MK-801-induced behavioural sensitisation alters dopamine release and turnover in rat prefrontal cortex

Xiaoying Cui, Emilia Lefevre, Karly M. Turner, Carlos M. Coelho, Suzy Alexander, Thomas H.J. Burne, Darryl W. Eyles

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: 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. Objectives: 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. Materials and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)509-517
Number of pages9
JournalPsychopharmacology
Volume232
Issue number3
DOIs
StatePublished - Feb 2015
Externally publishedYes

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Health and Medical Research Council (APP 1024239). None of the authors had any financial relationship with the organisation that sponsored the research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Health and Medical Research Council.

Publisher Copyright:
© 2014 Springer-Verlag Berlin Heidelberg.

Keywords

  • Behavioural sensitisation
  • Dopamine
  • Microdialysis
  • MK-801
  • Prefrontal cortex
  • Schizophrenia

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