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ARTICLE

Recovery of Presynaptic Dopaminergic Functioning in Rats Treated with Neurotoxic Doses of Methamphetamine

Wayne A. Cass and Michael W. Manning
Journal of Neuroscience 1 September 1999, 19 (17) 7653-7660; https://doi.org/10.1523/JNEUROSCI.19-17-07653.1999
Wayne A. Cass
1Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536
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Michael W. Manning
1Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536
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    Fig. 1.

    A, Potassium-evoked overflow of DA in the striatum of a control rat. Potassium (125 nl, 70 mmK+) was applied at the arrowhead at time 0. The solid line shows the oxidation current response (Ox.), and the dashed line is the corresponding reduction current response (Red.). The reduction/oxidation current ratio (0.69) indicates that the predominate electroactive species detected was DA. The T20 and T60 time points used for calculating clearance rate are indicated on the oxidation curve. B, Illustration of the location of the recording sites for the in vivoelectrochemical recordings and the positioning of the microdialysis probe for the dialysis experiments. For the electrochemistry studies, data were collected at 0.5 mm steps throughout the dorsoventral extent of the striatum and nucleus accumbens (NAc) on one side of the brain (3.5–7.5 mm below the surface of the cortex). In vivo electrochemistry and in vivo microdialysis were performed on separate groups of rats. This diagram represents a coronal section of the forebrain ∼1.2 mm anterior to bregma.

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    Fig. 2.

    Summary of potassium-evoked DA signal amplitude throughout the striatum and nucleus accumbens of animals treated with saline or METH. Experiments were performed at 1 week, 1 month, 6 months, or 12 months after treatment with saline or METH, as indicated in the figure. The data shown are mean ± SEM values for eight animals per group. *p < 0.05 versus saline group at same depth (three-way repeated measures ANOVA followed by Newman–Keuls post hoc comparisons).

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    Fig. 3.

    Summary of DA clearance rate after potassium application throughout the striatum and nucleus accumbens of animals treated with saline or METH. Experiments were performed at 1 week, 1 month, 6 months, or 12 months after treatment with saline or METH, as indicated in the figure. The data shown are mean ± SEM values for eight animals per group. *p < 0.05 versus saline group at same depth (three-way repeated measures ANOVA followed by Newman–Keuls post hoc comparisons).

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    Fig. 4.

    Clearance of exogenous DA in the striatum of saline- and METH-treated animals at four time points after treatment. DA was applied by pressure ejection into the striatum (3.5–6.0 mm below the surface of the brain), and its clearance was monitored electrochemically. The amount of DA applied at each site was adjusted to achieve a signal of ∼3 μm in amplitude (top graph). The corresponding clearance rates for the resulting signals are shown in the bottom graph. The data from all sites in each animal were averaged together to get a single mean value per animal. The values shown are mean ± SEM for four animals per group. *p < 0.05 versus saline group at same time (two-way ANOVA followed by Newman–Keuls post hoccomparisons).

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    Fig. 5.

    Dialysate levels of DA from the striatum of awake rats treated 1 week, 1 month, 6 months, or 12 months earlier with saline or METH. Excess potassium (100 mm) was included in the perfusate for 20 min starting at 0 min (horizontal bar above K+ ), and 100 μm amphetamine was included in the perfusate for 20 min starting at 120 min (horizontal bar aboveAmphetamine). The values shown are mean ± SEM from six or seven animals in each group. *p < 0.05 versus saline at same time point (three-way repeated measures ANOVA followed by Newman–Keuls post hoc comparisons).

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    Fig. 6.

    Basal levels of dialysate DA, DOPAC, and HVA from the striatum of awake rats treated 1 week, 1 month, 6 months, or 12 months earlier with saline or METH. The data shown are mean values ± SEM from six or seven animals in each group. *p≤ 0.05 versus saline group at same time (two-way ANOVA followed by Newman–Keuls post hoc comparisons).

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    Table 1.

    Striatal levels of DA from animals treated with saline or METH

    TreatmentTime after treatment
    1 week1 month6 months12 months
    Saline13.74  ± 0.6614.06  ± 0.7713.52  ± 0.5813.81  ± 0.78
    METH6.39  ± 0.71*7.25  ± 0.61*10.84  ± 0.43*12.70  ± 0.77
    • Levels are expressed as micrograms per gram wet weight of tissue. Values are mean ± SEM for 14–15 animals per group.

    • *p < 0.05 versus saline group at same time point (two-way ANOVA followed by Newman–Keuls post hoccomparisons).

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The Journal of Neuroscience: 19 (17)
Journal of Neuroscience
Vol. 19, Issue 17
1 Sep 1999
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Recovery of Presynaptic Dopaminergic Functioning in Rats Treated with Neurotoxic Doses of Methamphetamine
Wayne A. Cass, Michael W. Manning
Journal of Neuroscience 1 September 1999, 19 (17) 7653-7660; DOI: 10.1523/JNEUROSCI.19-17-07653.1999

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Recovery of Presynaptic Dopaminergic Functioning in Rats Treated with Neurotoxic Doses of Methamphetamine
Wayne A. Cass, Michael W. Manning
Journal of Neuroscience 1 September 1999, 19 (17) 7653-7660; DOI: 10.1523/JNEUROSCI.19-17-07653.1999
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Keywords

  • methamphetamine
  • neurotoxicity
  • striatum
  • dopamine
  • in vivo electrochemistry
  • in vivomicrodialysis

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