Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study

Jacqueline S. Womersley, Jennifer H. Hsieh, Lauriston A. Kellaway, Greg A. Gerhardt, Vivienne A. Russell

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30 Scopus citations

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR from control rat strains.Methods: SHR and control Wistar-Kyoto (WKY) rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function.Results: Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k -1) in SHR striatum. Consistent with this observation, the dopamine clearance time (T100) was increased in SHR. These results suggest that the chronic mild stress of maternal separation impaired the function of striatal DAT in SHR.Conclusions: The present findings suggest that maternal separation failed to alter the behaviour of SHR in the open field and elevated plus maze. However, maternal separation altered the dopaminergic system by decreasing surface expression of DAT and/or the affinity of DAT for dopamine, increasing the time to clear dopamine from the extracellular fluid in the striatum of SHR.

Original languageEnglish
Article number49
JournalBehavioral and Brain Functions
Volume7
DOIs
StatePublished - Dec 1 2011

Bibliographical note

Funding Information:
The authors wish to acknowledge the support of the University of Cape Town, the Medical Research Council of South Africa (MRC), the National Research Foundation (NRF) and the National Institutes of Health (NIH) Fogarty International Center grant R01TW008040 to Michael J. Zigmond, principal investigator. The authors would also like to thank Mr Charles Harris for design and construction of essential equipment and Ms Nuraan Ismail and Mr Buyisile Dingalibala for assistance with animal care. Any opinion, findings and conclusions, or recommendations expressed in this material are those of the authors and therefore the NRF does not accept any liability in regard thereto.

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Biological Psychiatry
  • Behavioral Neuroscience

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