title: MK-801-induced behavioural sensitisation alters dopamine release and turnover in rat prefrontal cortex.
abstract: BACKGROUND
  Repeated exposure to psychostimulants that either increase dopamine (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce behavioural sensitisation, a phenomenon that may be important for the processes of addiction and even psychosis. A critical component of behavioural sensitisation is an increase in DA release within mesocorticolimbic circuits. In particular, sensitisation to amphetamine leads to increased DA release within well-known sub-cortical brain regions and also regulatory regions such as prefrontal cortex (PFC). However, it is unknown how DA release within the PFC of animals is altered by sensitisation to NMDA receptor antagonists.
  
  
  OBJECTIVE
  The aims of the present study were twofold, firstly to examine whether a single dose of dizocilpine maleate (MK-801) could induce long-term behavioural sensitisation and secondly to examine DA release in the PFC of sensitised rats.
  
  
  METHODS
  Behavioural sensitisation was assessed by measuring locomotion after drug exposure. DA release in the PFC was measured using freely moving microdialysis.
  
  
  RESULTS
  We show that a single dose of MK-801 can induce sensitisation to subsequent MK-801 exposure in a high percentage of rats (66 %). Furthermore, rats sensitised to MK-801 have altered DA release and turnover in the PFC compared with non-sensitised rats.
  
  
  CONCLUSIONS
  Schizophrenia patients have been postulated to have 'endogenous sensitisation' to psychostimulants. MK-801-induced sensitised rats, in particular when compared with non-sensitised rats, provide a useful model for studying PFC dysfunction in schizophrenia.
authors: Queensland Brain Institute, University of Queensland, Brisbane, QLD, 4072, Australia.
authors: Xiaoying
authors: X
authors: Cui
authors: Emilia
authors: E
authors: Lefevre
authors: Karly M
authors: KM
authors: Turner
authors: Carlos M
authors: CM
authors: Coelho
authors: Suzy
authors: S
authors: Alexander
authors: Thomas H J
authors: TH
authors: Burne
authors: Darryl W
authors: DW
authors: Eyles
mesh_terms: D000818:Animals; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D004298:Dopamine