathological conditions, α4β2* nicotinic acetylcholine receptors (nAChRs) are potential targets for the treatment of nicotine dependence, pain, and many psychiatric and neurodegenerative diseases. However, they exist in various subtypes, and finding selective tools to investigate them has proved challenging. The nicotinic receptor agonist, 5-iodo-A-85380 (5IA), has helped in delineating the function of β2-containing subtypes in vitro; however, much is still unknown about its behavioral effects. Furthermore, its effectiveness on α6-containing subtypes is limited. Aims: To investigate the effects of 5IA on nociception (formalin, hot-plate, and tail-flick tests), locomotion, hypothermia, and conditioned reward after acute and repeated administration, and to examine the potential role of β2 and α6 nAChR subunits in these effects. Lastly, its selectivity for expressed low sensitivity (LS) and high sensitivity (HS) α4β2 receptors is investigated. Results: 5IA dose-dependently induced hypothermia, locomotion suppression, conditioned place preference, and antinociception (only in the formalin test but not in the hot-plate or tail-flick tests). Furthermore, these effects were mediated by β2 but not α6 nicotinic subunits. Finally, we show that 5-iodo-A-85380 potently activates both stoichiometries of α4β2 nAChRs with differential efficacies, being a full agonist on HS α4(2)β2(3) nAChRs, and a partial agonist on LS α4(3)β2(2) nAChRs and α6-containing subtypes as well.

show abstract

“…Assembly of both α4β2 nAChR isoforms has been reported in vivo ( 16 ). The (α4)3(β2)2 nAChR isoform is considered the major isoform expressed in the cortex ( 17 ), whereas the (α4)2(β2)3 nAChR isoform contributes to nicotine dependence and is selectively upregulated and stabilized after chronic nicotine exposure ( 18 , 19 , 20 , 21 ).…”

mentioning

confidence: 99%

Assessing potentiation of the (α4)3(β2)2 nicotinic acetylcholine receptor by the allosteric agonist CMPI

Deba

Munoz

Peredia

et al. 2022

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms

Cited by 9 publications

References 73 publications

Environmental pharmacology—Dosing the environment: IUPHAR review 36

Environmental pharmacology—Dosing the environment: IUPHAR review 36

Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice

Assessing potentiation of the (α4)3(β2)2 nicotinic acetylcholine receptor by the allosteric agonist CMPI

Contact Info

Product

Resources

About