title: Galantamine attenuates the heroin seeking behaviors induced by cues after prolonged withdrawal in rats.
abstract: OBJECTIVE
  Evidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues.
  
  
  METHODS
  Rats were trained to self-administer heroin for 12 days, underwent extinction training for 12 days followed by two weeks in their home cages. Then the conditioned cues were introduced for the reinstatement of heroin-seeking.
  
  
  RESULTS
  The reinstatement of heroin-seeking induced by cues was attenuated by the administration of galantamine (0, 0.3, 1 or 3mg/kg, i.p.) in a dose-dependent manner. In contrast, galantamine only at the dose of 3mg/kg could inhibit the reinstatement of sucrose-seeking. Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats. The inhibition of drug-seeking by galantamine was reversed by pretreatment with scopolamine (0.5mg/kg) but not with mecamylamine (3mg/kg) or scopolamine methobromide (1mg/kg). Moreover, the microinjection of galantamine into the LDT blocked cue-induced heroin-seeking, while the microinjection of scopolamine into the LDT reversed the inhibitory effect of galantamine on drug-seeking behavior.
  
  
  CONCLUSIONS
  The results suggest that cholinergic transmission in the LDT may play a critical role in heroin-seeking behavior induced by cues and that galantamine may have the beneficial effect of blocking heroin-seeking behavior, which is mediated through its actions on the muscarinic receptors.
authors.affiliation: Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, 42 Xibei Str., Ningbo 315010, PR China.
authors.forename: Huifen
authors.initials: H
authors.lastname: Liu
authors.forename: Miaojun
authors.initials: M
authors.lastname: Lai
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Anna
authors.initials: A
authors.lastname: Sun
authors.forename: Baomiao
authors.initials: B
authors.lastname: Ma
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Zhang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005702:Galantamine / Q000494:pharmacology*; D003932:Heroin / Q000008:administration & dosage / Q000009:adverse effects*; D008464:Mecamylamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D017557:Ventral Tegmental Area / Q000187:drug effects
chemical_list: D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D009294:Narcotics; D005702:Galantamine; D008464:Mecamylamine; D003932:Heroin; D012601:Scopolamine