(+/–)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 Twenty

Treating rat pups with MDMA during different preweaning periods (postnatal days 1–5, 6–10, 11–15, or 16–20) produced lasting effects. The three highest doses (15, 20, and 25 mg/kg) reduced spontaneous locomotor activity during the first 10 minutes of testing, especially when given on days 1–5 or 6–10. All MDMA-treated groups showed impaired allocentric learning in the Morris water maze during both acquisition and reversal phases; the two highest doses also impaired performance on the small platform phase. No effects were found on anxiety, novel object recognition, or egocentric learning, though a nonsignificant trend appeared. The results indicate that allocentric and egocentric learning have different exposure-duration sensitivities and that the stress hyporesponsive period is not critical for MDMA's effects on allocentric learning.

Study at a glance

Abstract

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.