title: In vivo neurochemical evidence that delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, inhibit acetylcholine efflux in the nucleus accumbens of freely moving rats.
abstract: Cholinergic neurons in the nucleus accumbens express delta- and mu-opioid receptors that are thought to inhibit neural activity. Delta- and mu-opioid receptors are divided into delta1- and delta2-opioid receptors and mu1- and mu2-opioid receptors, respectively. We analysed the roles of delta- and mu-opioid receptor subtypes in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. Other than naloxonazine, given intraperitoneally, delta- and mu-opioid receptor ligands were administered intracerebrally through the dialysis probe. Doses of these compounds indicate total amount (mol) over an infusion time of 30-60min. To monitor basal acetylcholine, a low concentration of physostigmine (50nM) was added to the perfusate. The delta1-opioid receptor agonist DPDPE (3 and 300pmol) and delta2-opioid receptor agonist deltorphin II (3 and 30pmol) decreased accumbal acetylcholine in a dose-related manner. DPDPE (300pmol)- and deltorphin II (3pmol)-induced reductions in acetylcholine were each inhibited by the delta1-opioid receptor antagonist BNTX (0.3pmol) and delta2-opioid receptor antagonist naltriben (15pmol), respectively. The mu-opioid receptor agonists endomorphin-1 and endomorphin-2 (6 and 30nmol) decreased acetylcholine in a dose-related manner. Endomorphin-1- and endomorphin-2 (30nmol)-induced reductions in acetylcholine were prevented by the mu-opioid receptor antagonist CTOP (3nmol). The mu1-opioid receptor antagonist naloxonazine (15mg/kg ip), which inhibits endomorphin-1 (15nmol)-induced accumbal dopamine efflux, did not alter endomorphin-1- or endomorphin-2 (30nmol)-induced reductions in acetylcholine efflux. This study provides in vivo evidence for delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, that inhibit accumbal cholinergic neural activity.
authors.affiliation: Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kiguchi
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Aono
authors.affiliation: Department of Oral surgery, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Yamamoto-Nemoto
authors.affiliation: Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kosuge
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
authors.forename: John L
authors.initials: JL
authors.lastname: Waddington
authors.affiliation: Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ishige
authors.affiliation: Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan. Electronic address: saigusa.tadashi@nihon-u.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Saigusa
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009068:Movement; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D000109:Acetylcholine; D004298:Dopamine
keywords: Acetylcholine; Delta-opioid receptor; Dopamine; Microdialysis; Mu-opioid receptor; Nucleus accumbens