The Open UniversitySkip to content
 

Repeated intermittent oral amphetamine administration results in locomotor tolerance not sensitization

Turner, Amy C.; Stramek, Agata; Kraev, Igor; Stewart, Michael G.; Overton, Paul G. and Dommett, Eleanor J. (2018). Repeated intermittent oral amphetamine administration results in locomotor tolerance not sensitization. Journal of Psychopharmacology, 32(8) pp. 949–954.

Full text available as:
[img]
Preview
PDF (Accepted Manuscript) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (310kB) | Preview
DOI (Digital Object Identifier) Link: https://doi.org/10.1177/0269881118763984
Google Scholar: Look up in Google Scholar

Abstract

Background: The phenomenon of locomotor sensitization to injected amphetamine is well-characterised. The increased locomotor activity found acutely is enhanced with repeated intermittent treatment. This effect arises due to hypersensitization of the dopaminergic system and is linked to drug addiction. A clinical population exposed to chronic repeated intermittent amphetamine treatment, such as is found for attention deficit hyperactivity disorder (ADHD), may be expected to be more at risk of addiction following this treatment. However, evidence suggests the opposite may be true. This suggests the route of administration may determine the direction of effects.

Aims and methods: We aimed to establish how an oral amphetamine treatment regimen, similar to that used in ADHD, impacts on locomotor activity, specifically whether tolerance or sensitization would arise. Healthy hooded Lister rats were given amphetamine (2 mg/kg, 5 mg/kg and 10 mg/kg) or a vehicle solution once daily for 4 weeks with a 5 day on, 2 day off schedule. Locomotor activity was measured on the first day of treatment to establish the acute effects and on the final day of treatment to examine the chronic effects.

Results: As expected, acute doses of amphetamine increased locomotor activity, although this only reached statistical significance for the 5 mg/kg and 10 mg/kg doses. By contrast, after chronic treatment, animals administered these doses showed reduced activity indicating drug tolerance rather than sensitization had occurred.

Conclusion: We suggest that the route of administration used in ADHD, which results in more stable and longer duration drug levels in the blood, results in tolerance rather than sensitization and that this effect could explain the reduced likelihood of substance addiction in those treated with psychostimulants for ADHD.

Item Type: Journal Item
Copyright Holders: 2018 The Authors
ISSN: 1461-7285
Keywords: Amphetamine; locomotor sensitization; tolerance; attention deficit hyperactivity disorder
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 54092
SWORD Depositor: Jisc Publications-Router
Depositing User: Jisc Publications-Router
Date Deposited: 03 Apr 2018 14:08
Last Modified: 22 May 2019 02:22
URI: http://oro.open.ac.uk/id/eprint/54092
Share this page:

Metrics

Altmetrics from Altmetric

Citations from Dimensions

Download history for this item

These details should be considered as only a guide to the number of downloads performed manually. Algorithmic methods have been applied in an attempt to remove automated downloads from the displayed statistics but no guarantee can be made as to the accuracy of the figures.

Actions (login may be required)

Policies | Disclaimer

© The Open University   contact the OU