title: Exposure pattern influences the degree of drug-seeking behaviour after withdrawal.
abstract: OBJECTIVE
  The occurrence of a relapse during abstinence is an important issue that must be addressed during treatment for drug addiction. We investigated the influence of drug exposure pattern on morphine-seeking behaviour following withdrawal. We also studied the role of the hippocampus in this process to confirm its involvement in drug relapse.
  
  
  METHODS
  Male Sprague-Dawley rats that were trained to self-administer morphine (1.0 mg/kg) using 2, 4, 6, 8, or 10 h daily sessions underwent withdrawal in their home cages and were re-exposed to the operant chamber to evaluate morphine-seeking behaviour. During the relapse session, rats were intravenously injected with morphine (0.25 mg/kg) or saline before re-exposure to the chamber. In the second experiment, rats were administered a microinjection of saline or cobalt chloride (CoCl2, 1 mM), a synaptic blocker, into the CA1 of the hippocampus prior to the relapse test.
  
  
  RESULTS
  In the first experiment, more morphine-seeking behaviour was observed in the 2 h group (animals trained to self-administer morphine during a 2 h daily session spread over 21 days) during the relapse session, despite all groups being exposed to similar amounts of morphine during the training period before withdrawal. In the second experiment, pretreatment with CoCl2 markedly reduced morphine-seeking behaviour in the 2 h group.
  
  
  CONCLUSIONS
  The present findings suggest that the exposure pattern influences the degree of relapse and that control of memorisation is important for prevention of relapse.
authors.affiliation: 1Department of Acupuncture, Moxibustion and Acupoint,College of Korean Medicine,Daegu Haany University,Daegu,South Korea.
authors.forename: Sunghyun
authors.initials: S
authors.lastname: In
authors.affiliation: 2Department of Pharmacology,Mudanjiang Medical University,Mudanjiang,China.
authors.forename: Rong Jie
authors.initials: RJ
authors.lastname: Zhao
authors.affiliation: 1Department of Acupuncture, Moxibustion and Acupoint,College of Korean Medicine,Daegu Haany University,Daegu,South Korea.
authors.forename: Hye Ryeong
authors.initials: HR
authors.lastname: Han
authors.affiliation: 3Department of Physiology,College of Korean Medicine,Daegu Haany University,Daegu,South Korea.
authors.forename: Chae Ha
authors.initials: CH
authors.lastname: Yang
authors.affiliation: 3Department of Physiology,College of Korean Medicine,Daegu Haany University,Daegu,South Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: 3Department of Physiology,College of Korean Medicine,Daegu Haany University,Daegu,South Korea.
authors.forename: Young S
authors.initials: YS
authors.lastname: Gwak
authors.affiliation: 1Department of Acupuncture, Moxibustion and Acupoint,College of Korean Medicine,Daegu Haany University,Daegu,South Korea.
authors.forename: Bong Hyo
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000818:Animals; D003035:Cobalt / Q000008:administration & dosage*; D003216:Conditioning, Operant; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013375:Substance Withdrawal Syndrome
chemical_list: D003035:Cobalt; D009020:Morphine; C018021:cobaltous chloride
keywords: hippocampus; memory; morphine-seeking; relapse; withdrawal