title: Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.
abstract: OBJECTIVE
  Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory.
  
  
  METHODS
  Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory.
  
  
  RESULTS
  Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP.
  
  
  CONCLUSIONS
  These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.
authors.affiliation: Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, 1 University Rd., Tainan, 70101, Taiwan, ROC.
authors.forename: Tien You
authors.initials: TY
authors.lastname: Liao
authors.affiliation: Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, 1 University Rd., Tainan, 70101, Taiwan, ROC.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Tzeng
authors.affiliation: Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, 1 University Rd., Tainan, 70101, Taiwan, ROC.
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Health Psychology, Chang Jung Christian University, Tainan, 71101, Taiwan, ROC.
authors.forename: Chianfang G
authors.initials: CG
authors.lastname: Cherng
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan, 70101, Taiwan, ROC.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Psychology, National Cheng Kung University, Tainan, 70101, Taiwan, ROC.
authors.forename: Sherry S-J
authors.initials: SS
authors.lastname: Hu
authors.affiliation: Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, 1 University Rd., Tainan, 70101, Taiwan, ROC. lungyu@mail.ncku.edu.tw.|Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan, 70101, Taiwan, ROC. lungyu@mail.ncku.edu.tw.
authors.forename: Lung
authors.initials: L
authors.lastname: Yu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020813:Receptor, trkB / Q000378:metabolism
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; C085746:rottlerin; D020813:Receptor, trkB; D003042:Cocaine
keywords: BDNF; Cocaine; Conditioning; Drug memory; Methamphetamine; Rottlerin