title: Possible involvement of endogenous opioid system located downstream of α7 nicotinic acetylcholine receptor in mice with physical dependence on nicotine.
abstract: We previously reported that nicotine (NIC)-induced analgesia was elicited in part by activation of the endogenous opioid system. Moreover, it is well known that NIC has physical-dependence liability, but its mechanism is unclear. Therefore, we examined whether physical dependence on NIC was mediated by activation of the endogenous opioid system in ICR mice. We evaluated increased serum corticosterone (SCS) as an indicator of NIC withdrawal, as it is a quantitative indicator of naloxone (opioid receptor antagonist, NLX)-precipitated morphine withdrawal in mice. In this study, NLX precipitated an SCS increase in mice receiving repeated NIC, by a dose-dependent mechanism, and correlated with the dose and number of days of repeated NIC administration. When an opioid receptor antagonist (naltrexone) was concomitantly administered with repeated NIC, the NLX-precipitated SCS increase was not elicited. Concomitant administration of the α7 nicotinic acetylcholine receptor (nAChR) antagonist (methyllycaconitine) with repeated NIC, but not the α4β2 nAChR antagonist (dihydro-β-erythroidine), did not elicit an SCS increase by NLX. Thus, a physical dependence on NIC was in part mediated by the activation of the endogenous opioid system, located downstream of α7 nAChR.
authors.affiliation: Department of Pharmacology, Wakayama Medical University School of Medicine, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueno
authors.forename: Norikazu
authors.initials: N
authors.lastname: Kiguchi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Saika
authors.forename: Naoki
authors.initials: N
authors.lastname: Wakida
authors.forename: Chizuko
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Takehiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ozaki
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists; D009538:Nicotine / Q000008:administration & dosage*; D018847:Opioid Peptides / Q000235:genetics* / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000175:diagnosis; D014029:Tobacco Use Disorder / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D015415:Biomarkers; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D009270:Naloxone; D009538:Nicotine; D003345:Corticosterone; D000157:Aconitine