AIMS: Although a pharmacological relationship is known to exist between nicotine and morphine, the exact mechanisms are unclear. Here, we investigated crosstalk between the endogenous opioid system and nicotinic acetylcholine receptors (nAChRs), specifically in nicotine-induced analgesia and activation of the hypothalamic-pituitary-adrenal (HPA) axis. MAIN METHODS: Nicotine and morphine were administered subcutaneously to mice and the effects of these drugs on analgesia and serum corticosterone (SCS) levels were evaluated by the tail-pinch method and fluorometric assay, respectively. KEY FINDINGS: Both nicotine and morphine produced analgesia and SCS increase after a single injection. Nicotine-induced analgesia was prevented by both mecamylamine (MEC; 1mg/kg) and naloxone (NLX; 1mg/kg), and also by repeated administration of morphine or nicotine. Morphine-induced analgesia was prevented by NLX, but not MEC, and by repeated administration of morphine, but not nicotine. Conversely, the nicotine-induced increase in SCS level was prevented by MEC, but not NLX. Morphine-induced SCS increase was prevented by NLX, but not MEC. Moreover, nicotine-induced analgesia was suppressed by dihydro-β-erythroidine (DHβE; an antagonist for the α4β2 nAChR) or methyllycaconitine (MLA; an antagonist for the α7 nAChR). The nicotine-induced increase in SCS level was suppressed by DHβE, but not MLA. SIGNIFICANCE: Nicotine-induced analgesia may involve the endogenous opioid system through crosstalk with nicotinic pathways. However, the relationship between these systems does not extend to cooperative actions in nicotine-induced HPA-axis activation.
AIMS: Although a pharmacological relationship is known to exist between nicotine and morphine, the exact mechanisms are unclear. Here, we investigated crosstalk between the endogenous opioid system and nicotinic acetylcholine receptors (nAChRs), specifically in nicotine-induced analgesia and activation of the hypothalamic-pituitary-adrenal (HPA) axis. MAIN METHODS:Nicotine and morphine were administered subcutaneously to mice and the effects of these drugs on analgesia and serum corticosterone (SCS) levels were evaluated by the tail-pinch method and fluorometric assay, respectively. KEY FINDINGS: Both nicotine and morphine produced analgesia and SCS increase after a single injection. Nicotine-induced analgesia was prevented by both mecamylamine (MEC; 1mg/kg) and naloxone (NLX; 1mg/kg), and also by repeated administration of morphine or nicotine. Morphine-induced analgesia was prevented by NLX, but not MEC, and by repeated administration of morphine, but not nicotine. Conversely, the nicotine-induced increase in SCS level was prevented by MEC, but not NLX. Morphine-induced SCS increase was prevented by NLX, but not MEC. Moreover, nicotine-induced analgesia was suppressed by dihydro-β-erythroidine (DHβE; an antagonist for the α4β2 nAChR) or methyllycaconitine (MLA; an antagonist for the α7 nAChR). The nicotine-induced increase in SCS level was suppressed by DHβE, but not MLA. SIGNIFICANCE: Nicotine-induced analgesia may involve the endogenous opioid system through crosstalk with nicotinic pathways. However, the relationship between these systems does not extend to cooperative actions in nicotine-induced HPA-axis activation.
Authors: Ana F Castillo; Ulises D Orlando; Paula M Maloberti; Jesica G Prada; Melina A Dattilo; Angela R Solano; María M Bigi; Mayra A Ríos Medrano; María T Torres; Sebastián Indo; Graciela Caroca; Hector R Contreras; Belkis E Marelli; Facundo J Salinas; Natalia R Salvetti; Hugo H Ortega; Pablo Lorenzano Menna; Sergio Szajnman; Daniel E Gomez; Juan B Rodríguez; Ernesto J Podesta Journal: Cell Mol Life Sci Date: 2020-10-17 Impact factor: 9.261
Authors: Amanda K Fakira; Emily G Peck; Yutong Liu; Lindsay M Lueptow; Nikita A Trimbake; Ming-Hu Han; Erin S Calipari; Lakshmi A Devi Journal: Neuropharmacology Date: 2019-06-12 Impact factor: 5.250
Authors: Fair M Vassoler; Michelle L Oranges; Anika M Toorie; Elizabeth M Byrnes Journal: Pharmacol Biochem Behav Date: 2018-07-26 Impact factor: 3.533