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

Cui, Xiaoying, Lefevre, Emilia, Turner, Karly M., Coelho, Carlos M., Alexander, Suzy, Burne, Thomas H. J. and Eyles, Darryl W. (2014) MK-801-induced behavioural sensitisation alters dopamine release and turnover in rat prefrontal cortex. Psychopharmacology, 232 3: 509-517. doi:10.1007/s00213-014-3689-9


Author Cui, Xiaoying
Lefevre, Emilia
Turner, Karly M.
Coelho, Carlos M.
Alexander, Suzy
Burne, Thomas H. J.
Eyles, Darryl W.
Title MK-801-induced behavioural sensitisation alters dopamine release and turnover in rat prefrontal cortex
Journal name Psychopharmacology   Check publisher's open access policy
ISSN 0033-3158
1432-2072
Publication date 2014-07-29
Year available 2014
Sub-type Article (original research)
DOI 10.1007/s00213-014-3689-9
Open Access Status Not yet assessed
Volume 232
Issue 3
Start page 509
End page 517
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract 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.
Formatted 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.
Keyword MK-801
Behavioural sensitisation
Prefrontal cortex
Dopamine
Microdialysis
Schizophrenia
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP 1024239
Institutional Status UQ
Additional Notes Published online ahead of print 29 July 2014.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 4 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 21 Oct 2014, 10:59:39 EST by System User on behalf of Queensland Brain Institute