Elsevier

Biological Psychiatry

Volume 59, Issue 12, 15 June 2006, Pages 1219-1226
Biological Psychiatry

Original article
3,4-Methylenedioxymethamphetamine in Adult Rats Produces Deficits in Path Integration and Spatial Reference Memory

https://doi.org/10.1016/j.biopsych.2005.09.006Get rights and content

Background

±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that causes cognitive deficits in humans. A rat model for learning and memory deficits has not been established, although some cognitive deficits have been reported.

Methods

Male Sprague-Dawley rats were treated with MDMA (15 mg/kg x 4 doses) or saline (SAL) (n = 20/treatment group) and tested in different learning paradigms: 1) path integration in the Cincinnati water maze (CWM), 2) spatial learning in the Morris water maze (MWM), and 3) novel object recognition (NOR). One week after drug administration, testing began in the CWM, then four phases of MWM, and finally NOR. Following behavioral testing, monoamine levels were assessed.

Results

±3,4-Methylenedioxymethamphetamine-treated rats committed more CWM errors than did SAL-treated rats. ±3,4-Methylenedioxymethamphetamine-treated animals were further from the former platform position during each 30-second MWM probe trial but showed no differences during learning trials with the platform present. There were no group differences in NOR. ±3,4-Methylenedioxymethamphetamine depleted serotonin in all brain regions and dopamine in the striatum.

Conclusions

±3,4-Methylenedioxymethamphetamine produced MWM reference memory deficits even after complex learning in the CWM, where deficits in path integration learning occurred. Assessment of path integration may provide a sensitive index of MDMA-induced learning deficits.

Section snippets

Subjects

Male Sprague-Dawley rats (225–250 g) were obtained from Charles River Laboratories (Raleigh, North Carolina). The rats were allowed to acclimate to the colony room for 1 week prior to the day of drug administration. The colony room was maintained at a temperature of 21°C to 22°C with food and water available ad libitum. The animals were initially housed in pairs in cages measuring 45.7 x 23.8 x 20.3 cm prior to drug administration, then singly during and following drug administration. For the

Temperature Monitoring

Both the SAL- and MDMA-treated animals began the experiment with comparable body temperatures. There was a significant main effect of treatment, F(1,34) = 43.11, p < .0001; time, F(20,680) = 5.89, p < .0001; and the interaction of treatment x time, F(20,680) = 15.89, p < .0001. Analysis of the interaction showed that following the first injection, body temperatures of the MDMA-treated animals steadily increased, and at 90 minutes, temperatures were significantly increased relative to

Discussion

The major new finding within this set of experiments was that MDMA-treated animals committed more errors in the CWM than control subjects. Cincinnati water maze requires a path integration strategy for finding the goal, as opposed to the MWM, where an animal relies on the use of spatial cues to navigate through its environment (Morris et al 1982). Path integration involves the use of both allothetic (external) and idiothetic (internal) cues (Whishaw et al 2001). Idiothetic cues may be visual,

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