Methadone is a Non-Competitive Antagonist at the α4β2 and α3* Nicotinic Acetylcholine Receptors and an Agonist at the α7 Nicotinic Acetylcholine Receptor

2014 ◽  
Vol 116 (4) ◽  
pp. 321-328 ◽  
Author(s):  
Reeta Talka ◽  
Outi Salminen ◽  
Raimo K. Tuominen
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Competitive Antagonist ◽  
Nicotinic Acetylcholine

scholarly journals Contrasting effects of the α7 nicotinic receptor antagonist methyllycaconitine in different rat models of heroin reinstatement

2021 ◽  
pp. 026988112199157
Author(s):  
Josephine Palandri ◽  
Sharon L Smith ◽  
David J Heal ◽  
Sue Wonnacott ◽  
Chris P Bailey
Keyword(s):  
Acetylcholine Receptor ◽  
Conditioned Place Preference ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Place Preference ◽  
Self Administration ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Α7 Nicotinic Acetylcholine Receptors

Background: α7 Nicotinic acetylcholine receptors are implicated in the reinstatement of drug-seeking, an important component of relapse. We showed previously that the α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, specifically attenuated morphine-primed reinstatement of conditioned place preference in rodents and this effect was mediated in the ventral hippocampus. Aims: The purpose of this study was to evaluate α7 nicotinic acetylcholine receptor antagonism in reinstatement of the conditioned place preference for the more widely abused opioid, heroin, and to compare the effect of α7 nicotinic acetylcholine receptor blockade on reinstatement of heroin-seeking and heroin self-administration in an intravenous self-administration model of addictive behaviour. Methods: Rats were trained to acquire heroin conditioned place preference or heroin self-administration; both followed by extinction of responding. Methyllycaconitine or saline was given prior to reinstatement of drug-primed conditioned place preference, or drug-prime plus cue-induced reinstatement of intravenous self-administration, using two protocols: without delivery of heroin in response to lever pressing to model heroin-seeking, or with heroin self-administration, using fixed and progressive ratio reward schedules, to model relapse. Results: Methyllycaconitine had no effect on acquisition of heroin conditioned place preference or lever-pressing for food rewards. Methyllycaconitine blocked reinstatement of heroin-primed conditioned place preference. Methyllycaconitine did not prevent drug-prime plus cue-induced reinstatement of heroin-seeking, reinstatement of heroin self-administration, or diminish the reinforcing effect of heroin. Conclusions: The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, prevented reinstatement of the opioid conditioned place preference, consistent with a role for α7 nicotinic acetylcholine receptors in the retrieval of associative memories of drug liking. The lack of effect of methyllycaconitine in heroin-dependent rats in two intravenous self-administration models suggests that α7 nicotinic acetylcholine receptors do not play a role in later stages of heroin abuse.

scholarly journals Toxic Effect of Cigarette Smoke on Brainstem Nicotinic Receptor Expression: Primary Cause of Sudden Unexplained Perinatal Death

Toxics ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 63 ◽  
Author(s):  
Anna Lavezzi
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Perinatal Death ◽  
Receptor Expression ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Vital Functions ◽  
Α7 Nicotinic Acetylcholine Receptors

Among the neurotoxicants contained in tobacco smoke, if absorbed during pregnancy, nicotine significantly affects α7-nicotinic acetylcholine receptors, which play essential roles in the development of the brainstem regions receiving cholinergic projections in perinatal life. Immunohistochemical procedures for analysing formalin-fixed and paraffin-embedded brainstem samples from 68 fetuses and early newborns, with smoking and non-smoking mothers, who died of known and unknown causes, were carried out in order to determine if nicotine had activated the α7-nicotinic acetylcholine receptors. High α7-nicotinic acetylcholine receptor expression levels were only observed in the victims with smoking mothers. Frequently, these findings were associated with the hypoplasia of the brainstem structures controlling vital functions. The results of this study indicate that the exposition to nicotine in pregnancy exerts a strong direct effect on α7-nicotinic acetylcholine receptor activity especially in perinatal life and may be one of the primary risk factors leading to the sudden unexplained death of fetuses and newborns.

Actions of the insecticide 2 (nitromethylene) tetrahydro-1, 3-thiazine on insect and vertebrate nicotinic acetylcholine receptors

1989 ◽  
Vol 237 (1289) ◽  
pp. 501-514 ◽  
Keyword(s):  
Rat Brain ◽  
Glutamate Receptors ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Reversal Potential ◽  
Muscarinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Agonist Action

The nitromethylene heterocyclic compound 2(nitromethylene)tetrahydro) 1, 3-thiazine (NMTHT) inhibits the binding of [ 125 I) α -bungarotoxin to membranes prepared from cockroach ( Periplaneta americana ) nerve cord and fish ( Torpedo californica ) electric organ. Electrophysiological studies on the cockroach fast coxal depressor motorneuron (D f ) reveal a dose-dependent depolarization in response to bath-applied NMTHT. Responses to ionophoretic application of NMTHT on to the cell-body membrane of motorneuron D f are suppressed by bath-applied mecamylamine (1.0 x 10 -4 M) and α -bungarotoxin (1.0 x 10 -7 M). These findings, together with the detection of a reversal potential close to that estimated for acetylcholine, provide evidence for an agonist action of this nitromethylene on an insect neuronal nicotinic acetylcholine receptor. The binding of [ 3 H]H 12 -histrionicotoxin to Torpedo membranes was enhanced in the presence of NMTHT indicating an agonist action at this vertebrate peripheral nicotinic acetylcholine receptor. NMTHT is ineffective in radioligand binding assays for rat brain GABA A receptors, rat brain L-glutamate receptors and insect ( Musca domestica ) L-glutamate receptors. Partial block of rat brain muscarinic acetylcholine receptors is detected at millimolar concentrations of NMTHT. Thus nitromethylenes appear to exhibit selectivity for acetylcholine receptors and exhibitan agonist action at nicotinic acetylcholine receptors.

scholarly journals Effects of Bis(7)-Tacrine on Spontaneous Synaptic Activity and on the Nicotinic ACh Receptor of Torpedo Electric Organ

2001 ◽  
Vol 86 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Esteve Ros ◽  
Jordi Aleu ◽  
Inmaculada Gomez De Aranda ◽  
Carles Cantí ◽  
Yuan-Ping Pang ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Electric Organ ◽  
Synaptic Activity ◽  
Hill Coefficient ◽  
Nicotinic Acetylcholine ◽  
Torpedo Electric Organ ◽  
Induced Currents

Bis(7)-tacrine is a potent acetylcholinesterase inhibitor in which two tacrine molecules are linked by a heptylene chain. We tested the effects of bis(7)-tacrine on the spontaneous synaptic activity. Miniature endplate potentials (MEPPs) were recorded extracellularly on slices of electric organ of Torpedo marmorata. Bis(7)-tacrine, at a concentration of 100 nM, increased the magnitudes that describe MEPPs: amplitude, area, rise time, rate of rise, and half-width. We also tested the effect of bis(7)-tacrine on nicotinic acetylcholine receptors by analyzing the currents elicited by acetylcholine (100 μM) in Torpedo electric organ membranes transplanted in Xenopus laevis oocytes. Bis(7)-tacrine inhibited the acetylcholine-induced currents in a reversible manner (IC50 = 162 nM). The inhibition of nicotinic acetylcholine receptors was not voltage dependent, and bis(7)-tacrine increased the desensitization of nicotinic acetylcholine receptors. The Hill coefficient for bis(7)-tacrine was −0.72 ± 0.02, indicating that bis(7)-tacrine binds to the nicotinic acetylcholine receptor in a molecular ratio of 1:1, but does not affect the binding of α-bungarotoxin with the nicotinic acetylcholine receptor. In conclusion, bis(7)-tacrine greatly increases the spontaneous quantal release from peripheral cholinergic terminals at a much lower concentration than tacrine. Bis(7)-tacrine also blocks acetylcholine-induced currents of Torpedo electric organ, although the mechanism is different from that of tacrine: bis(7)-tacrine enhances desensitization, whereas tacrine reduces it.

scholarly journals Procognitive effects of varenicline in the animal model of schizophrenia depend on α4β2- and α7-nicotinic acetylcholine receptors

2018 ◽  
Vol 33 (1) ◽  
pp. 62-73 ◽  
Author(s):  
Agnieszka Potasiewicz ◽  
Joanna Golebiowska ◽  
Piotr Popik ◽  
Agnieszka Nikiforuk
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Partial Agonist ◽  
Set Shifting ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
Α7 Nachrs

Background: Varenicline, a partial agonist of the α4β2 nicotinic acetylcholine receptor (α4β2-nAChR), is currently used to facilitate smoking cessation. Preclinical and clinical studies have suggested that this compound may also be effective in treating cognitive impairments in schizophrenia. However, it is unclear which nicotinic acetylcholine receptor subtypes may be involved because varenicline is not only a partial agonist for α4β2-nAChRs but also a full agonist for α7 nicotinic acetylcholine receptors (α7-nAChRs). Aim: We investigated the effects of varenicline, compared to the α4β2-nAChR partial agonist TC-2403 and the α7-nAChR full agonist PNU-282987, in a ketamine-based model of schizophrenia-like cognitive deficits on the attentional set-shifting task in rats. The second goal was to elucidate whether the procognitive efficacy of varenicline was due to the compound’s action on α4β2-nAChRs or α7-nAChRs. Methods: Ketamine was administered to rats for 10 consecutive days and the test was performed 14 days following the last injection. The tested compounds were administered 30 min prior to the attentional set-shifting task. Results: Varenicline, TC-2403 and PNU-282987 ameliorated ketamine-evoked set-shifting deficits. While the α4β2-nAChR antagonist dihydro-β-erythroidine and the α7-nAChR antagonist methyllycaconitine completely prevented the procognitive actions of TC-2403 and PNU-282987, respectively, varenicline’s effect was only partially blocked by any given antagonist. Moreover, the combined treatment with TC-2403 and PNU-282987 more effectively facilitated rats’ set-shifting ability than activation of either type of nicotinic acetylcholine receptor alone. Conclusion: The present findings demonstrated that varenicline’s actions on both α7-nAChRs and α4β2-nAChRs may be necessary to produce its full procognitive effect in the present experimental setting.

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