title: Context- and time-dependent neurobiological and behavioral sensitization induced by a single morphine exposure in mice.
abstract: BACKGROUND
  Drug-induced sensitization in the mesocorticolimbic systems is thought to play an important role in certain aspects of drug addiction, including the involvement of drug-associated cues and environments in mediating drug-seeking behaviors. Our previous studies have identified the significance of heat shock protein 70 (Hsp70) in the development of a single morphine exposure-induced behavioral sensitization.
  
  
  OBJECTIVE
  The present study expands upon these findings by investigating the effect of environment on the expression of behavioral sensitization induced by a single morphine exposure, and the potential involvement of Hsp70 protein levels in these effects.
  
  
  METHODS
  Mice were pretreated with a single morphine injection in test chambers (morphine-paired) or home cages (morphine-unpaired) on day 1 and challenged on day 2 or 8, in test chambers. Hsp70 expression in the nucleus accumbens (NAc) was analyzed after the challenge.
  
  
  RESULTS
  The expression of single morphine exposure-induced behavioral sensitization was accompanied by a significant increase in Hsp70 expression in NAc. In contrast, the unpaired morphine-treated group failed to exhibit behavioral sensitization or higher Hsp70 expression. Additionally, by adding a habituation process prior to the challenge, we demonstrated that conditioned hyperactivity, which was not accompanied by an increased expression of Hsp70, is not essential for behavioral sensitization.
  
  
  CONCLUSIONS
  Behavioral sensitization induced by a single morphine exposure in mice exhibits context and time dependency, with environmental context likely functioning via an inhibitory conditioning mechanism. Furthermore, alterations in Hsp70 expression in the NAc may represent a neurobiological sensitization mechanism mediating context- and time-dependent behavioral sensitization.
authors.affiliation: Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Wang-Jun
authors.initials: WJ
authors.lastname: Qin
authors.affiliation: Department of Pharmacy, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Peng-Mei
authors.initials: PM
authors.lastname: Li
authors.affiliation: Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Jun-Xu
authors.initials: JX
authors.lastname: Li
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Noori
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Rick E
authors.initials: RE
authors.lastname: Bernardi
authors.affiliation: Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing, 100191, China. liangjh@bjmu.edu.cn.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Liang
authors.affiliation: Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China. lpandwpandmemory@126.com.
authors.forename: Xiang-Lin
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006948:Hyperkinesis / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D050884:HSP72 Heat-Shock Proteins; D009020:Morphine
keywords: Behavioral sensitization; Context-dependent; Heat shock protein 70; Morphine; Neurobiological sensitization