title: Nitric oxide in central amygdala potentiates expression of conditioned withdrawal induced by morphine.
abstract: OBJECTIVE
  The aim of this study was to evaluate if nitric oxide (NO) in the central amygdala (CeA) is involved in the expression of withdrawal aspects induced by morphine.
  
  
  METHODS
  Male Wistar rats (weighing 200-250 g) were bilaterally cannulated in the CeA and conditioned to morphine using an unbiased paradigm. Morphine (2.5-10 mg/kg) was subcutaneously injected once a day throughout the conditioning phase of the procedure. This phase also included 3-saline paired sessions. Naloxone (0.1-0.4 mg/kg, intraperitoneally [i.p.]), an antagonist of opioid receptors, was administered i.p. 10 min prior to testing of morphine-induced withdrawal features. The NO precursor, L-arginine (0.3-3 μg/rat) was intra-CeA injected prior to testing of naloxone response. To evaluate the involvement of NO system an inhibitor of NO synthase (NOS), N(G)-nitro-L-arginine methyl ester (L-NAME) (0.3-3 μg/rat), was injected ahead of L-arginine. Control group received saline solely instead of drug. As a complementary study, the activation of NOS was studied by nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d).
  
  
  RESULTS
  Morphine induced a significant increase in wet dog shaking and grooming behaviors compared with controls. Injection of naloxone pre-testing of morphine response significantly reversed the response to morphine. However, pre-microinjection of L-arginine intra-CeA recovered the response to morphine. Injection of L-NAME intra-CeA ahead of L-arginine though had no effect behaviorally, but, inhibited the NOS which has been evidenced by NADPH-d.
  
  
  CONCLUSIONS
  The present study shows that NO in the CeA potentiates the expression of conditioned withdrawal induced by morphine paired with naloxone.
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran ; Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran.
authors.forename: Manizheh
authors.initials: M
authors.lastname: Karami
authors.affiliation: Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Rahimpour
authors.affiliation: Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Karimi
authors.affiliation: Department of Physiology, Baghiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Hedayat
authors.initials: H
authors.lastname: Sahraei
mesh_terms: D000679:Amygdala / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D009292:Narcotic Antagonists; D009569:Nitric Oxide; D009270:Naloxone; D009020:Morphine; D019001:Nitric Oxide Synthase
keywords: Central amygdala; morphine; naloxone; nitric oxide; withdrawal behavior