Learning and memory after neonatal exposure to 3,4‐methylenedioxymethamphetamine (ecstasy) in rats: Interaction with exposure in adulthood

Abstract

This study determined whether developmental and adult 3,4-methylenedioxymethamphetamine (MDMA) exposures in rats have interactive effects on body temperature, learning, other behaviors, and monoamine concentrations in the hippocampus, prefrontal cortex, and striatum. Learning was assessed in the Cincinnati water maze (CWM), Morris water maze (MWM), and novel object recognition (NOR). On acquisition trials in the MWM, significant differences from developmental MDMA exposure were found on latency, cumulative distance, path length, and angle of first bearing to the goal, but the early and adult MDMA exposure group performed no worse than the developmental-only MDMA group. In the reversal trials, however, an interaction was seen: latency to the goal, cumulative distance, and angle of first bearing were increased in animals treated both developmentally and in adulthood with MDMA compared with those treated only developmentally. Other tests (elevated zero maze, CWM, NOR, and open-field activity) did not show an interaction, nor did hippocampal concentrations of serotonin or dopamine. However, several behavioral tests showed neonatal MDMA effects, including increased errors in the CWM, reduced time spent with a new object in the NOR test, and reduced locomotor activity in the open-field. By contrast, adult MDMA decreased the number of entries into open quadrants of the elevated zero maze. Litter effects were controlled by treating litter as the experimental unit and using mixed models repeated measures analyses. Correlational analyses suggested that the MWM reversal interaction involves multiple monoamine changes. The results indicate that developmental MDMA exposure can interact with adult exposure to interfere with some aspects of learning.

Alterations in Body Temperature, Corticosterone, and Behavior Following the Administration of 5-Methoxy-Diisopropyltryptamine (‘Foxy’) to Adult Rats: a New Drug of Abuse

“…All tests were performed during the light phase of the light/dark cycle. This order of testing closely follows one that we have used to assess the impact of a single day exposure to other psychostimulants in adult animals (Cohen et al, 2005;Skelton et al, 2004;Williams et al, 2002). We have previously shown that the order of the CWM and MWM does not significantly affect the outcome with these compounds (Williams et al, 2002).…”

“…5-MEO-DIPT or SAL was administered four times at 2-h intervals on a single day (ie, the entire dosing period was 6 h from first to last dose). The multiple dose regimen is consistent with drug administration paradigms for other psychostimulants (Cappon et al, 1997;Cohen et al, 2005;Farfel and Seiden, 1995;O'Callaghan and Miller, 2002;O'Dell and Marshall, 2002). Injections were applied subcutaneously in the dorsum and the injection sites were varied to prevent irritation to the dermis, although some minor irritation was observed.…”

“…In order to monitor body temperature during drug administration, the animals were injected with implantable temperature transponders (IPTT-200; BMDS, Seaford, DE), Effects of 5-MEO-DIPT MT Williams et al as described previously (Cohen et al, 2005;Skelton et al, 2004;Williams et al, 2002). Temperature transponders were implanted under isoflourane anesthesia 3 days before the experiment.…”

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

“…Periadolescent MDMA treatments diminished the time spent exploring the objects, a gross index of attentional behavior [118], and decreased the discrimination ratio in this paradigm [119]. Neonatal MDMA (PD 11-20) diminished water maze learning and novel object exploration in adult-rats [27]. However, MDMA administration at earlier postnatal periods did not alter these endpoints [11,120].…”

“…The behavioral effects of MDMA (Table 2) are not limited to the period immediately after drug exposure as changes have also been documented weeks to months after MDMA [16,17,[24][25][26][27]92,93,118,119,155,159,166,168].…”