title: Maternal separation affects dopamine transporter function in the spontaneously hypertensive rat: an in vivo electrochemical study.
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.
authors: Department of Human Biology, University of Cape Town, Observatory 7925 South Africa. jacqueline.womersley@gmail.com
authors: Jacqueline S
authors: JS
authors: Womersley
authors: Jennifer H
authors: JH
authors: Hsieh
authors: Lauriston A
authors: LA
authors: Kellaway
authors: Greg A
authors: GA
authors: Gerhardt
authors: Vivienne A
authors: VA
authors: Russell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism / Q000523:psychology; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000502:physiology*; D055664:Electrochemical Techniques; D005260:Female; D006973:Hypertension / Q000378:metabolism* / Q000523:psychology; D008297:Male; D008426:Maternal Deprivation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D004298:Dopamine