(+/–)3,4-Methylenedioxymethamphetamine (MDMA) Dose-Dependently Impairs Spatial Learning in the Morris Water Maze after Exposure of Rats to Different Five-Day Intervals from Birth to Postnatal Day TwentyVorhees C.V. · Schaefer T.L. · Skelton M.R. · Grace C.E. · Herring N.R. · Williams M.T.
Division of Neurology, Department of Pediatrics and Cincinnati Children’s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
During postnatal days (PD) 11–20, (+/–)3,4-methylenedioxymethamphetamine (MDMA) treatment impairs egocentric and allocentric learning, and reduces spontaneous locomotor activity; however, it does not have these effects during PD 1–10. How the learning impairments relate to the stress hyporesponsive period (SHRP) is unknown. To test this association, the preweaning period was subdivided into 5-day periods from PD 1–20. Separate pups within each litter were injected subcutaneously with 0, 10, 15, 20, or 25 mg/kg MDMA ×4/day on PD 1–5, 6–10, 11–15, or 16–20, and tested as adults. The 3 highest MDMA dose groups showed reduced locomotor activity during the first 10 min (of 60 min), especially in the PD 1–5 and 6–10 dosing regimens. MDMA groups in all dosing regimens showed impaired allocentric learning in the Morris water maze (on acquisition and reversal, all MDMA groups were affected; on the small platform phase, the 2 high-dose groups were affected). No effects of MDMA were found on anxiety (elevated zero maze), novel object recognition, or egocentric learning (although a nonsignificant trend was observed). The Morris maze results did not support the idea that the SHRP is critical to the effects of MDMA on allocentric learning. However, since no effects on egocentric learning were found, but were apparent after PD 11–20 treatment, the results show that these 2 forms of learning have different exposure-duration sensitivities.
© 2009 S. Karger AG, Basel
Charles V. Vorhees
Division of Neurology (MLC 7044)
Cincinnati Children’s Research Foundation, 3333 Burnet Ave.
Cincinnati, OH 45229-3039 (USA)
Tel. +1 513 636 8622, Fax +1 513 636 3912, E-Mail firstname.lastname@example.org
Received: March 25, 2008
Accepted after revision: August 7, 2008
Published online: April 17, 2009
Number of Print Pages : 14
Number of Figures : 5, Number of Tables : 3, Number of References : 46
Vol. 31, No. 1-2, Year 2009 (Cover Date: April 2009)
Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)
For additional information: http://www.karger.com/DNE