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