D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD
The mechanisms underlying the effects of psychostimulants in attention deficit hyperactivity disorder (ADHD) are not well understood, but indirect evidence implicates D2 dopamine receptors. Here we dissect the components of dopaminergic neurotransmission in the hyperactive mouse mutant coloboma to i...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2007-04-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610600324X |
| _version_ | 1819119869964058624 |
|---|---|
| author | Xueliang Fan Ellen J. Hess |
| author_facet | Xueliang Fan Ellen J. Hess |
| author_sort | Xueliang Fan |
| collection | DOAJ |
| description | The mechanisms underlying the effects of psychostimulants in attention deficit hyperactivity disorder (ADHD) are not well understood, but indirect evidence implicates D2 dopamine receptors. Here we dissect the components of dopaminergic neurotransmission in the hyperactive mouse mutant coloboma to identify pre- and postsynaptic elements essential for the effects of amphetamine in these mice. Amphetamine treatment reduced locomotor activity in coloboma mice, but induced a robust increase in dopamine overflow suggesting that abnormal regulation of dopamine efflux does not account for the behavioral effect. However, the D2-like dopamine receptor antagonists haloperidol and raclopride, but not the D1-like dopamine receptor antagonist SCH23390, blocked the amphetamine-induced reduction in locomotor activity in coloboma mice, providing direct evidence that D2-like dopamine receptors mediate the effect of amphetamine in these mice. With the precedent established that it is possible to directly antagonize this response, this strategy should prove useful for identifying novel therapeutics in ADHD. |
| first_indexed | 2024-12-22T06:11:38Z |
| format | Article |
| id | doaj.art-c272a861633944ed93db84760876c848 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T06:11:38Z |
| publishDate | 2007-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-c272a861633944ed93db84760876c8482022-12-21T18:36:12ZengElsevierNeurobiology of Disease1095-953X2007-04-01261201211D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHDXueliang Fan0Ellen J. Hess1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Corresponding author. Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer, 6-181, Baltimore, MD 21287, USA. Fax: +1 410 502 6737.The mechanisms underlying the effects of psychostimulants in attention deficit hyperactivity disorder (ADHD) are not well understood, but indirect evidence implicates D2 dopamine receptors. Here we dissect the components of dopaminergic neurotransmission in the hyperactive mouse mutant coloboma to identify pre- and postsynaptic elements essential for the effects of amphetamine in these mice. Amphetamine treatment reduced locomotor activity in coloboma mice, but induced a robust increase in dopamine overflow suggesting that abnormal regulation of dopamine efflux does not account for the behavioral effect. However, the D2-like dopamine receptor antagonists haloperidol and raclopride, but not the D1-like dopamine receptor antagonist SCH23390, blocked the amphetamine-induced reduction in locomotor activity in coloboma mice, providing direct evidence that D2-like dopamine receptors mediate the effect of amphetamine in these mice. With the precedent established that it is possible to directly antagonize this response, this strategy should prove useful for identifying novel therapeutics in ADHD.http://www.sciencedirect.com/science/article/pii/S096999610600324XHyperactivityColobomaDopamine receptorAmphetamineADHDMicrodialysis |
| spellingShingle | Xueliang Fan Ellen J. Hess D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD Neurobiology of Disease Hyperactivity Coloboma Dopamine receptor Amphetamine ADHD Microdialysis |
| title | D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD |
| title_full | D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD |
| title_fullStr | D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD |
| title_full_unstemmed | D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD |
| title_short | D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD |
| title_sort | d2 like dopamine receptors mediate the response to amphetamine in a mouse model of adhd |
| topic | Hyperactivity Coloboma Dopamine receptor Amphetamine ADHD Microdialysis |
| url | http://www.sciencedirect.com/science/article/pii/S096999610600324X |
| work_keys_str_mv | AT xueliangfan d2likedopaminereceptorsmediatetheresponsetoamphetamineinamousemodelofadhd AT ellenjhess d2likedopaminereceptorsmediatetheresponsetoamphetamineinamousemodelofadhd |