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Maternal separation affects dopamine transporter function in the spontaneously hypertensive rat: an in vivo electrochemical study.

Womersley JS, Hsieh JH, Kellaway LA, Gerhardt GA, Russell VA - Behav Brain Funct (2011)

Bottom Line: SHR entered the inner zone more frequently and covered a significantly greater distance than WKY.These results suggest that the chronic mild stress of maternal separation impaired the function of striatal DAT in SHR.The present findings suggest that maternal separation failed to alter the behaviour of SHR in the open field and elevated plus maze.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Biology, University of Cape Town, Observatory 7925 South Africa. jacqueline.womersley@gmail.com

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.

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Representative graph showing dopamine clearance in rat striatum. The amplitude of the peak was measured as the maximum change in dopamine concentration from baseline. T100 represents the time taken for the dopamine concentration to return from maximum amplitude to baseline. The k-1 is the first order rate constant. It provides a measure of the rate of decay of dopamine concentration over time, to provide a measure of DAT efficiency.
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Figure 1: Representative graph showing dopamine clearance in rat striatum. The amplitude of the peak was measured as the maximum change in dopamine concentration from baseline. T100 represents the time taken for the dopamine concentration to return from maximum amplitude to baseline. The k-1 is the first order rate constant. It provides a measure of the rate of decay of dopamine concentration over time, to provide a measure of DAT efficiency.

Mentions: The amplitude, defined as the difference between baseline and peak dopamine concentration, first-order rate constant (k-1), and clearance time (T100) were measured (Figure 1). The first-order rate constant k-1 is calculated from the decay of dopamine concentration versus time. It is indicative of dopamine uptake efficiency and as such, is indirectly proportional to the clearance time [51,52]. T100 represents the time taken for the dopamine concentration to return from peak amplitude to the baseline value prior to the ejection of dopamine. Independent recordings of dopamine clearance were made at 0.5 mm intervals (between 3.5 and 5 mm ventral to the cortical surface) in the striatum. A total of 38 recordings were obtained from 10 non-separated WKY (WKY NMS), 24 recordings from 7 maternally separated WKY (WKY MS), 25 recordings from 7 non-separated SHR (SHR NMS) and 31 recordings from 8 maternally separated SHR (SHR MS).


Maternal separation affects dopamine transporter function in the spontaneously hypertensive rat: an in vivo electrochemical study.

Womersley JS, Hsieh JH, Kellaway LA, Gerhardt GA, Russell VA - Behav Brain Funct (2011)

Representative graph showing dopamine clearance in rat striatum. The amplitude of the peak was measured as the maximum change in dopamine concentration from baseline. T100 represents the time taken for the dopamine concentration to return from maximum amplitude to baseline. The k-1 is the first order rate constant. It provides a measure of the rate of decay of dopamine concentration over time, to provide a measure of DAT efficiency.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285054&req=5

Figure 1: Representative graph showing dopamine clearance in rat striatum. The amplitude of the peak was measured as the maximum change in dopamine concentration from baseline. T100 represents the time taken for the dopamine concentration to return from maximum amplitude to baseline. The k-1 is the first order rate constant. It provides a measure of the rate of decay of dopamine concentration over time, to provide a measure of DAT efficiency.
Mentions: The amplitude, defined as the difference between baseline and peak dopamine concentration, first-order rate constant (k-1), and clearance time (T100) were measured (Figure 1). The first-order rate constant k-1 is calculated from the decay of dopamine concentration versus time. It is indicative of dopamine uptake efficiency and as such, is indirectly proportional to the clearance time [51,52]. T100 represents the time taken for the dopamine concentration to return from peak amplitude to the baseline value prior to the ejection of dopamine. Independent recordings of dopamine clearance were made at 0.5 mm intervals (between 3.5 and 5 mm ventral to the cortical surface) in the striatum. A total of 38 recordings were obtained from 10 non-separated WKY (WKY NMS), 24 recordings from 7 maternally separated WKY (WKY MS), 25 recordings from 7 non-separated SHR (SHR NMS) and 31 recordings from 8 maternally separated SHR (SHR MS).

Bottom Line: SHR entered the inner zone more frequently and covered a significantly greater distance than WKY.These results suggest that the chronic mild stress of maternal separation impaired the function of striatal DAT in SHR.The present findings suggest that maternal separation failed to alter the behaviour of SHR in the open field and elevated plus maze.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Human Biology, University of Cape Town, Observatory 7925 South Africa. jacqueline.womersley@gmail.com

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.

Show MeSH
Related in: MedlinePlus